Note: Descriptions are shown in the official language in which they were submitted.
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r
Title
HERBAL PRODUCT COMPRISING CINNAMON AND BITTER MELON
Field of the Invention
[0001] This invention relates to a new herbal product and in particular, to a
new herbal
product comprising cinnamon (Cinnamomi cassiae: Cinnamonum verum) and bitter
melon
(Momordica charantia). Each of these ingredients is known to demonstrate
therapeutic effects
but the combination of the two ingredients demonstrates significant synergism
and improved
therapeutic effects.
Background of the Invention
[0002] Diabetes, hyperlipidemis and obesity, besides being detrimental to
health by
themselves, are all recognized risk factors for cardiovascular disease (CVD),
which is still the
number one killer in North America. Obesity is reaching epidemic proportions
in N. America
and Type 2 diabetes, with its close links to obesity, has become a major cause
for concern. High
blood cholesterol levels have persisted as a key factor in the development of
atherosclerosis and
CVD, and high triglycerides have also been recognized as an important risk
factor, especially for
women. The incidence of metabolic syndrome (also known as insulin resistance
syndrome, or
syndrome X), which presents as a cluster of characteristics and symptoms,
including obesity,
increased waist circumference, borderline high blood glucose and blood
pressure levels, and
abnormal blood lipid levels, has been increasing sharply since it was first
recognised as a
common precursor to both CVD and diabetes.
[0003] While modern pharmaceutical drugs exist for the treatment of
hyperlipidemia,
diabetes, and CVD, the side effects associated with many of these drugs may
have severely
detrimental health effects which preclude their use, or these side effects may
simply reduces
patient compliance. As a result, a majority of the population has been looking
elsewhere for the
treatment of these diseases and conditions, and complementary therapies have
become a popular
alternative to the pharmaceutical model for treatment.
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[0004] Two herbal products which are likely candidates as treatment options
are bitter melon
(Momordica charantia) and cinnamon (Cinnamomi cassiae; Cinnamomum verum).
Bitter melon
has been used for its pharmaceutical properties since the 16th century, by
residents of tropical
areas of the world. It has recognized anti-viral, anti-bacterial, anti-cancer,
and
immunomodulatory properties; however, in recent years, most research focus has
been on the
glucose-lowering ability of bitter melon. In animal studies, bitter melon
supplementation of the
diets of diabetic animals has resulted in improved oral glucose tolerance, a
reduction in blood
glucose levels and reduced insulin resistance. Furthermore, bitter melon has
been observed to
decrease obesity, and modestly reduce cholesterol and triglyceride levels in
animal species.
[0005] Like bitter melon, cinnamon has been widely used for centuries, and is
a traditional
folk herb for diabetes mellitus in Russia, China and Korea. It is also thought
to possess anti-
fever and antibiotic properties, as well as being as mild analgesic and
sedative. Again, like bitter
melon, recent research has focused on its ability to lower blood glucose
levels. In recent animal
studies, its blood-glucose-lowering ability was dose-dependent, with higher
doses lowering
glucose levels more than lower doses. Insulin levels increased, as did HDL
cholesterol levels
(the so-called "good" cholesterol). Total and LDL cholesterol levels and
triglyceride levels, on
the other hand, were reduced with cinnamon supplementation. An additional
benefit of
cinnamon supplementation may be its antioxidant capacity, due to its phenolic
acids and
flavonoids. This antioxidant capacity may not only slow the progression of
Type 2 diabetes
complications, by quenching the excessive oxygen free radical damage seen in
diabetes, it may
also protect LDL cholesterol from oxidation, reducing the likelihood of it
being scavenged and
incorporated into blood vessel wall plaque, the latter being a major part of
atherosclerosis,
hypertension and CVD.
[0006] Thus far, human studies on either herb separately is extremely limited.
In animals,
although bitter melon and cinnamon have similar physiological effects - lower
blood glucose,
cholesterol and triglyceride levels - their mechanisms of action are
different.
[0007] Accordingly, the present inventors have combined these two basic
ingredients into a
single therapeutic formulation which demonstrates synergistic results. The
inventors have found
that the new therapeutic formulation has resulted in the following:
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1. Reduction in blood glucose levels and increased glucose tolerance in
diabetics and people
with metabolic syndrome.
2. Reduction in total and LDL cholesterol and triglycerides, and increase in
HDL cholesterol in
people with dyslipidemia, including people with metabolic syndrome.
3. Reduction in obesity.
4. Improved antioxidant capacity, with the potential to protect diabetics
against free radical
damage, and to reduce oxidized LDL cholesterol levels.
[0008] Thus, this new therapeutic formulation may be used to treat diabetes
and CVD, and
also in the precursor syndrome, where almost all of the characteristics of
this syndrome - high
total and LDL cholesterol, high triglyceride, low HDL cholesterol, borderline
high blood glucose
levels, obesity and high waist circumference - may be improved. Even
borderline high blood
pressure, which is normally affected by the degree of obesity, may be reduced.
In effect, this
therapeutic formulation will reduce the incidence of metabolic syndrome,
which, in turn, would
reduce the incidence of diabetes, CVD and obesity. This is the first herbal
combination with the
potential to have more significant effects than pharmaceutical drugs on this
triumvirate of
conditions which continues to have a major impact on the health of North
Americans.
Summary of the Invention
[0009] To this end, in one of its aspects, the present invention provides a
novel therapeutic
formulation which comprises cinnamon and bitter melon.
[0010] A further object of the present invention is to provide a new
therapeutic formulation
which comprises cinnamon and bitter melon in a ratio of seventy: thirty
(70:30).
Detailed Description of the Invention
[000111 The two active ingredients of the new therapeutic formulation are
cinnamon and
bitter melon. Both the plants are known to have hypoglycaemic properties in
traditional Chinese,
Indian and Caribbean Medicine.
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[00012] In recent years numerous laboratory and clinical studies have been
conducted on
these two plants by biological scientists, pharmacologists and pharmacists at
prestigious research
centres like Department of Pharmacy at the Kings College of London, University
of California,
Santa Barbara, Iowa State University and the U.S. Department of Agriculture.
All of these
studies show findings that confirm the therapeutic properties of the plants
claimed by the
traditional medicine and some of the research actually is considered to be
break through in the
field of natural health products. At USDA, scientists have been able to
identify the particular
molecule in cinnamon that mimics insulin and is responsible for its
hypoglycaemic properties.
[00013] The new therapeutic formulation contains cinnamon and bitter melon at
a ratio of
70:30 which is the most synergistic combination of the two plants for the
management of blood
sugar levels of type 2 diabetes patients as well as for normalizing the lipid
profiles.
[00014] The dietary habits of the developed countries such as Canada and
United States
have recently been criticized for causing an increase in the incidence of
several types of lifestyle-
related diseases such as diabetes, obesity and cardiovascular diseases.
Diabetes, a disorder of
carbohydrate, fat and protein metabolism attributed to diminished production
of insulin or
mounting resistance to its action, is the most common metabolic disease
presently. It is a major
cause of disability and hospitalization resulting in a significant financial
burden on the health
care system (Rathi et al. 2002 and Virdi et al. 2003), and is estimated to
cost Canadians up to $9
billion annually (Public Health Agency of Canada, 2005). It also has a
significant impact on the
health, quality of life and life expectancy of patients. Diabetes is a potent
risk factor for
cardiovascular disease as it not only affecting glucose metabolism but also
influences lipid
metabolism (Jayasooriya et al. 2000). Diabetes is divided into two major
categories: type 1
diabetes, previously known as insulin dependent diabetes mellitus (IDDM), and
type 2 diabetes,
previously known as non-insulin dependent diabetes mellitus (NIDDM). Although
the
recommended treatments for these two categories are usually somewhat
different, insulin for
IDDM and lifestyle management for NIDDM, the overall result is improving
glucose
homeostasis. Lifestyle management such as changes in diet and an exercise
regimen continues
to be essential and effective but it may be insufficient or difficult for
patient compliance
rendering conventional drug therapies useful (Dey et al. 2002). The problems
with the use of
insulin or any other antidiabetic drugs are the presence of adverse effects
such as hypoglycemia
at higher doses, liver problems, lactic acidosis and diarrhea (Virdi et al.
2003). In recent years,
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there has been a growing interest in herbal medicines specifically herbal
extracts as a popular
alternative in healthcare due to people's perception of it being a'natural'
product and therefore a
minimal chance of having any side effects. The current popularity is also due
to the many
botanicals reported for the management of diabetes in other alternative
systems of medicine such
as Ayurveda and Traditional Chinese Medicine, the interest in these herbal
plants has been
piqued.
[00015] The following is a brief description of the two ingredients and their
therapeutic
properties.
[00016] Cinnamomum aromaticum (sp. Cassia) is from the family Lauraceae. It is
a
medium-sized evergreen tree native to China and Vietnam. It contains volatile
oils composed of
cinnamaldehyde, phenolic compounds, flavonoid derivates, methylhydroxychalcone
polymer,
mucilage, calcium oxalate, resins, sugars, and coumarins. Cassia, the species
name for
Cinnamomum aromaticum comes from the Greek work "kassia" meaning "to strip off
the bark".
Cinnamon bark has been used medicinally in China since 2700 B.C.E and is said
to supplement
vital energy and blood, tone the kidney and spleen and acts as an antioxidant
(Blumenthal et al.
1998). Cinnamomum aromaticum has also been used in Korea, China and Russia as
a traditional
folk herb with hypoglycemic properties for the treatment of diabetes mellitus
(Kim et al. 2005).
The increasing prevalence of diabetes and cardiovascular disease is evident
worldwide with an
estimated 1700 new cases diagnosed daily (Jarvill-Taylor et al. 2001).
Additionally, several
million people worldwide are suffering from 'pre-diabetes' caused by high
glucose levels with a
resistance to insulin (Khan et al. 2003). The primary function of insulin is
to maintain low blood
glucose, lipid and cholesterol levels to maintain a sense of well-being.
Environmental factors
such as diet, exercise, and stress also attribute to decreasing insulin
sensitivity and increasing
glucose and low-density lipoprotein (LDL) cholesterol levels, increasing the
risk of
cardiovascular diseases, obesity, dyslipidemias, diabetes mellitus and
premature aging. The
increase in disease is partly due to the augmented intake of calories and
refined carbohydrates,
lesser consumption of fibers and a more sedentary lifestyle. Controlling
dietary intake and
exercise could prevent disease but the majority of individuals require an
extra aid to maintain
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normal health (Talpur et al., 2005). There is a growing interest in herbal
remedies due to the
side effects associated with therapeutic hypoglycemic agents and insulin (Kim
et al. 2005).
Botanical products with a long history of safety are widely used to lower
glucose, lipid and
cholesterol levels and for the prevention and treatment of diabetes.
[00017] Cinnamomum aromaticum has been used as a hypoglycemic agent in ancient
medicines (Kim et al. 2005). The modem therapeutic properties of cinnamon are
supportable
based on thousands of years of use in well established systems of traditional
medicines, as well
as some modem clinical studies (Blumenthal et al. 1998). A number of well
proven in vivo
animal studies on Cinnamomum aromaticum demonstrate that activation of the
insulin receptor
increases autophosphorylation resulting in an increase in glucose uptake and
glycogen synthesis.
However, there is a limited amount of published data on the effects of
cinnamon consumption on
blood glucose in humans. In vivo, in vitro and human studies have established
that cinnamon
extract regulates insulin activity and reduces serum glucose and cholesterol
levels (Khan et al.
2003 and Kim et al. 2005).
[00018] In a study by Khan et al. in 2003, 60 men and women with type 2
diabetes
ingested daily doses of cinnamon or placebo capsules for 40 days followed by a
20-day washout
period. Cinnamon capsules contained 1, 3 or 6 g of Cinnamomum aromaticum.
After 20 days,
only the 6 g cinnamon group showed significantly lower glucose levels.
However, after 40 days,
serum glucose (18-29%), triglycerides (23-30%) and total cholesterol (12-26%)
concentrations
were significantly lower in all cinnamon groups. Total cholesterol was lower
in all groups at 40
days but low-density lipoprotein (LDL) concentrations were only significantly
lower in the 3 g
and 6 g cinnamon groups (10% and 24%, respectively). For the 1 g cinnamon
group, LDL
concentrations continued to decline during the washout period and were
significant at 60 days
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(P<0.05). The decreased concentration of glucose was maintained by the 1 g
cinnamon group
while triglyceride and total cholesterol levels were maintained in all
cinnamon groups throughout
the 20-day washout period.
[00019] Vanschoonbeek et al. 2006 performed a 6 week standardized placebo-
controlled
study to investigate the proposed benefits of Cinnamomum cassia on 25
postmenopausal women
diagnosed with type 2 diabetes. Patients were divided into two groups and
supplemented with
1.5 g/day of Cinnamomum or placebo to assess the effects on glucose tolerance
and whole-body
insulin sensitivity. At 0, 2 and 6 weeks oral glucose tolerance tests and
blood lipid profiles were
performed resulting in no time x treatment interaction observed for fasting
glucose, insulin
concentration, insulin resistance, (oral glucose) insulin sensitivity or
fasting blood lipid
concentrations. This study shows cinnamon supplementation does not have a
health benefit in
patients with type 2 diabetes contradicting the results found by Khan et al.
2003. Differences
between the two studies could be attributed to the selection of patients and
the combination of
medications taken. In the current study, only postmenopausal female patients
were included and
continued using commonly prescribed combinations of oral blood glucose-
lowering agents,
which was not a factor in the study by Khan et al. 2003, explaining the low
baseline values found
in the patients used in the current study. Although the authors concluded
cinnamon
supplementation in combination with oral blood glucose-lowering agents may not
be beneficial
to overweight, postmenopausal women, this is a small concentrated study not
factoring in the use
of other medications and patient characteristics.
[00020] In a study by Talpur et al. in 2005, Zucker fatty rats (ZFRs) and
spontaneously
hyper-tensive rats (SHRs) were fed water or essential oils in acute or chronic
doses to assess the
effect of essential oil combinations on insulin sensitivity. The essential oil
treatment consisted of
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8 essential oils including cinnamon. Insulin sensitivity was determined by
systolic blood
pressure (SBP) and a glucose tolerance test. In the acute study, ZFRs and SHRs
with essential
oil treatments showed significant decreases in SBP at 4, 10 and 20 hours and
at 4 hours,
respectively. However, SBP levels were equal to the control group at 30 hours
in ZFRs and at
10, 20 and 30 hours in SHRs. In the chronic study, ZFRs and SHRs consuming the
essential oils
showed significantly lower SBP at 8, 17 and 25 days in comparison to the
control group.
Decreases in SBP levels ranged from 11 to 20 mmHg. During the oral glucose
test, ZFRs
consuming the essential oil combination showed consistently lower levels of
circulating insulin,
however these results were not significant. SHRs did not produce any effect on
insulin levels
and were equal to the controls, paralleling previous studies where effects
were only produced
when rats were challenged in stress-free environments (Verspohl et al. 2005).
The decreases in
SBP and circulating glucose levels, produced by both species of rats, enhance
insulin sensitivity
and parallels the idea that fluctuating SBP is the most sensitive index of
insulin sensitivity.
Cinnamon has been shown to have insulin-like actions and affect insulin
signaling (Broadhurst et
al. 2000), and as an ingredient in the essential oil combination it may have a
role in the reduction
of SBP.
[00021] In another study, Kim et al. 2006, administered db/db mice Cinnamomum
cassia
dosages of 50, 100, 150 or 200 mg/kg for 6 weeks to determine its effect on
blood glucose. The
control group showed high blood glucose levels at 2, 4, and 6 weeks. The
cinnamon extract-
treated group showed significantly lower blood glucose levels at each time
period (P<0.05, <0.01
and <0.001). Significant decreases in triglyceride and total cholesterol
levels were noted in the
cinnamon extract group. Similar to Khan et al. 2003 these results parallel the
hypoglycemic
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effects in the cinnamon extract-treated group as reduced levels are maintained
for a long period
of time.
[00022] In a similar study by Verspohl et al. in 2005, blood glucose and
plasma insulin
levels were evaluated in Wistar rats given extracts of Cinnamomum bark, cassia
or zeylanicum.
During the glucose tolerance test, plasma insulin levels increased
significantly after the
administration of Cinnamomum extracts with cassia showing the most pronounced
effect. The
saline placebo group showed no effect on plasma insulin. In all extract-
treated groups, blood
glucose levels did not decrease unless the rat was challenged by a glucose
tolerance test in a
stress-free environment. Cinnamomum cassia produced a direct insulin
stimulatory effect
showing superior effects compared to zeylanicum.
[00023] The increase in fructose consumption has risen worldwide in the past
two decades
as a significant proportion of energy intake in the diet. Qin et al. 2004 fed
18 male Wistar rats a
high-fructose diet and 6 a control diet for 3 weeks to determine the effects
of glucose utilization
and insulin sensitivity. 12 of the rats consuming a high-fructose diet had
Cinnamomum cassia
extracts (300 mg/kg/day) added to their diet. During the euglycemic clamp
procedure to
measure glucose infusion rates (GIR), the 6 rats consuming only a high-
fructose diet showed
significant decreases (p<0.0001) in glucose infusion rates while cinnamon
treated rats produced
significant increases, similar to the controls. The consumption of a high-
fructose diet, an
environmental factor contributing to diabetes, is common in the western
society; the addition of
Cinnamomum cassia extract to the diet shows a preventative effect, through an
increase in
glucose utilization and insulin sensitivity.
[00024] In another study, the effect of cinnamon extract on insulin action was
evaluated in
Wister rats. Qin et al. 2003 randomly assigned 18 rats into three groups:
saline, 30mg/kg and
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300mg/kg cinnamon extract. Cinnamon treatment for 3 weeks did not have an
effect on plasma
free fatty acids and fasting blood glucose concentrations. Although these
levels were not
affected in the cinnamon treated group, a difference was prevalent in glucose
uptake compared to
the placebo group. A dose-dependent manner was noticed with glucose
utilization as 300mg/kg
enhanced glucose utilization to a greater degree than the 30mg/kg or control
groups.
[00025] Methylhydroxychalcone polymer (MHCP), a bioactive compound of cinnamon
extract, is hypothesized to trigger an insulin-like response. In a study by
Jarvill-Taylor et al.
2001, 3T3-Ll adipocytes were assessed with MHCP to determine its function as
an insulin
mimetic. Within the first 10 minutes of incubation, the insulin treated
adipocytes showed a 2.5
fold increase in glucose transport while the MHCP treated group did not show
any increase.
However, gradually over the one-hour period, glucose uptake increased in the
MHCP treated
group and at 60 minutes, a significant increase was noted. As noted in other
studies, the effect of
cinnamon did not diminish immediately after stopping treatment. As MHCP is
administered, the
kinase receptor is activated resulting in phosphorylation of the insulin
receptor, a similar effect is
seen throughout the insulin signaling pathway.
[00026] A similar study by Broadhurst et al. in 2000 reported an increase in
insulin action
demonstrated by cinnamon extract in vitro. Rat epididymal adipocytes were
given either insulin
or cinnamon extract after incubation to determine glucose metabolism. At all
dilutions (1:2,
1:10, 1:50) cells exposed to cinnamon extract showed a significant increase in
insulin-dependent
activity and the effect was maintained at the high dilution (1:50). As
adipocytes were treated
with cinnamon extract the insulin receptor kinase became activated, a
necessary requirement to
increase insulin sensitivity. The activation of kinase mimics insulin activity
in adipocytes.
Afterwards, active cinnamon extract was incubated with soluble
polyvinylpyrrolidone (PVP) to
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CA 02551706 2006-06-27
determine if activity was associated with tannins or polyphenols. Cinnamon
readily bound to
PVP giving it a polyphenolic characterization. With an increase in glucose
metabolism, 98% of
activity is attributed to PVP indicating the use of phenolics to destroy free
radicals that inhibit
the activation of insulin-receptor kinase. Cinnamon extract mimics the same
mechanism as
insulin in adipocytes, increasing insulin sensitivity and glucose metabolism.
[00027] Cinnamomum aromaticum (cinnamon) has convincingly been shown to
prevent
and control elevated glucose and blood lipid concentrations in both in vitro
and in vivo studies
and can be maintained for a long period after use. The insulin kinase receptor
is activated with
cinnamon extract demonstrating insulin-mimetic activity. Elevated glucose and
blood lipid
concentrations increase the incidence of diabetes and/or cardiovascular
health. The use of
cinnamon extract can prevent these diseases by regulating the insulin receptor
to increase
glucose uptake and metabolism.
[00028] To date there have been no formal pharmacokinetic studies done on this
plant in
animals or humans. The only information derived from literature was a study
conducted by
Khan et al. in 2003 that found Cinnamomum aromaticum (extract) has a prolonged
effect on the
human body for 20 days during the washout period. Several animal studies have
also shown
prolonged effects after consumption of cinnamon extract.
[00029] The exact mechanism of action of Cinnamomum aromaticum (extract) is
thought
to be that it acts as an insulin-mimetic by activating the kinase receptor and
increasing insulin
sensitivity. The interaction within the intracellular kinase domain triggers
an insulin-like
response and stimulates glucose oxidation. Cinnamon also regulates enzymes
inside the insulin
receptor kinase domain and inhibits both phosphotyrosine-specific protein
phosphatase (PTP-1)
in vitro and glycogen synthase kinase-3(3 (GSK-3(3) in vivo. The inhibition of
PTP-1 keeps the
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CA 02551706 2006-06-27
insulin receptor in an activated state and inhibition of GSK-3(3 stimulates
glycogen production.
Cinnamon acts independently from insulin but similar levels of activity were
observed proposing
that it may activate the same cascade as the insulin signaling pathways
(Jarvill-Taylor et al.
2001).
[00030] Cinnamon significantly helps people with type 2 diabetes improve their
ability to
respond to insulin, thus normalizing their blood sugar levels. Both test tube
and animal studies
have shown that compounds in cinnamon not only stimulate insulin receptors,
but also inhibit an
enzyme that inactivates them, thus significantly increasing cells' ability to
use glucose. Studies
to confirm cinnamon's beneficial actions in humans are currently underway with
the most recent
report coming from researchers from the US Agricultural Research Service, who
have shown
that less than half a teaspoon per day of cinnamon reduces blood sugar levels
in persons with
type 2 diabetes. Their study included 60 Pakistani volunteers with type 2
diabetes who were not
taking insulin. Subjects were divided into six groups. For 40 days, groups 1,
2 and 3 were given
1, 3, or 6 grams per day of cinnamon while groups 4, 5 and 6 received placebo
capsules. Even
the lowest amount of cinnamon, 1 gram per day (approximately'/4 to V2
teaspoon), produced an
approximately 20% drop in blood sugar; cholesterol and triglycerides were
lowered as well.
When daily cinnamon was stopped, blood sugar levels began to increase.
[00031] Test tube, animal and human studies have all recently investigated
cinnamon's
ability to improve insulin activity, and thus our cells' ability to absorb and
use glucose from the
blood.
[00032] Ongoing in vitro or test tube research conducted by Richard Anderson
and his
colleagues at the USDA Human Nutrition Research Center is providing new
understanding of
the mechanisms through which cinnamon enhances insulin activity. In their
latest paper,
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published in the Journal ofAgricultural and Food Chemistry, Anderson et al.
characterize the
insulin-enhancing complexes in cinnamon-a collection of catechin/epicatechin
oligomers that
increase the body's insulin-dependent ability to use glucose roughly 20-fold..
Some scientists
had been concerned about potentially toxic effects of regularly consuming
cinnamon. This new
research shows that the potentially toxic compounds in cinnamon bark are found
primarily in the
lipid (fat) soluble fractions and are present only at very low levels in water
soluble cinnamon
extracts, which are the ones with the insulin-enhancing compounds.
[00033] A recent animal study demonstrating cinnamon's beneficial effects on
insulin
activity appeared in the December 2003 issue of Diabetes Research and Clinical
Practice. In this
study, when rats were given a daily dose of cinnamon (300 mg per kilogram of
body weight) for
a 3 week period, their skeletal muscle was able to absorb 17% more blood sugar
per minute
compared to that of control rats, which had not received cinnamon, an increase
researchers
attributed to cinnamon's enhancement of the muscle cells' insulin-signaling
pathway. In humans
with type 2 diabetes, consuming as little as 1 gram of cinnamon per day was
found to reduce
blood sugar, triglycerides, LDL (bad) cholesterol, and total cholesterol, in a
study published in
the December 2003 issue of Diabetes Care. The placebo-controlled study
evaluated 60 people
with type 2 diabetes (30 men and 30 women ranging in age from 44 to 58 years)
who were
divided into 6 groups. Groups 1, 2, and 3 were given 1, 3, or 6 grams of
cinnamon daily, while
groups 4, 5, and 6 received 1, 3 or 6 grams of placebo. After 40 days, all
three levels of
cinnamon reduced blood sugar levels by 18-29%, triglycerides 23-30%, LDL
cholesterol 7-27%,
and total cholesterol 12-26%, while no significant changes were seen in those
groups receiving
placebo. The researchers' conclusion: including cinnamon in the diet of people
with type 2
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CA 02551706 2006-06-27
diabetes will reduce risk factors associated with diabetes and cardiovascular
diseases.(January
28, 2004)
[00034] The latest research on cinnamon shows that by enhancing insulin
signaling,
cinnamon can prevent insulin resistance even in animals fed a high-fructose
diet! A study
published in the February 2004 issue of Hormone Metabolism Research showed
that when rats
fed a high-fructose diet were also given cinnamon extract, their ability to
respond to and utilize
glucose (blood sugar) was improved so much that it was the same as that of
rats on a normal
(control) diet. Cinnamon is so powerful an antioxidant that, when compared to
six other
antioxidant spices (anise, ginger, licorice, mint, nutmeg and vanilla) and the
chemical food
preservatives (BHA (butylated hydroxyanisole), BHT (butylated hydroxytoluene),
and propyl
gallate), cinnamon prevented oxidation more effectively than all the other
spices (except mint)
and the chemical antioxidants. (May 6, 2004).
[00035] In addition to its unique essential oils, cinnamon is an excellent
source of the trace
mineral manganese and a very good source of dietar.~~fiber, iron and calcium.
The combination
of calcium and fiber in cinnamon is important and can be helpful for the
prevention of several
different conditions. Both calcium and fiber can bind to bile salts and help
remove them from the
body. By removing bile, fiber helps to prevent the damage that certain bile
salts can cause to
colon cells, thereby reducing the risk of colon cancer. In addition, when bile
is removed by fiber,
the body must break down cholesterol in order to make new bile. This process
can help to lower
high cholesterol levels, which can be helpful in preventing atherosclerosis
and heart disease.
[00036] Cinnamaldehyde (also called cinnamic aldehyde) has been well-
researched for its
effects on blood platelets. Platelets are constituents of blood that are meant
to clump together
under emergency circumstances (like physical injury) as a way to stop
bleeding, but under
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CA 02551706 2006-06-27
normal circumstances, they can make blood flow inadequate if they clump
together too much.
The cinnaldehyde in cinnamon helps prevent unwanted clumping of blood
platelets. (The way it
accomplishes this health-protective act is by inhibiting the release of an
inflammatory fatty acid
called arachidonic acid from platelet membranes and reducing the formation of
an inflammatory
messaging molecule called thromboxane A2.) Cinnamon's ability to lower the
release of
arachidonic acid from cell membranes also puts it in the category of an "anti-
inflammatory" food
that can be helpful in lessening inflammation.
[00037] Cinnamon's essential oils also qualify it as an "anti-microbial" food,
and
cinnamon has been studied for its ability to help stop the growth of bacteria
as well as fungi,
including the commonly problematic yeast Candida. In laboratory tests, growth
of yeasts that
were resistant to the commonly used anti-fungal medicationfluconazole was
often (though not
always) stopped by cinnamon extracts.
[00038] Cinnamon's antimicrobial properties are so effective that recent
research
demonstrates this spice can be used as an alternative to traditional food
preservatives. In a study,
published in the August 2003 issue of the International Journal of Food
Microbiology, the
addition of just a few drops of cinnamon essential oil to 100 ml
(approximately 3 ounces) of
carrot broth, which was then refrigerated, inhibited the growth of the food
borne pathogenic
Bacillus cereus for at least 60 days. When the broth was refrigerated without
the addition of
cinnamon oil, the pathogenic B. cereus flourished despite the cold
temperature. In addition,
researchers noted that the addition of cinnamon not only acted as an effective
preservative but
improved the flavor of the broth.(October 1, 2003)
[00039] In addition to the active components in its essential oils and its
nutrient
composition, cinnamon has also been valued in energy-based medical systems,
such as
, .,. ,,. , ,, I~. ....._
. , . .. , , ..õ.....r....rr .r.A1x. ..xm........}rn.. . ...,... , . , .
CA 02551706 2006-06-27
Traditional Chinese Medicine, for its warming qualities. In these traditions,
cinnamon has been
used to provide relief when faced with the onset of a cold or flu, especially
when mixed in a tea
with some fresh ginger.
[00040] Bitter melon is of the family Cucurbitaceae, genus Momordica and
species
charantia. Some synonyms include Momordica chinensis, M. elegans, M. indica,
M. operculata,
M. sinensis, Sicyosfauriei, and its common names are bitter melon, papailla,
melao de sao
caetano, bittergourd, balsam apple, balsam pear, karela, k'u kua kurela, kor-
kuey, ku gua, pava-
aki, salsamino, sorci, sorossi, sorossie, sorossies, pare, peria laut, peria.
It may be used as a
whole plant, fruit or seed.
[00041] Bitter melon grows in tropical areas, including parts of the Amazon,
east Africa,
Asia, and the Caribbean, and is cultivated throughout South America as a food
and medicine. It's
a slender, climbing annual vine with long-stalked leaves and yellow, solitary
male and female
flowers borne in the leaf axils. The fruit looks like a warty gourd, usually
oblong and resembling
a small cucumber. The young fruit is emerald green, turning to orange-yellow
when ripe. At
maturity, the fruit splits into three irregular valves that curl backwards and
release numerous
reddish-brown or white seeds encased in scarlet arils. The Latin name
Momordica means "to
bite," referring to the jagged edges of the leaves, which appear as if they
have been bitten. All
parts of the plant, including the fruit, taste very bitter.
[00042] In the Amazon, local people and indigenous tribes grow bitter melon in
their
gardens for food and medicine. They add the fruit and/or leaves to beans and
soup for a bitter or
sour flavor; parboiling it first with a dash of salt may remove some of the
bitter taste.
Medicinally, the plant has a long history of use by the indigenous peoples of
the Amazon. A leaf
tea is used for diabetes, to expel intestinal gas, to promote menstruation,
and as an antiviral for
16
. ., õ ~a ,. i.. . , . CA 02551706 2006-06-27
measles, hepatitis, and feverish conditions. It is used topically for sores,
wounds, and infections
and internally and eacternally for worms and parasites.
[00043] In Brazilian herbal medicine, bitter melon is used for tumors, wounds,
rheumatism, malaria, vaginal discharge, inflammation, menstrual problems,
diabetes, colic,
fevers, worms. It is also used to induce abortions and as an aphrodisiac. It
is prepared into a
topical remedy for the skin to treat vaginitis, hemorrhoids, scabies, itchy
rashes, eczema, leprosy
and other skin problems. In Mexico, the entire plant is used for diabetes and
dysentery; the root
is a reputed aphrodisiac. In Peruvian herbal medicine, the leaf or aerial
parts of the plant are used
to treat measles, malaria, and all types of inflammation. In Nicaragua, the
leaf is commonly used
for stomach pain, diabetes, fevers, colds, coughs, headaches, malaria, skin
complaints, menstrual
disorders, aches and pains, hypertension, infections, and as an aid in
childbirth.
[00044] Bitter melon contains an array of biologically active plant chemicals
including
triterpenes, proteins, and steroids. One chemical has clinically demonstrated
the ability to inhibit
the enzyme guanylate cyclase that is thought to be linked to the cause of
psoriasis and also
necessary for the growth of leukemia and cancer cells. In addition, a protein
found in bitter
melon, momordin, has clinically demonstrated anticancerous activity against
Hodgkin's
lymphoma in animals. Other proteins in the plant, alpha- and beta-momorcharin
and cucurbitacin
B, have been tested for possible anticancerous effects. A chemical analog of
these bitter melon
proteins has been developed and named "MAP-30"; its developers reported that
it was able to
inhibit prostate tumor growth. Two of these proteins-alpha- and beta-
momorcharin-have also
been reported to inhibit HIV virus in test tube studies. In one study, HIV-
infected cells treated
with alpha- and beta-momorcharin showed a nearly complete loss of viral
antigen while healthy
cells were largely unaffected. MAP-30 has been claimed to be "useful for
treating tumors and
17
,_. , . ..,. . .,.,~. , ..,..
CA 02551706 2006-06-27
HIV infections... Another clinical study showed that MAP-30's antiviral
activity was also
relative to the herpes virus in vitro.
[00045] In numerous studies, at least three different groups of constituents
found in all
parts of bitter melon have clinically demonstrated hypoglycemic (blood sugar
lowering)
properties or other actions of potential benefit against diabetes mellitus.
These chemicals that
lower blood sugar include a mixture of steroidal saponins known as charantins,
insulin-like
peptides, and alkaloids. The hypoglycemic effect is more pronounced in the
fruit of bitter melon
where these chemicals are found in greater abundance.
[00046] Alkaloids, charantin, charine, cryptoxanthin, cucurbit,
cucurbitaceous,
cucurbitanes, cycloartenols, diosgenin, elaeostearic acids, erythrodiol,
galacturonic acids,
gentisic acid, goyaglycosides, goyasaponins, guanylate cyclase inhibitors,
gypsogenin,
hydroxytryptamines, karounidiols, lanosterol, lauric acid, linoleic acid,
linolenic acid,
momorcharasides, momorcharins, momordenol, momordicilin, momordicins,
momordicinin,
momordicosides, momordin, multiflorenol, myristic acid, nerolidol, oleanolic
acid, oleic acid,
oxalic acid, pentadecans, peptides, petroselinic acid, polypeptides, proteins,
ribosome-
inactivating proteins, rosmarinic acid, rubixanthin, spinasterol, steroidal
glycosides, stigmasta-
diols, stigmasterol, taraxerol, trehalose, trypsin inhibitors, uracil, vacine,
v-insulin, verbascoside,
vicine, zeatin, zeatin riboside, zeaxanthin, and zeinoxanthin are all found in
bitter melon.
[00047] To date, close to 100 in vivo studies have demonstrated the blood
sugar-lowering
effect of this bitter fruit. The fruit has also shown the ability to enhance
cells' uptake of glucose,
to promote insulin release, and to potentiate the effect of insulin. In other
in vivo studies, bitter
melon fruit and/or seed has been shown to reduce total cholesterol. In one
study, elevated
18
.,.. . ,~. ....
CA 02551706 2006-06-27
cholesterol and triglyceride levels in diabetic rats were returned to normal
after 10 weeks of
treatment.
[00048] Several in vivo studies have demonstrated the antitumorous activity of
the entire
plant of bitter melon. In one study, a water extract blocked the growth of rat
prostate carcinoma;
another study reported that a hot water extract of the entire plant inhibited
the development of
mammary tumors in mice. Numerous in vitro studies have also demonstrated the
anticancerous
and antileukemic activity of bitter melon against numerous cell lines,
including liver cancer,
human leukemia, melanoma, and solid sarcomas.
[00049] Bitter melon, like several of its isolated plant chemicals, also has
been
documented with in vitro antiviral activity against numerous viruses,
including Epstein-Barr,
herpes, and HIV viruses. In an in vivo study, a leaf extract increased
resistance to viral infections
and had an immunostimulant effect in humans and animals, increasing interferon
production and
natural killer cell activity.
[00050] In addition to these properties, leaf of bitter melon have
demonstrated broad-
spectrum antimicrobial activity. Various extracts of the leaves have
demonstrated in vitro
antibacterial activities against E. coli, Staphylococcus, Pseudomonas,
Salmonella,
Streptobacillus, and Streptococcus; an extract of the entire plant was shown
to have antiprotozoal
activity against Entamoeba histolytica. The fruit and fruit juice have
demonstrated the same type
of antibacterial properties and, in another study, a fruit extract
demonstrated activity against the
stomach ulcer-causing bacteria Helicobacter pylori.
[00051] Many in vivo clinical studies have demonstrated the relatively low
toxicity of all
parts of the bitter melon plant when ingested orally. However, toxicity and
even death in
laboratory animals has been reported when extracts are injected intravenously.
Other studies
19
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, . , . .,. .. .... . ,.,...,.,_ 44.,_.. ..,..~. K,l b..,,,.. ,.. . . . ..
CA 02551706 2006-06-27
have shown extracts of the fruit and leaf (ingested orally) to be safe during
pregnancy. The seeds,
however, have demonstrated the ability to induce abortions in rats and mice,
and the root has
been documented as a uterine stimulant in animals. The fruit and leaf of
bitter melon have
demonstrated an in vivo antifertility effect in female animals; and in male
animals, to affect the
production of sperm negatively.
[00052] Over the years scientists have verified many of the traditional uses
of this bitter
plant that continues to be an important natural remedy in herbal medicine
systems. Bitter melon
capsules and tinctures are becoming more widely available in the United States
and are
employed by natural health practitioners for diabetes, viruses, colds and flu,
cancer and tumors,
high cholesterol, and psoriasis. Concentrated fruit and seed extracts can be
found in capsules and
tablets, as well as whole herb/vine powders and extracts in capsules and
tinctures.
[00053] Bitter melon traditionally has been used as an abortive and has been
documented
with weak uterine stimulant activity; therefore, it is contraindicated during
pregnancy.
[00054] This plant has been documented to reduce fertility in both males and
females and
should therefore not be used by those undergoing fertility treatment or
seeking pregnancy.
[00055] The active chemicals in bitter melon can be transferred through breast
milk;
therefore, it is contraindicated in women who are breast feeding.
[00056] All parts of bitter melon (especially the fruit and seed) have
demonstrated in
numerous in vivo studies that they lower blood sugar levels. As such, it is
contraindicated in
persons with hypoglycemia.
[00057] Although all parts of the plant have demonstrated active antibacterial
activity,
none have shown activity against fungi or yeast. Long-term use of this plant
may result in the
die-off of friendly bacteria with resulting opportunistic overgrowth of yeast
(Candida). Cycling
_. ... .. , ,,.~, . .,. _
. .. ..... } ..,. , . . L... ln.,....a . .
CA 02551706 2006-06-27
off the use of the plant (every 21-30 days for one week) may be warranted, and
adding probiotics
to the diet may be beneficial if this plant is used for longer than 30 days.
[00058] Bitter melon may potentiate insulin and anti-diabetic drugs and
cholesterol-
lowering drugs.
1000591 As stated before, Momordica charantia or commonly referred to as
bitter melon
has been one of the most extensively investigated and most widely acclaimed
remedy for the
treatment of diabetes since ancient time as all parts of the plant (fruit
pulp, seed, leaves and
whole plant) have shown hypoglycemic activity in normal animals,
antihyperglycemic activity in
alloxan or streptozotocin-induced diabetic animals and in genetic models of
diabetes (Ahmed et
al. 2001, Virdi et al. 2003 and Grover and Yadav 2004). Bitter melon has been
observed to
decrease serum glucose levels in animal experiments and in a few
methodologically weak human
studies as these investigations were neither randomized nor blinded and the
dosage, toxicity and
adverse effects have not been systematically assessed (Basch et al. 2003).
Nonetheless, the
human, animal and in vitro evidence collectively suggests a moderate
hypoglycemic effect of
bitter melon.
[00060] A study by Akhtar et al. in 1981, investigated the effect of dried and
powdered M.
charantia fruit on blood glucose level following oral administration to normal
and alloxan-
diabetic rabbits. Both normal and diabetic rabbits were randomly divided into
5 groups of six
animals where group I served as a control whereas group II, III, IV and V were
treated orally
with 0.25, 0.5, 1.00 and 1.5 g/kg body weight of M. charantia powder suspended
in 1%
carboxymethyl cellulose solution in water respectively. Blood was collected
from an ear vein
immediately after M. charantia administration at 5, 10 and 24 hour time
intervals. There was no
decrease in blood glucose at a dose of 0.25 g/kg in normal rabbits and at 0.25
and 0.5 g/kg in
21
. . . . ... 4, õ ,w .. . .ilx....Fn.......1.
CA 02551706 2006-06-27
diabetic rabbits. The maximum glucose decrease was observed at 10 hours
intervals in both
normal and diabetic rabbits. A dose dependent decrease in blood glucose levels
was observed at
a dose of 1.0 and 1.5 g/kg in diabetic rabbits. The authors concluded that the
whole dried
powdered M. charantia fruit produced significant and consistent hypoglycemic
effect in both
normal and chemically induced insulin deficient rabbits.
[00061] In a study by Khanna et al. (1981), pharmacological trials on animals
and clinical
trials on humans were performed to investigate the effect of a hypoglycemic
agent, polypeptide-
p, isolated from the fruit, seeds and tissues of M. charantia. This active
principle was actually
isolated earlier by Khanna et al. in another study and was then called 'p-
insulin' or 'v-insulin'.
The pharmacological trials in gerbils and langurs revealed that the
polypeptide-p-ZnC12
administered subcutaneously was long acting and showed a significant blood-
sugar-lowering
effect. The clinical study also showed a hypoglycemic effect of polypeptide-p
in juvenile and
maturity-onset diabetic patients.
[00062] In a study by Leatherdale et al. (1981), the effect of M. charantia on
glucose and
insulin concentrations was studied in non-insulin dependent diabetics and non-
diabetic rats
during a 50 g oral glucose tolerance test. Patients underwent three 50 g oral
glucose tests: a
standard test, a test with 50 mL of juice extracted from fresh M. charantia
and a test after 8 - 11
weeks of consuming 0.23 kg of fried M. charantia daily. The rats were given 2
mL of the 10 mL
obtained from 100 g M. charantia. There was no associated increase in serum
insulin response
but blood glucose concentrations were significantly reduced in both patients
and rats with the
administration of raw juice whereas the daily supplement of fried M. charantia
produced a small
but significant improvement in glucose tolerance.
22
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CA 02551706 2006-06-27
[00063] In a similar study by Welihinda et al. (1986), the hypoglycemic
activity of M.
charantia was evaluated in non-insulin dependent maturity onset diabetics.
This study involved
18 patients with newly diagnosed type 2 diabetes mellitus. Each subject was
given 100 mL of
bitter melon juice 30 minutes before glucose loading for a glucose tolerance
test (GTT). The
results were compared to a GTT done on the previous day by each participant
that showed
significant improvements in GTT in 13 of the 18 participants (73%) after
taking bitter melon.
The other 5 patients showed no significant improvements in their glucose
tolerance. The authors
explained that this may have been due to intra-individual variation which is
normally seen in
biological systems.
[00064] A study by Day et al. (1990), investigated the hypoglycemic effect of
M.
charantia in normal mice by examining the plasma glucose and insulin responses
to oral and
intraperitoneal (i.p.) glucose tolerances and by examining different solvent-
extracted fractions of
M. charantia in streptozotocin diabetic mice. The hypoglycemic effect was
evident at 60
minutes after oral glucose and 60 and 120 minutes after i.p. glucose at a dose
of 1 g/mL. As in
the experiment with the diabetic mice, oral administration of aqueous extract
of M. charantia and
residue after alkaline chloroform extraction reduced plasma glucose
concentration within 1 hour
also at a dose of lg/mL. Material recovered by acid water wash of the
chloroform extract at a
dose of 0.002g/mL produced a slowly generated hypoglycemic effect. Orally
administered M.
charantia extracts lower glucose concentrations independently of intestinal
glucose absorption
and involves an extra-pancreatic action.
[00065] The hypoglycemic effects of fruit pulp, seed and whole plant of M.
charantia
were studied in normal, IDDM and NIDDM model rats by Ali et al. in 1993.
Diabetes
stimulating both IDDM and NIDDM were induced by i.p. injection of
streptozotocin. The
23
. . ,,., ~. ..~ . ..
CA 02551706 2006-06-27
results indicated that the hypoglycemic principle is present only in the fruit
pulp and that no
blood glucose lowering effect was seen in either normal or diabetic (IDDM and
NIDDM) rats
when given seed extracts. It was noted that the fruit pulp extracts showed
hypoglycemic activity
in normal and NIDDM rats whereas no effect was produced in the IDDM model
where P cells
have been almost completely destroyed. An indication that the hypoglycemic
effect of the active
principle is probably mediated either by improving the insulin-secretory
capacity of fl cells or by
improving the action of insulin
[00066] However, in a 2005 study by Sathishsekar and Subramanian, the
conclusion of the
study was that the administration of M. charantia seeds showed a hypoglycemic
effect. The
objective of the study was to examine the effect of aqueous extracts from
seeds of two varieties
of M. charantia on oxidative stress in plasma and the pancreas of
streptozotocin-induced diabetic
rats in comparison to a standard hypoglycemic drug, glibenclamide. Male albino
rats of Wistar
strain were divided into five groups of six animals in each group as follows:
normal control,
diabetic control, diabetic treated with seed extract 1, diabetic treated with
seed extract 2 and
diabetic administered with glibenclamide. The duration of the experiment was
30 days and then
the rats were sacrificed. The increase levels of blood glucose and decrease
level of insulin in
diabetic rats were normalized in M. charantia seed extract and glibenclamide
treated diabetic
rats. Also, the levels of thiobarbituric acid-reactive substances, lipid-
hydroperoxides and
reduced glutathione in both plasma and pancreas were significantly reversed to
near normalcy
after treatment. The levels of vitamin C and vitamin E in plasma and the
activities of superoxide
dismutase, catalase and glutathione peroxidase in pancreas were reversed to
near normal levels
and decreased activities respectively after M. charantia seed extract and
glibenclamide
treatment. Hence, controlling blood glucose level will thereby prevent the
formation of free
24
. . . . .. _.,A .,,.. . . . .. y, .I,.
ICA 02551706 2006-06-27
radicals or it may scavenge the reactive oxygen metabolites through various
antioxidant
compounds.
[00067] The antihyperglycemic effects of three extracts of fresh and dried
whole M.
charantia fruit were studied by Virdi et al. in 2003 and compared to
glibenclamide, a known
synthetic drug. After 4 weeks of treatment at a dose of 20 mg/kg body weight,
all three extract
powders lowered blood glucose however the aqueous extract showed the maximum
efficacy
comparable to that of glibenclamide. This extract was further tested for
nephrotoxicity,
hepatotoxicity and biochemical parameters. No toxicity to liver and kidneys
were shown based
on histological and biochemical parameters. In conclusion, the aqueous extract
powder of M.
charantia could be safely used in diabetic patients to control hyperglycemia
and taken on a long
term basis.
[00068] In 2001, Vikrant et al. carried out an experiment to study the effects
of different
doses of alcoholic and aqueous extracts of M. charantia on the metabolic
parameters of fructose
fed rats. Fructose feeding led to insulin resistance-hyperinsulinemia,
hyperglycemia and slight
elevation in serum triglycerides levels in which only aqueous extracts at the
dose of 400 mg/day
significantly prevented development of hyperglycemic as well as
hyperinsulinemia.
Consequently, M. charantia might prove useful in the treatment and/or
prevention of insulin
resistance in non-diabetic state.
[00069] In a study by Shetty et al. in 2005, male Wistar rats were rendered
diabetic by a
single injection of streptozotocin such that there were two groups of 12
diabetic rats and two
groups of 6 age-matched normal rats (control). Bitter gourd (M. charantia) was
incorporated at
10% level in the diet and glycemic control of bitter gourd during diabetes was
evaluated by
monitoring diet intake, gain in body weight, water intake, urine sugar, urine
volume, glomerular
. . . . r x. = rM..nMar. .r+.rl x...l...w....4 . .
CA 02551706 2006-06-27
filtration rate and fasting blood glucose profiles. The administration of
bitter gourd showed
significant reduction in urine excretion, urine sugar excretion, glomerular
filtration rate and
fasting blood glucose level. At the end of the experiment, there was
approximately 30%
improvement in the fasting blood glucose level and as such it is evident that
bitter gourd is
beneficial in controlling diabetes status.
[00070] In a study by Shibib et al. (1993), the biochemical mechanism of the
hypoglycemic activity of M. charantia was examined in streptozotocin-induced
diabetic rats.
The results of this study confirmed the hypoglycemic activity of M. charantia.
This activity was
mediated through the suppression of hepatic gluconeogenic enzymes, glucose-6-
phosphatase and
fructose-1, 6-bisphophatase while stimulating glucose-6-phosphatse
dehydrogenase. As such, M.
charantia is consistent with the antihyperglycemic effect reported in
literature.
[00071] Most of the experimental studies reported in literature on the
antihyperglycemic
activity of M. charantia were induced by alloxan or streptozotocin. However, a
study by Qakici
et al. in 1994 examined the hypoglycemic effect of orally administrated
extracts of M. charantia
in normoglycemic or cyproheptadine-induced hyperglycemic mice. Streptozotocin
or alloxan
are known to cause irreversible destruction of insulin-secreting fl-cells in
the islets of Langerhans
in comparison to cyproheptadine which produces a reversible loss of pancreatic
insulin when
given in repeated doses. When fed orally, the aqueous extract of M. charantia
but not the
ethanolic extract showed anti-hyperglycemic and hypoglycemic effects in
cyproheptadine-
induced hyperglycemic and normoglycemic mice respectively.
[00072] A study undertaken by Sarkar et al. in 1996, demonstrated the
hypoglycemic
activity of the alcoholic extract of M. charantia in a validated animal model
of diabetes mellitus
known to respond to oral hypoglycemic drugs. The reduction in plasma glucose
level was 10 -
26
õ . _. . ... , .. . .
. . . . . . n ...4 wr.M.. - .. i , do+n.r 1 ,... .
CA 02551706 2006-06-27
15% for M. charantia compared to a decrease of 40 - 44% for tolbutamide, a
sulphonylurea
drug, under similar conditions. Another finding was that repeated dosing of
500mg/kg of M.
charantia extract did not result in the deterioration of hypoglycemic response
in normal rats. In
diabetic rats, the oral glucose tolerance was improved causing a significant
reduction in plasma
glucose of 26% for M. charantia in comparison to metformin which caused a 40 -
50%
reduction. The hypoglycemic activity of M. charantia is confirmed in both
normal and diabetic
animals as reported in the literature with similar responses from oral
hypoglycemic drugs such as
tolbutamide and metformin.
[00073] I a similar study by Miura et al. (2001), the hypoglycemic activity of
the fruit of
M. charantia was investigated in an animal model with type 2 diabetes with
hyperinsulinemia.
After 3 weeks of oral administration of the water extract of M. charantia, the
blood glucose and
serum insulin levels were lowered. The results were supportive of the
traditional medical use of
M. charantia as an antidiabetic agent in type 2 diabetes.
[00074] In a follow up study, the effect of M. charantia with exercise on
blood glucose
was investigated as the treatment for type 2 diabetes (Miura et al. 2004).
Exercise therapy and
diet are usually recommended for type 2 diabetics and as such the inclusion of
exercise in this
study is investigated. After 5 weeks of oral administration of the water
extract of M. charantia
fruit with exercise, blood glucose and insulin levels in diabetic rats were
significantly reduced. It
was lower than that of M. charantia supplementation only or exercise only. The
hypoglycemic
effect of M. charantia with exercise is a synergistic effect that is
beneficial in type 2 diabetics.
[00075] The amount of research reported in literature on the beneficial
effects of M.
charantia are mostly concentrated on its antidiabetic activity despite the
possibility that it might
affect lipid metabolism due to the interconnection between carbohydrate and
lipid metabolism
27
. . . . . . .. . .. F.. ..6 . .. w x .Ml.n.. . . r.. II tl'x..r 1.I.=n . .
.4... , . . .
CA 02551706 2006-06-27
(Senanayake et al. 2004 (a)). People with diabetes mellitus are at a higher
risk of developing
heart disease and other blood vessel diseases as such there have been studies
reporting
hypertriglyceridaemia and hypercholesterolaemia in diabetic subjects
(Chaturvedi 2005). There
are a few experimental studies reported in literature that have examined the
effect of M.
charantia on triglyceride and cholesterol levels in normal and chemically
induced diabetic
animals.
[00076] In a study by Jayasooriya et al. in 2000, the effects of dietary
freeze-dried
powdered bitter melon on serum glucose level and lipid parameters of serum and
liver were
examined in rats fed with and without cholesterol. Male Sprague-Dawley rats
were fed the diets
for 14 days at 0.5, 1 and 3% without added dietary cholesterol and at a level
of 1% with or
without added cholesterol and 0.15% bile acid. Dietary bitter melon
consistently decreased
serum glucose levels in rats fed cholesterol-free diets. The addition of
bitter melon to
cholesterol-free and cholesterol-enriched diets caused an elevated serum HDL-
cholesterol level,
an indication of antiatherogenic activity. Also, there was a consistent
reduction of hepatic total
cholesterol and triglyceride levels both in the presence and absence of
dietary cholesterol where
the reduction of triglyceride concentrations, in absence of dietary
cholesterol, was in a dose-
dependent manner. These results suggest that bitter melon contains components
which influence
the metabolism of serum and liver lipids such that it may improve and/or
ameliorate lipid
disorders such as hyperlipidemia and fatty liver.
[00077] In 2001, Ahmed et al. performed a study to investigate the long term
effect of MC
fruit extract on blood plasma and tissue lipid profiles in normal and
streptozotocin (STZ)-
induced type 1 diabetic rats. Male Wistar rats were induced diabetic with a
single intraperitoneal
injection of a buffered solution of STZ at a dosage of 60 mg/kg body weight.
The animals were
28
. .,.....n Y ...,..aI.. r" +l ,..1rtu...4 ..
CA 02551706 2006-06-27
divided into four groups of six: diabetic, diabetic treated with karela
extract, karela treated
control and untreated control group. There was a significant increase in
plasma non-esterified
cholesterol, triglycerides and phospholipids in the diabetic rats accompanied
by a decrease in
HDL-cholesterol. However, over a 10-week treatment period with MC fruit
extract, these levels
returned close to normal. Also, under in vitro conditions, karela juice
exhibited an inhibitory
effect on membrane lipid peroxidation in a dose-dependant manner due to some
antioxidant
components present in the fruit extract. This study shows that besides its
known hypoglycemic
properties, karela fruit extract also exhibits strong hypolipidemic action on
diabetic
hypertriglyceridemia and hypercholesterolemia. Additionally, it has some
antioxidative
properties which contribute towards preventing lipid peroxidative damage.
[00078] In a study by Chen et al. (2003), the energy efficiency and adiposity
of male rats
were investigated with 0.375, 0.75 and 1.5% of bitter melon supplementations
in high fat and
low fat diets. Rats on the high fat diet with 1.5% bitter melon gained less
weight and had less
visceral fat than those fed the high fat diet. Bitter melon supplementation
did not change
apparent fat absorption but improved insulin resistance, lowered serum insulin
and leptin but
raised serum free fatty acid concentrations. The reduction of adiposity in
rats fed a high fat diet
indicates bitter melon has influences on lipid metabolism other than glucose
metabolism.
[00079] Chen et al. carried out another study in 2005 to further investigate
the metabolic
consequences and possible mechanism(s) of the above study results. Bitter
melon
supplementation of 0.75 or 1.5% in either low-fat or high-fat diet had lower
energy efficiency,
visceral fat mass, plasma glucose and hepatic triacylglycerol but higher serum
free fatty acids
and plasma catecholamines indicating an enhanced sympathetic activity and
lipolytic process.
29
õ , , . :.,. õ .. , . . i
CA 02551706 2006-06-27
This clearly demonstrated the ability of bitter melon supplementation to
reverse steatosis and
normalize hepatic triacylgleycerol.
1000801 In a study by Senanayake et al. (2004 (b)), the effects of three
different varieties
of bitter melon on serum and liver lipids were examined. The effects on serum
lipid parameters
were marginal for all three varieties. On the other hand, all three varieties
of bitter melon
lowered hepatic triglyceride levels but the Koimidori variety was found to be
the most effective.
Further investigation on this variety was carried out on finding the active
component(s) of bitter
melon responsible for liver triglyceride lowering activity by fractionation
the bitter melon using
organic solvents such as n-hexane, acetone, and methanol. The liver
triglyceride levels in rats
fed diets containing the methanol fraction at 1% level was similar to those
fed unfractionated
Koimidori at 3%. Therefore, the potent active component of bitter melon
lowering liver
triglyceride concentrations is found to be concentrated in the methanol
fraction. The methanol
fraction was able to lower liver cholesterol concentration in a dose-dependent
manner. Hence,
bitter melon is useful in relieving and/or ameliorating life style-related
diseases such as fatty
liver, hypertriglyceridemia and diabetes.
[000811 The authors from the above study carried out a very similar experiment
using only
the bitter melon of the Koimidori variety at levels of 0.5 and 1% to examine
its hypolipidemic
effect in Syrian hamsters fed a diet supplemented with and without 0.2%
cholesterol
(Senanayake et al. 2004(a)). The serum triglyceride-lowering activity of
dietary methanol
fraction extracted from bitter melon was observed in a dose-dependent manner
in hamsters fed
diets with no added cholesterol. This dose-dependent triglyceride lowering
effect was also seen
in hamsters fed cholesterol-enriched diet supplemented with bitter melon. Even
though elevated
liver triglyceride levels were caused by the dietary cholesterol, these levels
were still lower with
. . . ... ..:.......... 4 .wm.xYx..... x N.x.. 4+,..y. ....p.. .,. ..
CA 02551706 2006-06-27
bitter melon supplements. As a result, dietary bitter melon extract is
effective in lowering serum
and liver triglyceride especially in those with hypertriglyceridemia caused by
dietary cholesterol.
[00082] In a more detailed study by Chaturvedi et al. (2004), the methanol
extract of the
fruit M. charantia was administered to diabetic rats to assess the long term
effect of the extract
on lipid profile and oral glucose tolerance test. After 30 days treatment,
there was a significant
reduction in triglyceride and LDL, and a significant increase in HDL level. A
significant effect
on oral glucose tolerance was also noted but more obvious when the extract was
given on the
same day as the test.
[00083] In 2005, Chaturvedi performed a study to assess whether or not a
methanol extract
of M. charantia was able to normalize lipid and glucose levels in diabetic
rats fed a high-fat and
low-carbohydrate diet. Different doses of the extract were administered to
alloxan-induced
diabetic albino rats of the Horts Men strain for 45 days. Blood glucose,
triglyceride, LDL and
HDL levels showed a dose-dependent response to M. charantia extract while
cholesterol levels
were found to be significantly lower. M. charantia extract normalized blood
glucose level,
reduced triglyceride and LDL levels and increased HDL level. Hence, M.
charantia can play an
active part in the management of diabetes and have a positive impact on
factors responsible for
heart diseases and other related disorders.
[00084] To date there have been no formal pharmacokinetic studies done on this
plant in
animals or humans. This may be due to the fact that they are commonly consumed
as a
vegetable. Hence, the absorption of bitter melon occurs in the intestinal
tract. It is absorbed into
the blood to affect glucose metabolism and incorporated into hepatic tissues
to influence the
metabolism of triglyceride (Jayasooriya et al. 2000 and Senanayake et al. 2004
(b)). The
31
õ._, .... _ ,
. _ i . w. . k . ..,. ., 4 .
CA 02551706 2006-06-27
pharmacologic effects of the insulin-like polypeptide contained in bitter
melon have an onset
ction between 30 and 60 minutes and a peak effect at about four hours (Jellin
et al. 2005).
[00085] The exact mechanism of action of Momordica charantia in animals and
humans
has not been elucidated; however investigators have proposed many plausible
theories based on
experimental results.
[00086] This effect seems to be through a number of different mechanisms. One
of the
earlier theory was that a component of bitter melon extract, polypeptide-p,
have structural
similarities to bovine insulin and as such the hypoglycemic activity (Khanna
et al. 1981 and
Basch et al. 2003). Other hypoglycemic chemicals of Momordica charantia
include a mixture of
steroidal saponins known as charantin, momordin Ic, oleanolic acid 3-0-
monodesmoside and
oleanolic acid 3-0-glucuronide (Grover and Yadav 2004). The mechanisms
proposed for effects
on glucose and insulin include an inhibitory effect on glucose absorption in
the intestine by
decreasing hepatic gluconeogenesis, increasing hepatic glycogen synthesis and
increasing
peripheral glucose oxidation (Shibib et al. 1993 and Basch et al. 2003),
enhanced insulin release
from beta cells (Sitasawad et al. 2000 and Saxena and Vikram 2004) and an
extrapancreatic
effect via increased glucose uptake by tissues and increased GLUT4 transporter
protein of
muscles (Day et al. 1990, Sarkar et al. 1996 and Miura et al. 2001).
[00087] The hypolipidemic effect of Momortica charantia has not been as
extensively
studied as the hypoglycemic effect; however, the mechanism of action that has
been proposed by
investigators based on experimental studies include controlling the hydrolysis
of certain
lipoproteins through enhanced sympathetic activity, lipolysis and possibly
lipid oxidation, for
selective uptake and metabolism by different tissues (Ahmed et al. 2001, Chen
et al. 2003 and
Chen and Li 2005), and bitter melon contains some active components, saponin
and plant sterols
32
, .. . :. y..., =.xx..., . ,.a1. ....a,.. ..,... ... .. . CA 02551706 2006-06-
27
that are known to have an inhibitory effect on lipid biosynthesis thus
lowering liver triglyceride
levels in animals and inhibiting cholesterol absorption in the intestinal
tract (Senanayake et al.
2004 (a & b)). The strong antihyperlipidemic effect of M. charantia could also
be explained
through its control of hyperglycemia as insulin is a major determinant of
total and very low
density lipoprotein and triglyceride concentration (Ahmed et al. 2001). The
hyperlipidemia
observed in diabetics is a consequence of uninhibited action of lipolytic
hormones on fat depots
as insulin inhibits adipose tissue hormone-sensitive lipase reducing lipolysis
and mobilization of
peripheral depots (Ahmed et al. 2001).
[00088] Much literature has been published on bitter melon and cinnamon. A
partial
listing of the published research on bitter melon is provided in Schedule A
and a partial listing of
the published research on cinnamon is provided in Schedule B.
[00089] The present inventors have shown that the new therapeutic formulation
comprising cinnamon and bitter melon demonstrates synergist activity and inter
alia:
(a) healthy glucose level for people with type 2 diabetes;
(b) optimum level of cholesterol and triglycertides for people of all ages and
thus
reduces the risk of cardiovascular disease.
[00090] Thee new therapeutic formulation has also been proven as a powerful
antioxidant
and effective in helping to prevent cancer, heart disease, and stroke.
[00091] Another major benefit of the new therapeutic formulation is that it
can prevent
insulin resistance, a major and common complication that develops in people
with type II
diabetes in later years.
[00092] The two main ingredients of the new therapeutic formulation come from
cinnamon and bitter melon, two natural products with long history both as
foods and as
medicines. Both the ingredients have been successfully used as effective
remedies for many
medical conditions in Indian, Chinese and South American Traditional Medicine.
33
.. ,, ..,...,.,. .., . ..... ,
. , . . . . ........F .w u Nn ... ,, ..n.,N..s n..Nw w=.,. .p...,.
CA 02551706 2006-06-27
[00093] The mechanism of actions are different from one another as cinnamon
activates
the insulin kinase receptor to increase insulin sensitivity through insulin-
mimetic activity while
the mechanisms for bitter melon include increased insulin secretion, tissue
glucose uptake, liver
muscle glycogen synthesis, glucose oxidation and decreased hepatic
gluconeogenesis. As a
result, combining these two ingredients has a synergistic effect which would
lead to greater
benefits for people with diabetes. Also, it has been observed that people with
diabetes are
usually associated with hypertriglyceridemia and hypercholesterolemia.
Therefore, the
combination of cinnamon and bitter melon has the potential to treat and
prevent diabetes and
other related cardiovascular diseases by lowering blood glucose levels and
normalizing lipid
profiles. Therefore, the combination of the medicinal ingredients is both
novel and innovative.
[00094] The ratio of cinnamon to bitter melon may be varied and it is
preferred that it be
between sixty to seventy percent (60 - 70%) of cinnamon and forty to thirty
percent (40 - 30%)
of bitter melon.
[00095] One new therapeutic formulation contains cinnamon and bitter melon at
a ratio of
60:40 which is the most synergistic combination of the two plants for the
management of blood
sugar levels of type 2 diabetes patients as well as for normalizing the lipid
profiles. The new
therapeutic formulation also contains the highest concentration of water
soluble flavonoids
extracted from cinnamon ( the part of the cinnamon extract responsible for its
blood sugar
lowering effect) compared to any other similar products in the market.
[00096] In order to achieve the desired synergism, the dosage of bitter melon
should in the
range of 100 to 200 milligrams two to three times a day with at least one gram
of cinnamon per
day. A particularly useful preparation is a 500 milligram capsule containing
about 200
milligrams of bitter melon and 300 milligrams of cinnamon and one capsule
should be taken
twice a day to achieve the desired dosage.
[00097] Examples:
One particularly useful formulation is as follows:
Cinnamon (Cinnamomi cassiae: Cinnamonum verum) 280 mg
Bitter melon (Momordica charantia) 120 mg
Diluent 151 mg
Lubricant 3 mg
34
,. , .... ,,,, . õ .. . ,.. .. ,
. . . .............. , r.,..,L., ... w..w.,. . , ..l.e x. .1a. ,..,.p_.... ,.
CA 02551706 2006-06-27
[00098] The bark of cinnamon was used in a ratio of 10:1 to produce the active
ingredient.
Similarly, the whole melon was used in a ration of 10:1 to produce the desired
amount of bitter
melon. As the diluent, it was found useful to use microcrystalline cellulose
in the amount of 150
milligrams mixed with one (1) milligram of dicalcium phosphate dihydrate.
Magnesium stearate
was used as the lubricant. The ingredients were mixed and placed in a gelatin
capsule.
Administration was also found to lower blood sugar levels and to normalize
lipid profiles.
[00099] The inventors have also found that a timed release formulation is
useful to reduce
blood glucose levels. Tests have shown that blood glucose levels of a person
in the morning are
at a fasting level, that is, about 4 to 5 mmol/L. This is as a result of the
body using up all the
carbohydrates which were injested at supper the previous evening plus any
snacks. After
breakfast, the blood glucose levels rise steadily within one-half hour,
peaking at about one hour
then beginning to fall back towards the fasting level or just above it over
the next two or three
hours. This pattern is cyclical after each meal. At night, the level drops and
if below the fasting
level, the hormone glucagon is produced by the body to break down the glycogen
into its glucose
units and releases them to the bloodstream. If the glycogen is depleted for
any reason,
gluconeogenesis takes place to produce new glucose.
[000100] In other words, the blood glucose levels are under very tight control
in the body.
If they are too high, insulin is produced which drives excess blood glucose
into the cells. If the
levels are too low, glycogen is produced to raise the blood glucose levels. In
Type 2 diabetes,
there is little or no insulin available or its receptors are missing from the
cells or it is
substandard. Whatever the case, it is not available to push the excess glucose
into the cells so
that the blood glucose levels rise and diabetics must get exogenous insulin to
stop this from
happening.
[000101] Therefore, a timed release preparation may be preferred and assists
in returning
blood glucose levels over a significant period of time.
[000102] In order to achieve the appropriate timed release of the
cinnamon/bitter melon, it
is preferred to prepare a compressed tablet (CT) which will release the
cinammon/bitter melon
over the desired period of time. For example, if a CT containing 200 mg of
bitter melon and 300
mg of cinnamon were ingested in the morning, the release of the medication
would take place
over a twelve hour period. A further CT taken in the evening would release the
medication
throughout the night thereby providing a level amount of blood glucose levels.
,. _õ .... ,,,. , . .,.. .. ,
..,..p... n4 w IHIx.. .n Il..x....w+ . 4.. .
CA 02551706 2006-06-27
[000103] In order to achieve an appropriate timed release preparation, the
inventors have
found that a tablet comprising 500 mg of the cinnamon/bitter melon
combination, from about
0.5% to about 3% of a lubricant, glidant and antiadherent; about 30% to about
50% of a
compression agent and from about 0.5% to about 25% of a modified release agent
will achieve
the desired result.
[000104] Suitable lubricants, glidants and antiadherents include calcium,
stearate,
magnesium stearate, zinc stearate, stearic acid, talc, collidal silicas,
sodium, benzoate
polyethylene glycol, microscopic fumed silicas, micro-sized silicas.
[000105] Suitable compression agents may be selected from lactose, dicalcium
phosphate
anhydrous, dicalcium phosphate dihydrate, mannitol, sorbitol, microcrystalline
cellulose, starch,
corn-syrup solids, dextrose monohydrous, dextrose anhydrous, dextrose corn
syrup, sucrose,
fructose.
[000106] Appropriate modified release agents may include corn starch, modified
starches,
cellulose, alginic acid, sodium alginate, amonium calcium alginate,
hydroxypropyl
methylcellulose, sodium starch glycolate, sodium carboxymethylcellulose,
colloidal silicates, ion
exchange resin, wax, polyvinylpolyprrolidone, polyvinylpropalene.
[000107] The table is prepared using conventional compression techniques.
[000108] Although the disclosure describes a preferred embodiment, the
invention is not so
limited. For a definition of the invention, reference is made to the claims.
36
_ _. _. ., ...:x,,. .,,. ........_,
. . .. _ . .. .. .....,n --- .. , .+..,... .~.. .
CA 02551706 2006-06-27
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.. _._ ,_ ..,,.,,,,. . õ .. .... .__ .,
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_..:w_wõ....,..,,... ,.,.,...,..... ,
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.. . ..,. ,,. õ .. . . _ .._ ,
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Prakash, A. 0., et al. "Screening of Indian plants for antifertility
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Stepka, W., et al. "Antifertility investigation on Momordica." Lloydia. 1974;
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U.S. Patents:
PAT. NO. Title
1 7,014,872 Herbal nutraceutical formulation for diabetics and process for
preparing
the same
2 6,964,786 Oil from Momordica charantia L., its method of preparation and
uses
3 6,960,348 Goya derived cosmetic compositions for face and body
4 6,831,162 Protein/polypeptide-k obtained from Momordica charantia and a
process
for the extraction thereof
6,800,726 Proteins with increased levels of essential amino acids
6 6,770,585 Momordica cochinchinensis (Spreng.) .beta.-carotene and method
7 6,562,379 Adult-onset diabetes treatment method
8 6,379,718 Use of plant extracts for treatment of acne and furuncle
9 6,235,286 Adult-onset diabetes treatment method
6,183,747 Use of plant Momordica charactia extracts for treatment of acne acid
11 6,103,240 Herbal sweetening and preservative composition comprising
licorice
extract and mogrosides obtained from plants belonging to cucurbitaceae
and/or momordica
12 5,942,233 Herbal composition for stimulating blood circulation
13 5,929,047 Anti-viral agent prepared by basic and acidic extraction of
mangraves
14 5,900,240 Herbal compositions and their use as hypoglycemic agents
5,851,531 Adult-onset diabetes treatment method
16 5,484,889 Plant protein useful for treating tumors and HIV infection
17 4,368,149 Protein hybrid having c otoxicity and process for the preparation
thereof
18 4,084,010 Glycosides having sweetness
42
i .,. ,.. ,
CA 02551706 2006-06-27
1: Khan B, Arayne MS, Naz S, Mukhtar N.
Hypogylcemic activity of aqueous extract of some indigenous plants.
Pak J Pharm Sci. 2005 Jan;18(1):62-4.
PMID: 16431387 [PubMed - indexed for MEDLINE]
2: Reyes BA, Bautista ND, Tanquilut NC, Anunciado RV, Leung AB, Sanchez GC, Ma
tg oto
RL, Castronuevo P, Tsukamura H, Maeda KI.
Anti-diabetic potentials of Momordica charantia and Andrographis paniculata
and their
effects on estrous cyclicity of alloxan-induced diabetic rats.
J Ethnopharmacol. 2005 Nov 16; [Epub ahead of print]
PMID: 16298503 [PubMed - as supplied by publisher]
3: Ansari NM, Houlihan L, Hussain B, Pieroni A.
Antioxidant activity of five vegetables traditionally consumed by South-Asian
migrants in
Bradford, Yorkshire, UK.
Phytother Res. 2005 Oct;19(10):907-11.
PMID: 16261524 [PubMed - indexed for MEDLINE]
4: Yang X, Kong C, Liang W, Zhang M, Hu F.
[Relationships of Aulacophora beetles feeding behavior with cucurbitacin types
in host crops]
Ying Yong Sheng Tai Xue Bao. 2005 Jul;16(7):1326-9. Chinese.
PMID: 16252877 [PubMed - in process]
5: Dengiz GO, Gursan N.
Effects of Momordica charantia L. (Cucurbitaceae) on indomethacin-induced
ulcer
model in rats.
Turk J Gastroenterol. 2005 Jun;16(2):85-88.
PMID: 16252198 [PubMed - as supplied by publisher]
6: Chan LL, Chen O, Go AG, Lam EK, Li ET.
Reduced adiposity in bitter melon (Momordica charantia)-fed rats is associated
with increased
lipid oxidative enzyme activities and uncoupling protein expression.
J Nutr. 2005 Nov;135(11):2517-23.
PMID: 16251604 [PubMed - indexed for MEDLINE]
7: Shekelle PG, Hardy M, Morton SC, Coulter I, Venuturupalli S, Favreau J,
Hilton LK.
Are Ayurvedic herbs for diabetes effective?
J Fam Pract. 2005 Oct;54(10):876-86. Review.
PMID: 16202376 [PubMed - indexed for MEDLINE]
8: Chaturvedi P.
Role of Momordica charantia in maintaining the normal levels of lipids and
glucose in
diabetic rats fed a high-fat and low-carbohydrate diet.
Br J Biomed Sci. 2005;62(3):124-6.
PMID: 16196458 [PubMed - indexed for MEDLINE]
43
. . . . h...l. ...... . .. . i. ,.. I .
CA 02551706 2006-06-27
9: Mekuria DB, Kashiwagi T, Tebayashi S, Kim CS.
Cucurbitane triterpenoid oviposition deterrent from Momordica charantia to the
leafininer,
Liriomyza trifolii.
Biosci Biotechnol Biochem. 2005 Sep;69(9):1706-10.
PMID: 16195588 [PubMed - indexed for MEDLINE]
10: Girini MM, Ahamed RN, Aladakatti RH.
Effect of graded doses of Momordica charantia seed extract on rat sperm:
scanning electron
microscope study.
J Basic Clin Physiol Pharmacol. 2005;16(1):53-66.
PMID: 16187486 [PubMed - indexed for MEDLINE]
11: Shetty AK, Kumar GS, Sambaiah K, Salimath PV.
Effect of bitter gourd (Momordica charantia) on glycaemic status in
streptozotocin induced
diabetic rats.
Plant Foods Hum Nutr. 2005 Sep;60(3):109-12.
PMID: 16187012 [PubMed - indexed for MEDLINE]
12: Hsieh CL, Lin YC, Ko WS, Peng CH, Huang CN, Peng RY.
Inhibitory effect of some selected nutraceutic herbs on LDL glycation induced
by glucose
and glyoxal.
J Ethnopharmacol. 2005 Dec 1;102(3):357-63. Epub 2005 Sep 12.
PMID: 16162395 [PubMed - indexed for MEDLINE]
13: Long-Yun L, Shu S, Wei YF, Zhong GY, Chen JH.
[Morphological and histological studies of Herpetospermum pedunculosum seeds
and other
substitutes]
Zhongguo Zhong Yao Za Zhi. 2005 Jul;30(14):1073-6. Chinese.
PMID: 16161440 [PubMed - in process]
14: Li LY, Deji LM, Wei YF, Zhong GY.
[Literature data investigation in semem of Herpetospermum pedunculosum]
Zhongguo Zhong Yao Za Zhi. 2005 Jun;30(12):893-5. Chinese.
PMID: 16124602 [PubMed - in process]
15: Zheng ZX, Teng JY, Liu JY, Qiu JH, Ouyang H, Xue C.
[The hypoglycemic effects of crude polysaccharides extract from Momordica
charantia in
mice]
Wei Sheng Yan Jiu. 2005 May;34(3):361-3. Chinese.
PMID: 16111053 [PubMed - in process]
16: Mutalik S Chetana M, Sulochana B, Devi PU, Udupa N.
Effect of Dianex, a herbal formulation on experimentally induced diabetes
mellitus.
Phytother Res. 2005 May;19(5):409-15.
PMID: 16106394 [PubMed - indexed for MEDLINE]
44
. . . , .~, .. .~ - ..
CA 02551706 2006-06-27
17: Akhtar S, Ali Khan A, Husain Q.
Partially purified bitter gourd (Momordica charantia) peroxidase catalyzed
decolorization of
textile and other industrially important dyes.
Bioresour Technol. 2005 Nov;96(16):1804-11. Epub 2005 Feb 25.
PMID: 16051087 [PubMed - indexed for MEDLINE]
18: Raj SK, Khan MS, Singh R, Kumari N, Prakash D.
Occurrence of yellow mosaic geminiviral disease on bitter gourd (Momordica
charantia) and
its impact on phytochemical contents.
Int J Food Sci Nutr. 2005 May;56(3):185-92.
PMID: 16009633 [PubMed - indexed for MEDLINE]
19: Kumar Shetty A, Suresh Kumar G, Veerayya Salimath P.
Bitter gourd (Momordica charantia) modulates activities of intestinal and
renal
disaccharidases in streptozotocin-induced diabetic rats.
Mol Nutr Food Res. 2005 Aug;49(8):791-6.
PMID: 16007724 [PubMed - indexed for MEDLINE]
20: Liu HL, Kong LY, Takaya Y, Niwa M.
Biotransformation of ferulic acid into two new dihydrotrimers by Momordica
charantia
peroxidase.
Chem Pharm Bull (Tokyo). 2005 Jul;53(7):816-9.
PMID: 15997142 [PubMed - indexed for MEDLINE
21: Chen , Li ET.
Reduced adiposity in bitter melon (Momordica charantia) fed rats is associated
with lower
tissue triglyceride and higher plasma catecholamines.
Br J Nutr. 2005 May;93(5):747-54.
PMID: 15975176 [PubMed - indexed for MEDLINE]
22: Yasui Y, Hosokawa M, Sahara T, Suzuki R, Ohgiya S, Kohno H, Tanaka T,
Miyashita K.
Bitter gourd seed fatty acid rich in 9c,11t,13t-conjugated linolenic acid
induces apoptosis
and up-regulates the GADD45, p53 and PPARgamma in human colon cancer Caco-2
cells.
Prostaglandins Leukot Essent Fatty Acids. 2005 Aug;73(2):113-9.
PMID: 15961301 [PubMed - indexed for MEDLINE]
23 : Ike K, Uchida Y, Nakamura T, Imai S.
Induction of interferon-gamma (IFN-gamma) and T helper 1(Thl) immune response
by
bitter gourd extract.
J Vet Med Sci. 2005 May;67(5):521-4.
PMID: 15942138 [PubMed - indexed for MEDLINE]
e4 =n r , n 14-n r- .{ r nr4... .
CA 02551706 2006-06-27
24: Sathishsekar D, Subramanian S.
Beneficial effects of Momordica charantia seeds in the treatment of STZ-
induced diabetes in
experimental rats.
Biol Pharm Bull. 2005 Jun;28(6):978-83.
PMID: 15930730 [PubMed - indexed for MEDLINE]
25: Sathishsekar D, Subramanian S.
Antioxidant properties of Momordica Charantia (bitter gourd) seeds on
Streptozotocin
induced diabetic rats.
Asia Pac J Clin Nutr. 2005;14(2):153-8.
PMID: 15927932 [PubMed - indexed for MEDLINE]
26: Akhtar S, Khan AA, Husain Q.
Potential of immobilized bitter gourd (Momordica charantia) peroxidases in the
decolorization and removal of textile dyes from polluted wastewater and dyeing
effluent.
Chemosphere. 2005 Jul;60(3):291-301. Epub 2005 Jan 26.
PMID: 15924947 [PubMed - indexed for MEDLINE]
27: Kimura Y, Akihisa T, Yuasa N, Ukiya M, Suzuki T, Toriyama M, Motohashi S,
Tokuda H.
Cucurbitane-type triterpenoids from the fruit of Momordica charantia.
J Nat Prod. 2005 May;68(5):807-9.
PMID: 15921438 [PubMed - indexed for MEDLINE]
28: Sekar DS, Sivagnanam K, Subramanian S.
Antidiabetic activity of Momordica charantia seeds on streptozotocin induced
diabetic rats.
Pharmazie. 2005 May;60(5):383-7.
PMID: 15918591 [PubMed - indexed for MEDLINE]
29: Sultan NA, Swamy MJ.
Energetics of carbohydrate binding to Momordica charantia (bitter gourd)
lectin: an
isothermal titration calorimetric study.
Arch Biochem Biophys. 2005 May 1;437(1):115-25.
PMID: 15820223 [PubMed - indexed for MEDLINE]
30: Nerurkar PV, Pearson L, Efird JT, Adeli K, Theriault AG, Nerurkar VR.
Microsomal triglyceride transfer protein gene expression and ApoB secretion
are inhibited
by bitter melon in HepG2 cells.
J Nutr. 2005 Apr;135(4):702-6.
PMID: 15795421 [PubMed - indexed for MEDLINE]
31: Yadav UC, Moorthy K, BMuer NZ.
Combined treatment of sodium orthovanadate and Momordica charantia fruit
extract
prevents alterations in lipid profile and lipogenic enzymes in alloxan
diabetic rats.
Mol Cell Biochem. 2005 Jan;268(1-2):111-20.
PMID: 15724444 [PubMed - indexed for MEDLINE]
46
. . . ...4 ,.., x . .. . , I.. . /.r n,..... I.. . ,
CA 02551706 2006-06-27
32: Jantan I, Rafi IA, Jalil J.
Platelet-activating factor (PAF) receptor-binding antagonist activity of
Malaysian medicinal
plants.
Phytomedicine. 2005 Jan; 12(1-2):88-92.
PMID: 15693713 [PubMed - indexed for MEDLINE]
33: Mahomoodally MF, Gurib-Fakim A, Subratty AH.
Experimental evidence for in vitro fluid transport in the presence of a
traditional medicinal
fruit extract across rat everted intestinal sacs.
Fundam Clin Pharmacol. 2005 Feb;l9(1):87-92.
PMID: 15660964 [PubMed - indexed for MEDLINE]
34: [No authors listed]
[Bitter melon to control high blood sugar]
Schweiz Rundsch Med Prax. 2004 Dec 8;93(50):2118. German. No abstract
available.
PMID: 15646680 [PubMed - indexed for MEDLINE]
35: Zhuang DH, Ouyang YC, Hu Z.
[Construction of prokaryotic expression vector for MAP30 gene and study of PCR
methods
for rapid identification of recombinant.]
Yi Chuan. 2004 Sep;26(5):701-4. Chinese.
PMID: 15640088 [PubMed - indexed for MEDLINE]
36: Ray SD, Lam TS, Rotollo JA, Phadke S Patel C, Dontabhaktuni A, Mohammad S
Lee H
Strika S, Dobrogowska A, Bruculeri C, Chou A, Patel S Patel R, Manolas T,
Stohs S.
Oxidative stress is the master operator of drug and chemically-induced
programmed and
unprogrammed cell death: Implications of natural antioxidants in vivo.
Biofactors. 2004;21(1-4):223-32.
PMID: 15630201 [PubMed - indexed for MEDLINE]
37: Schmourlo G, Mendonca-Filho RR, Alviano CS, Costa SS.
Screening of antifungal agents using ethanol precipitation and bioautography
of medicinal
and food plants.
J Ethnopharmacol. 2005 Jan 15;96(3):563-8. Epub 2004 Nov 25.
PMID: 15619579 [PubMed - indexed for MEDLINE]
38: Chaturvedi P, George S, Milinganyo M, Tripathi YB.
Effect of Momordica charantia on lipid profile and oral glucose tolerance in
diabetic rats.
Phytother Res. 2004 Nov;18(11):954-6.
PMID: 15597317 [PubMed - indexed for MEDLINE]
47
CA 02551706 2006-06-27
39: Beloin N. Gbeassor M, Akpagana K, Hudson J, de Soussa K. Koumaglo K.
Arnason JT.
Ethnomedicinal uses of Momordicacharantia (Cucurbitaceae) in Togo and relation
to its
phytochemistry and biological activity.
J Ethnopharmacol. 2005 Jan 4;96(1-2):49-55.
PMID: 15588650 [PubMed - indexed for MEDLINE]
40: Senanayake GV, Maruyama M, Sakono M, Fukuda N, Morishita T, Yukizaki C,
Kawano
M, Ohta H.
The effects of bitter melon (Momordica charantia) extracts on serum and liver
lipid
parameters in hamsters fed cholesterol-free and cholesterol-enriched diets.
J Nutr Sci Vitaminol (Tokyo). 2004 Aug;50(4):253-7.
PMID: 15527066 [PubMed - indexed for MEDLINE]
41: Babu PS, Stanely Mainzen Prince P.
Antihyperglycaemic and antioxidant effect of hyponidd, an ayurvedic
herbomineral
formulation in streptozotocin-induced diabetic rats.
J Pharm Pharmacol. 2004 Nov;56(11):1435-42.
PMID: 15525451 [PubMed - indexed for MEDLINE]
42: Sheng Q, Yao H, Xu H, Ling X, He T.
[Isolation of plant insulin from Momordica charantia seeds by gel filtration
and RP-HPLC]
Zhong Yao Cai. 2004 Jun;27(6):414-6. Chinese.
PMID: 15524293 [PubMed - indexed for MEDLINE]
43: Tongia A, Tongia SK, Dave M.
Phytochemical determination and extraction of Momordica charantia fruit and
its
hypoglycemic potentiation of oral hypoglycemic drugs in diabetes mellitus
(NIDDM).
Indian J Physiol Pharmacol. 2004 Apr;48(2):241-4.
PMID: 15521566 [PubMed - indexed for MEDLINE]
44: Jagetia GC. Baliga MS.
The evaluation of nitric oxide scavenging activity of certain Indian medicinal
plants in vitro:
a preliminary study.
J Med Food. 2004 Fall;7(3):343-8.
PMID: 15383230 [PubMed - indexed for MEDLINE]
45: Cummings E. Hundal HS, Wackerhage H. Hope M, Belle M, Adeghate E, Singh J.
Momordica charantia fruit juice stimulates glucose and amino acid uptakes in
L6 myotubes.
Mol Cell Biochem. 2004 Jun;261(1-2):99-104.
PMID: 15362491 [PubMed - indexed for MEDLINE]
48
. .. ... a ..,1 . wY r , . I n !. m , I
CA 02551706 2006-06-27
46: Ahmed I, Adeghate E, Cummings E, Sharma AK, Singh J.
Beneficial effects and mechanism of action of Momordica charantia juice in the
treatment of
streptozotocin-induced diabetes mellitus in rat.
Mol Cell Biochem. 2004 Jun;261(1-2):63-70.
PMID: 15362486 [PubMed - indexed for MEDLINE]
47: Konishi T, Satsu H, Hatsugai Y, Aizawa K, Inakuma T, Nagata S, Sakuda SH,
Na ag sawa
H, Shimizu M.
Inhibitory effect of a bitter melon extract on the P-glycoprotein activity in
intestinal Caco-2
cells.
Br J Pharmacol. 2004 Oct;143(3):379-87. Epub 2004 Sep 6.
PMID: 15351776 [PubMed - indexed for MEDLINE]
48: Kimura K, Numata T, Kakuta Y, Kimura M.
Amino acids conserved at the C-terminal half of the ribonuclease T2 family
contribute to
protein stability of the enzymes.
Biosci Biotechnol Biochem. 2004 Aug;68(8):1748-57.
PMID: 15322360 [PubMed - indexed for MEDLINE]
49: Sultan NA, Maiya BG, Swamy MJ.
Thermodynamic analysis of porphyrin binding to Momordica charantia (bitter
gourd) lectin.
Eur J Biochem. 2004 Aug;271(15):3274-82.
PMID: 15265047 [PubMed - indexed for MEDLINE]
50: Limtrakul P, Khantamat 0, Pintha K.
Inhibition of P-glycoprotein activity and reversal of cancer multidrug
resistance by
Momordica charantia extract.
Cancer Chemother Pharmacol. 2004 Dec;54(6):525-30. Epub 2004 Jul 10.
PMID: 15248030 [PubMed - indexed for MEDLINE]
51: McCarty MF.
Does bitter melon contain an activator of AMP-activated kinase?
Med Hypotheses. 2004;63(2):340-3.
PMID: 15236800 [PubMed - indexed for MEDLINE]
52: RotshteyLi Y, Zito SW.
Application of modified in vitro screening procedure for identifying herbals
possessing
sulfonylurea-like activity.
J Ethnopharmacol. 2004 Aug;93(2-3):337-44.
PMID: 15234774 [PubMed - indexed for MEDLINE]
49
,._...,ti .,. , _ ...a.,..,.....
CA 02551706 2006-06-27
53: Deep G, Dasgupta T, Rao AR, Kale RK.
Cancer preventive potential of Momordica charantia L. against benzo(a)pyrene
induced
fore-stomach tumourigenesis in murine model system.
Indian J Exp Biol. 2004 Mar;42(3):319-22.
PMID: 15233304 [PubMed - indexed for MEDLINE]
54: Prabakar K, Jebanesan A.
Larvicidal efficacy of some Cucurbitacious plant leaf extracts against Culex
quinquefasciatus (Say).
Bioresour Technol. 2004 Oct;95(1):113-4.
PMID: 15207304 [PubMed - indexed for MEDLINE]
55: Grover JK, Yadav SP.
Pharmacological actions and potential uses of Momordica charantia: a review.
J Ethnopharmacol. 2004 Ju1;93(1):123-32. Review.
PMID: 15182917 [PubMed - indexed for MEDLINE]
56 Kohno H, Suzuki R, Yasui Y, Hosokawa M, Miyashita K, Tanaka T.
Pomegranate seed oil rich in conjugated linolenic acid suppresses chemically
induced colon
carcinogenesis in rats.
Cancer Sci. 2004 Jun;95(6):481-6.
PMID: 15182427 [PubMed - indexed for MEDLINE]
57: Kohno H, Yasui Y, Suzuki R, Hosokawa M, Miyashita K, Tanaka T.
Dietary seed oil rich in conjugated linolenic acid from bitter melon inhibits
azoxymethane-
induced rat colon carcinogenesis through elevation of colonic PPARgamma
expression and
alteration of lipid composition.
Int J Cancer. 2004 Ju120;110(6):896-901.
PMID: 15170673 [PubMed - indexed for MEDLINE]
58: Saxena A, Vikram NK.
Role of selected Indian plants in management of type 2 diabetes: a review.
J Altern Complement Med. 2004 Apr;10(2):369-78. Review.
PMID: 15165418 [PubMed - indexed for MEDLINE]
59: Shi M, Cheng R.
[Effects of zinc and boron nutrition on balsam pear (Momordica charantia)
yield and quality,
and polyamines, hormone, and senescence of its leaves]
Ying Yong Sheng Tai Xue Bao. 2004 Jan;15(1):77-80. Chinese.
PMID: 15139192 [PubMed - indexed for MEDLINE]
,,.., . . ... ,,.,..
CA 02551706 2006-06-27
60: Senanayake GV, Maruyama M, Shibuya K, Sakono M, Fukuda N, Morishita T,
Yukizaki C, Kawano M, Ohta H.
effects of bitter melon (Momordica charantia) on serum and liver triglyceride
levels in rats.
hnopharmacol. 2004 Apr;91(2-3):257-62.
OD: 15120448 [PubMed - indexed for MEDLINE]
61: Ichikawa M, Ohta M Kanai S, Yoshida Y, Takano S, Ueoka T, Takahashi T,
Kimoto K,
Funakoshi A. Miyasaka K.
Bitter melon malt vinegar increases daily energy turnover in rats.
J Nutr Sci Vitaminol (Tokyo). 2003 Dec;49(6):428-33.
PMID: 14974734 [PubMed - indexed for MEDLINE]
62: Lu L, Zhao Y.
[Study on hypoglycemic action and active constituents of Momordica charantia
L.]
Zhong Yao Cai. 2002 Jun;25(6):449-5 1. Review. Chinese. No abstract available.
PMID: 14968781 [PubMed - indexed for MEDLINE]
63: Miura T, Itoh Y. Iwamoto N, Kato M, Ishida T.
Suppressive activity of the fruit of Momordica charantia with exercise on
blood glucose in
type 2 diabetic mice.
Biol Pharm Bull. 2004 Feb;27(2):248-50.
PMID: 14758046 [PubMed - indexed for MEDLINE]
64: Mahomoodally MF, Fakim AG, Subratty AH.
Momordica charantia extracts inhibit uptake of monosaccharide and amino acid
across rat
everted gut sacs in-vitro.
Biol Pharm Bull. 2004 Feb;27(2):216-8.
PMID: 14758036 [PubMed - indexed for MEDLINE]
65: Liu X, Li S, Feng C, Yan D.
[Advances in the study of Momordica charantia L.]
Zhong Yao Cai. 2002 Mar;25(3):211-3. Review. Chinese. No abstract available.
PMID: 14748342 [PubMed - indexed for MEDLINE]
66: Manabe M, Takenaka R. Nakasa T, Okinaka O.
Induction of anti-inflammatory responses by dietary Momordica charantia L.
(bitter gourd).
Biosci Biotechnol Biochem. 2003 Dec;67(12):2512-7.
PMID: 14730127 [PubMed - indexed for MEDLINE]
67: Raza H. Ahmed I, John A.
Tissue specific expression and immunohistochemical localization of glutathione
S-
transferase in streptozotocin induced diabetic rats: modulation by Momordica
charantia
(karela) extract.
Life Sci. 2004 Feb 6;74(12):1503-11.
PMID: 14729399 [PubMed - indexed for MEDLINE]
51
. .. .... ,. ,/ .. .n, . . ... . ...i.,... . I..
,CA 02551706 2006-06-27
68: John AJ, Cherian R, Subhash HS, Cherian AM.
Evaluation of the efficacy of bitter gourd (momordica charantia) as an oral
hypoglycemic
agent--a randomized controlled clinical trial.
Indian J Physiol Pharmacol. 2003 Jul;47(3):363-5. No abstract available.
PMID: 14723327 [PubMed - indexed for MEDLINE]
69: Chao CY, Huang CJ.
Bitter gourd (Momordica charantia) extract activates peroxisome proliferator-
activated
receptors and upregulates the expression of the acyl CoA oxidase gene in
H4IIEC3
hepatoma cells.
J Biomed Sci. 2003 Nov-Dec;10(6 Pt 2):782-91.
PMID: 14631118 [PubMed - indexed for MEDLINE]
70: Ou L, Kong LY, Zhang XM, Niwa M.
Oxidation of ferulic acid by Momordica charantia peroxidase and related anti-
inflammation
activity changes.
Biol Pharm Bull. 2003 Nov;26(11):1511-6.
PMID: 14600392 [PubMed - indexed for MEDLINE]
71: Virdi J, Sivakami S, Shahani S, Suthar AC, Banavalikar MM, Biyani MK.
Antihyperglycemic effects of three extracts from Momordica charantia.
J Ethnopharmacol. 2003 Sep;88(1):107-11.
PMID: 12902059 [PubMed - indexed for MEDLINE]
72: Telang M, Srinivasan A, Patankar A, Harsulkar A, Joshi V, Damle A,
Deshpande V,
Sainani M, Ranjekar P, Gupta G, Birah A, Rani S, Kachole M, Giri A, Gupta V.
Bitter gourd proteinase inhibitors: potential growth inhibitors of Helicoverpa
armigera and
Spodoptera litura.
Phytochemistry. 2003 Jul;63 (6):643-52.
PMID: 12842136 [PubMed - indexed for MEDLINE]
73: Tao J, Zhong Z.
[Effects of light on morphological plasticity and biomass allocation of
Momordica
charantia]
Ying Yong Sheng Tai Xue Bao. 2003 Mar;14(3):336-40. Chinese.
PMID: 12836536 [PubMed - indexed for MEDLINE]
74: Pongnikorn S, Fongmoon D, Kasinrerk W, Limtrakul PN.
Effect of bitter melon (Momordica charantia Linn) on level and function of
natural killer
cells in cervical cancer patients with radiotherapy.
J Med Assoc Thai. 2003 Jan;86(1):61-8.
PMID: 12678140 [PubMed - indexed for MEDLINE]
75: Chen Q, Chan LL, Li ET.
52
. . . . . _:. ,... .d. .. .,.. ,.. . . ....I .., l. _.,....,I . .
CA 02551706 2006-06-27
Bitter melon (Momordica charantia) reduces adiposity, lowers serum insulin and
normalizes
glucose tolerance in rats fed a high fat diet.
J Nutr. 2003 Apr;133(4):1088-93.
PMID: 12672924 [PubMed - indexed for MEDLINE]
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78: Grover JK, Rathi SS, Vats V.
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80: De S, Ganguly C, Das S.
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82: Xie H, Huang S, Deng H, Wu Z, Ji A.
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84: Kar A, Choudhary BK, Bandyopadhyay NG.
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85: Rathi SS, Grover JK, Vikrant V, Biswas NR.
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87: Nagasawa H, Watanabe K, Inatomi H.
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98: Wang HX, Ng TB.
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101: Grover JK, Vats V, Rathi SS, Dawar R.
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102: Vikrant V, Grover JK, Tandon N, Rathi SS, Gupta N.
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104: Ahmed I, Lakhani MS, Gillett M, John A, Raza H.
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105: Araba BG.
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106: Murakami T, Emoto A, Matsuda H, Yoshikawa M.
Medicinal foodstuffs. XXI. Structures of new cucurbitane-type triterpene
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triterpene saponins,
goyasaponins I, II, and III, from the fresh fruit of Japanese Momordica
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Chem Pharm Bull (Tokvo). 2001 Jan:49(1):54-63.
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108: Anila L, Vijayalakshmi NR.
Beneficial effects of flavonoids from Sesamum indicum, Emblica officinalis and
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109: Sitasawad SL, Shewade Y, Bhonde R.
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110: Kamei K, Sato S, Hamato N, Takano R, Ohshima K, Yamamoto R, Nishino T,
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Effect of P(2)' site tryptophan and P(20)' site deletion of Momordica
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111: Ja, asooriya AP, Sakono M, Yukizaki C, Kawano M, Yamamoto K, Fukuda N.
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113: Ganguly C, De S, Das S.
Prevention of carcinogen-induced mouse skin papilloma by whole fruit aqueous
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115: Scartezzini P, Speroni E.
Review on some plants of Indian traditional medicine with antioxidant
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116: Lee-Huang S, Huang PL, Sun Y, Chen HC, Kung HF, Huang PL, Murphy WJ.
Inhibition of MDA-MB-231 human breast tumor xenografts and HER2 expression by
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117: Numata T, Kashiba T, Hino M, Funatsu G, Ishiguro M, Yamasaki N, Kimura M.
Expression and mutational analysis of amino acid residues involved in
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118: Ahmad N, Hassan MR, Halder H, Bennoor KS.
Effect of Momordica charantia (Karolla) extracts on fasting and postprandial
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Bangladesh Med Res Counc Bull. 1999 Apr;25(1):11-3.
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Cloning and expression of the Momordica charantia trypsin inhibitor II gene in
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120: Fong WP, Mock WY, Nm TB.
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Modulation of xenobiotic metabolism and oxidative stress in chronic
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The search for natural bioactive compounds through a multidisciplinary
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123: Cahoon EB, Carlson TJ, Ripp KG, Schweiger BJ, Cook GA, Hall SE, Kinney
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124: Valbonesi P, Barbieri L, Bolognesi A, Bonora E, Polito L, Stirpe F.
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125: Zhu Y, Huang Q, Oian M, Jia Y, Tang Y.
Crystal structure of the complex formed between bovine beta-trypsin and MCTI-
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J Protein Chem. 1999 Jul;18(5):505-9.
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126: Schreiber CA, Wan L, Sun Y, Lu L, Krey LC, Lee-Huang S.
The antiviral agents, MAP30 and GAP3 1, are not toxic to human spermatozoa and
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Fertil Steril. 1999 Oct;72(4):686-90.
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127: Yesilada E, Gurbuz I. Shibata H.
Screening of Turkish anti-ulcerogenic folk remedies for anti-Helicobacter
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J Ethnopharmacol. 1999 Sep;66(3):289-93.
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128: Zheng YT, Ben KL, Jin SW.
Alpha-momorcharin inhibits HIV-1 replication in acutely but not chronically
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Zhongguo Yao Li Xue Bao. 1999 Mar;20(3):239-43.
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129: Nakagawa A, Tanaka I. Sakai R, Nakashima T, Funatsu G, Kimura M.
Crystal structure of a ribonuclease from the seeds of bitter gourd (Momordica
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Biochim Bionhvs Acta. 1999 Aus 17:1433(1-2):253-60.
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130: Huang B, Ng TB, Fong WP, Wan CC, Yeung HW.
Isolation of a trypsin inhibitor with deletion of N-terminal pentapeptide from
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Int J Biochem Cell Biol. 1999 Jun;31(6):707-15.
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131: Dhar P, Ghosh S, BhattacharMa DK.
~ Dietary effects of conjugated octadecatrienoic fatty acid (9 cis, 11 trans,
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132: Frame AD, Rios-Olivares E, De Jesus L, Ortiz D, Pagan J, Mendez S.
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133: WangH,NgTB.
Ribosome inactivating protein and lectin from bitter melon (Momordica
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134: Dhar P, Bhattacharyya DK.
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Ann Nutr Metab. 1998;42(5):290-6.
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135: Zambenedetti P, Giordano R, Zatta P.
Histochemical localization of glycoconjugates on microglial cells in
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brain samples by using Abrus precatorius, Maackia amurensis, Momordica
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Exp Neurol. 1998 Sep;153(1):167-71.
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136: Padma P, Komath SS, Swamy MJ.
Fluorescence quenching and time-resolved fluorescence studies on Momordica
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Biochem Mol Biol Int. 1998 Aug;45(5):911-22.
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137: Ahmed I, Adeghate E, Sharma AK, Pallot DJ, Singh J.
Effects of Momordica charantia fruit juice on islet morphology in the pancreas
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Diabetes Res Clin Pract. 1998 Jun;40(3):145-51.
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138: Naseem MZ, Patil SR, Patil SR, Ravindra, Patil RS.
Antispermatogenic and androgenic activities of Momordica charantia (Karela) in
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J Ethnopharmacol. 1998 May;61(1):9-16.
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139: Kusamran WR, Ratanavila A, Tepsuwan A.
Effects of neem flowers, Thai and Chinese bitter gourd fruits and sweet basil
leaves on
hepatic monooxygenases and glutathione S-transferase activities, and in vitro
metabolic
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Food Chem Toxicol. 1998 Jun;36(6):475-84.
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140: Minami Y, Islam MR, Funatsu G.
Chemical modifications of momordin-a and luffin-a, ribosome-inactivating
proteins from
the seeds of Momordica charantia and Luffa cylindrica: involvement of His140,
Tyr165,
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Biosci Biotechnol Biochem. 1998 May;62(5):959-64.
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Observations on ethnoveterinary medicines in Trinidad and Tobago.
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142: Singh A, Singh SP, Bamezai R.
Momordica charantia (Bitter Gourd) peel, pulp, seed and whole fruit extract
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143: Singh A, Singh SP, Bamezai R.
Postnatal efficacy of Momordica charantia peel, pulp, seed and whole fruit
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In Vivo Studies of the Biosynthesis of [alpha] -Eleostearic Acid in the Seed
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Plant Physiol. 1997 Apr;113(4):1343-1349.
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145: Platel K, Srinivasan K.
Plant foods in the management of diabetes mellitus: vegetables as potential
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146: Neumann GM, Condron R, Polya GM.
Purification and sequencing of napin-like protein small and large chains from
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147: Pu Z, Lu BY, Liu WY, Jin SW.
Characterization of the enzymatic mechanism of gamma-momorcharin, a novel
ribosome-
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seeds of bitter
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Biochem Biophys Res Commun. 1996 Dec 4;229(1):287-94.
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148: Omoregbe RE, Ikuebe OM, Ihimire IG.
Antimicrobial activity of some medicinal plants extracts on Escherichia coli,
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Afr J Med Med Sci. 1996 Dec;25(4):373-5.
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149: Raza H, Ahmed I. Lakhani MS, Sharma AK, Pallot D, Montague W.
Effect of bitter melon (Momordica charantia) fruit juice on the hepatic
cytochrome P450-
dependent monooxygenases and glutathione S-transferases in streptozotocin-
induced
diabetic rats.
Biochem Pharmacol. 1996 Nov 22;52(10):1639-42.
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150: Ueno HM, Doyama JT, Padovani CR, Salata E.
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Rev Soc Bras Med Trop. 1996 Sep-Oct;29(5):455-60. Portuguese.
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Screening of medicinal plants for induction of somatic segregation activity in
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152: Komath SS, Nadimpalli SK, Swamy MJ.
Purification in high yield and characterisation of the galactose-specific
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Biochem Mol Biol Int. 1996 May;39(2):243-52.
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153: Bourinbaiar AS, Lee-Huang S.
The activity of plant-derived antiretroviral proteins MAP30 and GAP31 against
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Biochem Biophys Res Commun. 1996 Feb 27;219(3):923-9.
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154: Mock JW, Ng TB, Wong RN, Yao QZ, Yeung HW, Fong WP.
Demonstration of ribonuclease activity in the plant ribosome-inactivating
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155: Basaran AA, Yu TW, Plewa MJ, Anderson D.
An investigation of some Turkish herbal medicines in Salmonella typhimurium
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Teratog Carcinog Mutagen. 1996;16(2):125-38.
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156: Sarkar S, Pranava M, Marita R.
Demonstration of the hypoglycemic action of Momordica charantia in a validated
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model of diabetes.
Pharmacol Res. 1996 Jan;33(1):1-4.
PMID: 8817639 [PubMed - indexed for MEDLINE]
157: Fong WP, Poon YT, Wong TM, Mock JW, Ng TB, Wong RN, Yao QZ, Yeung HW.
A highly efficient procedure for purifying the ribosome-inactivating proteins
alpha- and
beta-momorcharins from Momordica charantia seeds, N-terminal sequence
comparison and
establishment of their N-glycosidase activity.
Life Sci. 1996;59(11):901-9.
PMID: 8795701 [PubMed - indexed for MEDLINE]
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158: Lee-Huang S, Huang PL, Huang PL, Bourinbaiar AS, Chen HC, Kung HF.
Inhibition of the integrase of human immunodeficiency virus (HIV) type 1 by
anti-HIV
plant proteins MAP30 and GAP3 1.
Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8818-22.
PMID: 7568024 [PubMed - indexed for MEDLINE]
159: Lee-Huang S, Huang PL, Chen HC, Huang PL, Bourinbaiar A. Huang HI, Kung
HF.
Anti-HIV and anti-tumor activities of recombinant MAP30 from bitter melon.
Gene. 1995 Aug 19;161(2):151-6.
PMID: 7665070 [PubMed - indexed for MEDLINE]
160: Arai K, Ishima R. Morikawa S, Miyasaka A. Imoto T, Yoshimura S, Aimoto S,
Akasaka
K.
Three-dimensional structure of gurmarin, a sweet taste-suppressing
polypeptide.
J Biomol NMR. 1995 Apr;5(3):297-305.
PMID: 7787425 [PubMed - indexed for MEDLINE]
161:Bourinbaiar AS, Lee-Huang S.
Potentiation of anti-HIV activity of anti-inflammatory drugs, dexamethasone
and
indomethacin, by MAP30, the antiviral agent from bitter melon.
Biochem Biophys Res Commun. 1995 Mar 17;208(2):779-85.
PMID: 7695636 [PubMed - indexed for MEDLINE]
162: Miura S. Funatsu G.
Isolation and amino acid sequences of two trypsin inhibitors from the seeds of
bitter gourd
(Momordica charantia).
Biosci Biotechnol Biochem. 1995 Mar;59(3):469-73.
PMID: 7766185 [PubMed - indexed for MEDLINE]
163: Wu AM, Jiang YJ, Hwang PY, Shen FS.
Characterization of the okra mucilage by interaction with Gal, Ga1NAc and
G1cNAc
specific lectins.
Biochim Biophys Acta. 1995 Feb 23;1243(2):157-60.
PMID: 7873558 [PubMed - indexed for MEDLINE]
164: Hamato N, Koshiba T, Pham TN, Tatsumi Y, Nakamura D, Takano R, Hayashi K,
Hong
YM, Hara S.
Trypsin and elastase inhibitors from bitter gourd (Momordica charantia LINN.)
seeds:
purification, amino acid sequences, and inhibitory activities of four new
inhibitors.
J Biochem (Tokyo). 1995 Feb;117(2):432-7.
PMID: 7608135 [PubMed - indexed for MEDLINE]
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w .. , .. i
CA 02551706 2006-06-27
165: Platel K, Srinivasan K.
Effect of dietary intake of freeze dried bitter gourd (Momordica charantia) in
streptozotocin
induced diabetic rats.
Nahrung. 1995;39(4):262-8.
PMID: 7477242 [PubMed - indexed for MEDLINE]
166: Hayashi K, Takehisa T, Hamato N. Takano R, Hara S, Miyata T. Kato H.
Inhibition of serine proteases of the blood coagulation system by squash
family protease
inhibitors.
J Biochem (Tokyo). 1994 Nov;116(5):1013-18.
PMID: 7896727 [PubMed - indexed for MEDLINE]
167: Tennekoon KH, Jeevatha~paran S. Angunawala P, Karunanayake EH, Jayasinghe
KS.
Effect of Momordica charantia on key hepatic enzymes.
J Ethnopharmacol. 1994 Oct;44(2):93-7.
PMID: 7853870 [PubMed - indexed for MEDLINE]
168: Cakici I Hurmoglu C, Tunctan B, Abacioglu N, Kanzik I. Sener B.
Hypoglycaemic effect of Momordica charantia extracts in normoglycaemic or
cyproheptadine-induced hyperglycaemic mice.
J Ethnopharmacol. 1994 Oct;44(2):117-21.
PMID: 7853862 [PubMed - indexed for MEDLINE]
169: Xiong JP, Xia ZX, Zhang L. Ye GJ, Jin SW. Wang Y.
Crystallization and preliminary crystallographic study of beta-momorcharin.
J Mol Biol. 1994 Apr 29;238(2):284-5.
PMID: 8158655 [PubMed - indexed for MEDLINE]
170: Husain J, Tickle U. Wood SP.
Crystal structure of momordin, a type I ribosome inactivating protein from the
seeds of
Momordica charantia.
FEBS Lett. 1994 Apr 4;342(2):154-8.
PMID: 8143869 [PubMed - indexed for MEDLINE]
171: NgTB, Liu WK, Sze SF, Yeung HW.
Action of alpha-momorcharin, a ribosome inactivating protein, on cultured
tumor cell lines.
Gen Pharmacol. 1994 Jan;25(1):75-7.
PMID: 8026716 [PubMed - indexed for MEDLINE]
172: Ali L, Khan AK Mamun MI, Mosihuzzaman M, Nahar N, Nur-e-Alam M, Rokeya B.
Studies on hypoglycemic effects of fruit pulp, seed, and whole plant of
Momordica
charantia on normal and diabetic model rats.
Planta Med. 1993 Oct;59(5):408-12.
PMID: 8255932 [PubMed - indexed for MEDLINE]
. __.. ,
. . .. . ....,V ..,.. . , ...I.x.r d.-., ..,.~. . .
CA 02551706 2006-06-27
173: Minami Y, Funatsu G.
The complete amino acid sequence of momordin-a, a ribosome-inactivating
protein from
the seeds of bitter gourd (Momordica charantia).
Biosci Biotechnol Biochem. 1993 Ju1;57(7):1141-4.
PMID: 7763984 [PubMed - indexed for MEDLINE]
174: Shibib BA, Khan LA, Rahman R.
Hypoglycaemic activity of Coccinia indica and Momordica charantia in diabetic
rats:
depression of the hepatic gluconeogenic enzymes glucose-6-phosphatase and
fructose-1,6-
bisphosphatase and elevation of both liver and red-cell shunt enzyme glucose-6-
phosphate
dehydrogenase.
Biochem J. 1993 May 15;292 (Pt 1):267-70.
PMID: 8389127 [PubMed - indexed for MEDLINE]
175: Porro G, Bolognesi A, Caretto P, Gromo G, Lento P, Mistza G, Sciumbata T,
Stirpe F,
Modena D.
In vitro and in vivo properties of an anti-CD5-momordin immunotoxin on normal
and
neoplastic T lymphocytes.
Cancer Immunol Immunother. 1993 May;36(5):346-50.
PMID: 7682894 [PubMed - indexed for MEDLINE]
176: Huang Q, Liu S, Tang Y.
Refined 1.6 A resolution crystal structure of the complex formed between
porcine beta-
trypsin and MCTI-A, a trypsin inhibitor of the squash family. Detailed
comparison with
bovine beta-trypsin and its complex.
J Mol Biol. 1993 Feb 20;229(4):1022-36.
PMID: 8445634 [PubMed - indexed for MEDLINE]
177: Platel K, Shurpalekar KS, Srinivasan K.
Influence of bitter gourd (Momordica charantia) on growth and blood
constituents in albino
rats.
Nahrung. 1993;37(2):156-60.
PMID: 8510714 [PubMed - indexed for MEDLINE]
178: De A, Funatsu G.
Crystallization and preliminary X-ray diffraction analysis of a plant
ribonuclease from the
seeds of the bitter gourd Momordica charantia.
J Mol Biol. 1992 Dec 20;228(4):1271-3.
PMID: 1474592 [PubMed - indexed for MEDLINE]
179: Higashino H, Suzuki A, Tanaka Y, Pootakham K.
[Hypoglycemic effects of Siamese Momordica charantia and Phyllanthus urinaria
extracts
in streptozotocin-induced diabetic rats (the 1 st report)]
Nippon Yakurigaku Zasshi. 1992 Nov;100(5):415-21. Japanese.
PMID: 1464400 [PubMed - indexed for MEDLINE]
66
, ... ,
4 ,. . . , d....,
CA 02551706 2006-06-27
180: Battelli MG, Montacuti V, Stirpe F.
High sensitivity of cultured human trophoblasts to ribosome-inactivating
proteins.
Exp Cell Res. 1992 Jul;201(1):109-12.
PMID: 1612115 [PubMed - indexed for MEDLINE]
181: Ng TB, Chan WY, Yeung HW.
Proteins with abortifacient, ribosome inactivating, immunomodulatory,
antitumor and anti-
AIDS activities from Cucurbitaceae plants.
Gen Pharmacol. 1992 Jul;23(4):579-90. Review.
PMID: 1397965 [PubMed - indexed for MEDLINE]
182: Huang_Q, Liu S, Tang Y, Zeng F, Qian R.
Amino acid sequencing of a trypsin inhibitor by refined 1.6 A X-ray crystal
structure of its
complex with porcine beta-trypsin.
FEBS Lett. 1992 Feb 3;297(1-2):143-6.
PMID: 1551419 [PubMed - indexed for MEDLINE]
183: Omi T, Kamesaki T, Kajii E, Ikemoto S.
Method for detecting the lectin activity of Momordica charantia transferred
from micro
two-dimensional electrophoretic gel on to nitrocellulose.
J Chromatogr. 1991 Oct 4;570(2):399-405.
PMID: 1797856 [PubMed - indexed for MEDLINE]
184: Ogata F, Miyata T, Fujii N, Yoshida N, Noda K, Makisumi S, Ito A.
Purification and amino acid sequence of a bitter gourd inhibitor against an
acidic amino
acid-specific endopeptidase of Streptomyces griseus.
J Biol Chem. 1991 Sep 5;266(25):16715-21.
PMID: 1679433 [PubMed - indexed for MEDLINE]
185: Ide H, Kimura M, Arai M, Funatsu G.
The complete amino acid sequence of ribonuclease from the seeds of bitter
gourd
(Momordica charantia).
FEBS Lett. 1991 Sep 2;289(1):126. No abstract available.
PMID: 1894001 [PubMed - indexed for MEDLINE]
186: Giron LM, Freire V, Alonzo A, Caceres A.
Ethnobotanical survey of the medicinal flora used by the Caribs of Guatemala.
J Ethnopharmacol. 1991 Sep;34(2-3):173-87.
PMID: 1795521 [PubMed - indexed for MEDLINE]
187: Kimura Y, Minami Y, Tokuda T, Nakajima S, Takagi S, Funatsu G.
Primary structures of N-linked oligosaccharides of momordin-a, a ribosome-
inactivating
protein from Momordica charantia seeds.
Agric Biol Chem. 1991 Aug;55(8):2031-6.
PMID: 1368729 [PubMed - indexed for MEDLINE]
67
. . . . ... . x ... . .. . ...d. ......CA 02551706 2006-06-27
188: Zafar R, Neerja.
Momordica charantia--a review.
Hamdard Med. 1991 Jul-Sep;34(3):49-61. No abstract available.
PMID: 11613982 [PubMed - indexed for MEDLINE]
189: Yeung HW, Li WW, Ng TB.
Isolation of a ribosome-inactivating and abortifacient protein from seeds of
Luffa
acutangula.
Int J Pept Protein Res. 1991 Ju1;38(1):15-9.
PMID: 1938101 [PubMed - indexed for MEDLINE]
190: Ide H, Kimura M, Arai M, Funatsu G.
The complete amino acid sequence of ribonuclease from the seeds of bitter
gourd
(Momordica charantia).
FEBS Lett. 1991 Jun 24;284(2):161-4. Erratum in: FEBS Lett. 1991 Sep
2;289(1):126.
PMID: 2060635 [PubMed - indexed for MEDLINE]
191: Ho WK, Liu SC, Shaw PC, Yeung HW, Ng TB, Chan WY.
Cloning of the cDNA of alpha-momorcharin: a ribosome inactivating protein.
Biochim Biophys Acta. 1991 Feb 16;1088(2):311-4.
PMID: 2001404 [PubMed - indexed for MEDLINE]
192: Biswas AR, Ramaswamy S, Bgpna JS.
Analgesic effect of Momordica charantia seed extract in mice and rats.
J Ethnopharmacol. 1991 Jan;31(1):115-8. No abstract available.
PMID: 2030591 [PubMed - indexed for MEDLINE]
193: Amorim CZ, Marques AD, Cordeiro RS.
Screening of the antimalarial activity of plants of the Cucurbitaceae family.
Mem Inst Oswaldo Cruz. 1991;86 Supp12:177-80.
PMID: 1841996 [PubMed - indexed for MEDLINE]
194: Lee-Huang S, Huang PL, Nara PL, Chen HC, Kung HF, Huang P, Huang HI,
Huang PL.
MAP 30: a new inhibitor of HIV-1 infection and replication.
FEBS Lett. 1990 Oct 15;272(1-2):12-8.
PMID: 1699801 [PubMed - indexed for MEDLINE]
195: Day C, Cartwright T, Provost J, Bailey CJ.
Hypoglycaemic effect of Momordica charantia extracts.
Planta Med. 1990 Oct;56(5):426-9.
PMID: 2077547 [PubMed - indexed for MEDLINE]
68
CA 02551706 2006-06-27
196: Karunanayake EH, Jeevathayaparan S, Tennekoon KH.
Effect of Momordica charantia fruit juice on streptozotocin-induced diabetes
in rats.
J Ethnopharmacol. 1990 Sep;30(2):199-204.
PMID: 2255210 [PubMed - indexed for MEDLINE]
197: Guevara AP, Lim-Sylianco C, Dayrit F, Finch P.
Antimutagens from Momordica charantia.
Mutat Res. 1990 Jun;230(2):121-6.
PMID: 2115617 [PubMed - indexed for MEDLINE]
198: Cunnick JE, Sakamoto K, Chapes SK, Fortner GW, Takemoto DJ.
Induction of tumor cytotoxic immune cells using a protein from the bitter
melon
(Momordica charantia).
Cell Immunol. 1990 Apr 1;126(2):278-89.
PMID: 2311123 [PubMed - indexed for MEDLINE]
199: Kamesaki T, Omi T, Kajii E, Ikemoto S.
New method of detecting the lectin activity of Momordica charantia.
Vox Sang. 1990;58(4):307-8. No abstract available.
PMID: 2399697 [PubMed - indexed for MEDLINE]
200: Zhu ZJ, Zhong ZC, Luo ZY, Xiao ZY.
[Studies on the active constituents of Momordica charantia L]
Yao Xue Xue Bao. 1990;25(12):898-903. Chinese.
PMID: 2104468 [PubMed - indexed for MEDLINE]
201: Chandrasekar B, Mukherjee B, Mukherjee SK.
Blood sugar lowering potentiality of selected Cucurbitaceae plants of Indian
origin.
Indian J Med Res. 1989 Aug;90:300-5.
PMID: 2620957 [PubMed - indexed for MEDLINE]
202: Singh N, Tyagi SD, Agarwal SC.
Effects of long term feeding of acetone extract of Momordica charantia (whole
fruit
powder) on alloxan diabetic albino rats.
Indian J Physiol Pharmacol. 1989 Apr-Jun;33(2):97-100.
PMID: 2777367 [PubMed - indexed for MEDLINE]
203: Montecucchi PC, Lazzarini AM, Barbieri L, Stirpe F, Soria M, Lappi D.
N-terminal sequence of some ribosome-inactivating proteins.
Int J Pept Protein Res. 1989 Apr;33(4):263-7.
PMID: 2753596 [PubMed - indexed for MEDLINE]
69
...õ. , . ,I
. . - i. ... . . a ~ , _.ti . .
CA 02551706 2006-06-27
204: Hara S, Makino J, Ikenaka T.
Amino acid sequences and disulfide bridges of serine proteinase inhibitors
from bitter
gourd (Momordica charantia LINN.) seeds.
J Biochem (Tokyo). 1989 Jan;105(1):88-91.
PMID: 2738047 [PubMed - indexed for MEDLINE]
205: NgTB, Li WW, Yeung HW.
Effects of lectins with various carbohydrate binding specificities on lipid
metabolism in
isolated rat and hamster adipocytes.
Int J Biochem. 1989;21(2):149-55.
PMID: 2545472 [PubMed - indexed for MEDLINE]
206: Stirpe F, Wawrzynczak EJ, Brown AN, Knyba RE, Watson GJ, Barbieri L,
Thorpe PE.
Selective cytotoxic activity of immunotoxins composed of a monoclonal anti-Thy
1.1
antibody and the ribosome-inactivating proteins bryodin and momordin.
Br J Cancer. 1988 Nov;58(5):558-61.
PMID: 3265330 [PubMed - indexed for MEDLINE]
207: Srivastava Y, Venkatakrishna-Bhatt H, Verma Y.
Effect of Momordica charantia Linn. pomous aqueous extract on cataractogenesis
in murrin
alloxan diabetics.
Pharmacol Res Commun. 1988 Mar;20(3):201-9.
PMID: 3387455 [PubMed - indexed for MEDLINE]
208: Yeung HW, Li WW, Feng Z, Barbieri L, Stirpe F.
Trichosanthin, alpha-momorcharin and beta-momorcharin: identity of
abortifacient and
ribosome-inactivating proteins.
Int J Pept Protein Res. 1988 Mar;31(3):265-8.
PMID: 3372132 [PubMed - indexed for MEDLINE]
209: NgTB, Tam PP, Hon WK, Choi HL, Yeung HW=
Effects of momorcharins on ovarian response to gonadotropin-induced
superovulation in
mice.
Int J Fertil. 1988 Mar-Apr;33(2):123-8.
PMID: 2898450 [PubMed - indexed for MEDLINE]
210: Ng TB, Li WW, Yeung HW.
Effects of ginsenosides, lectins and Momordica charantia insulin-like peptide
on
corticosterone production by isolated rat adrenal cells.
J Ethnopharmacol. 1987 Sep-Oct;21(1):21-9.
PMID: 2826928 [PubMed - indexed for MEDLINE]
, .... ,. .,.... I
. ... ,. 4 ,.,.. I .1.. ,n I,
CA 02551706 2006-06-27
211: Srivastava Y, Venkatakrishna-Bhatt H, Verma Y. Prem AS.
Retardation of retinopathy by Momordica charantia L. (bitter gourd) fruit
extract in alloxan
diabetic rats.
Indian J Exp Biol. 1987 Aug;25(8):571-2. No abstract available.
PMID: 3446597 [PubMed - indexed for MEDLINE]
212: Leung SO, Yeung HW, Leung KN.
The immunosuppressive activities of two abortifacient proteins isolated from
the seeds of
bitter melon (Momordica charantia).
Immunopharmacology. 1987 Jun;13(3):159-71.
PMID: 3497134 [PubMed - indexed for MEDLINE]
213: Ng TB, Wong CM, Li WW, Yeung HW.
Acid-ethanol extractable compounds from fruits and seeds of the bitter gourd
Momordica
charantia: effects on lipid metabolism in isolated rat adipocytes.
Am J Chin Med. 1987;15(1-2):31-42.
PMID: 3318384 [PubMed - indexed for MEDLINE]
214: Ng TB, Wong CM, Li WW, Yeung~HW.
Peptides with antilipolytic and lipogenic activities from seeds of the bitter
gourd
Momordica charantia (family Cucurbitaceae).
Gen Pharmacol. 1987;18(3):275-81.
PMID: 3106137 [PubMed - indexed for MEDLINE]
215: Chan WY, Tam PP, Choi HL, Ng TB, Yeung HW.
Effects of momorcharins on the mouse embryo at the early organogenesis stage.
Contraception. 1986 Nov;34(5):537-44.
PMID: 3816236 [PubMed - indexed for MEDLINE]
216: Welihinda J, Karunanayake EH, SheriffMH, Jayasin e KS.
Effect of Momordica charantia on the glucose tolerance in maturity onset
diabetes.
J Ethnopharmacol. 1986 Sep;17(3):277-82.
PMID: 3807390 [PubMed - indexed for MEDLINE]
217: Welihinda J, Karunanayake EH.
Extra-pancreatic effects of Momordica charantia in rats.
J Ethnopharmacol. 1986 Sep;17(3):247-55.
PMID: 3807387 [PubMed - indexed for MEDLINE]
218: Ng TB, Wong CM, Li WW, Yeung HW.
Isolation and characterization of a galactose binding lectin with
insulinomimetic activities.
From the seeds of the bitter gourd Momordica charantia (Family Cucurbitaceae).
Int J Pept Protein Res. 1986 Aug;28(2):163-72.
PMID: 3533814 [PubMed - indexed for MEDLINE]
71
,. . . _..... .. . ... _ ,
. , 11 ! ....~. r..a n d....õ,,., F, . . .
CA 02551706 2006-06-27
219: Ng TB, Wong CM, Li WW, Yeung HW.
A steryl glycoside fraction from Momordica charantia seeds with an inhibitory
action on
lipid metabolism in vitro.
Biochem Cell Biol. 1986 Aug;64(8):766-71.
PMID: 3021185 [PubMed - indexed for MEDLINE]
220: Ng TB, Wong CM, Li WW, Yeung HW.
Insulin-like molecules in Momordica charantia seeds.
J Ethnopharmacol. 1986 Jan;15(l):107-17.
PMID: 3520153 [PubMed - indexed for MEDLINE]
221: Wong CM, Yeung HW, Ng TB.
Screening of Trichosanthes kirilowii, Momordica charantia and Cucurbita maxima
(family
Cucurbitaceae) for compounds with antilipolytic activity.
J Ethnopharmaco l. 1985 Jul;13 (3 ): 313 -21.
PMID: 4058034 [PubMed - indexed for MEDLINE]
222: Lappi DA, Esch FS, Barbieri L, Stirpe F, Soria M.
Characterization of a Saponaria officinalis seed ribosome-inactivating
protein:
immunoreactivity and sequence homologies.
Biochem Biophys Res Commun. 1985 Jun 28;129(3):934-42.
PMID: 3925952 [PubMed - indexed for MEDLINE]
223: Lei QJ, Jiang XM, Luo AC, Liu ZF, He XC, Wang XD, Cui FY, Chen PX.
Influence of balsam pear (the fruit of Momordica charantia L.) on blood sugar
level.
J Tradit Chin Med. 1985 Jun;5(2):99-106. No abstract available.
PMID: 3851122 [PubMed - indexed for MEDLINE]
224: Bailey CJ, Day C, Turner SL, Leatherdale BA.
Cerasee, a traditional treatment for diabetes. Studies in normal and
streptozotocin diabetic
mice.
Diabetes Res. 1985 Mar;2(2):81-4.
PMID: 3899464 [PubMed - indexed for MEDLINE]
225: Meir P, Yaniv Z.
An in vitro study on the effect of Momordica charantia on glucose uptake and
glucose
metabolism in rats.
Planta Med. 1985 Feb;(1):12-6. No abstract available.
PMID: 4011748 [PubMed - indexed for MEDLINE]
226: Chan WY, Tam PP, So KC, Yeung HW.
The inhibitory effects of beta-momorcharin on endometrial cells in the mouse.
Contraception. 1985 Jan;31(1):83-90.
PMID: 3987275 [PubMed - indexed for MEDLINE]
72
. , . .. Ye...,h .......we.w xNwrMnN=.w ! . ,
CA 02551706 2006-06-27
227: KarunanUa.ke EH, Welihinda J, Sirimanne SR, Sinnadorai G.
Oral hypoglycaemic activity of some medicinal plants of Sri Lanka.
J Ethnopharmacol. 1984 Jul; 11(2):223-3 1.
PMID: 6492834 [PubMed - indexed for MEDLINE]
228: Foxwell B, Long J. Stirpe F.
Cytoxicity of erythrocyte ghosts loaded with ribosome-inactivating proteins
following
fusion with CHO cells.
Biochem Int. 1984 Jun;8(6):811-9.
PMID: 6541045 [PubMed - indexed for MEDLINE]
229: Chan WY, Tam PP, Yeung HW.
The termination of early pregnancy in the mouse by beta-momorcharin.
Contraception. 1984 Jan;29(1):91-100.
PMID: 6734206 [PubMed - indexed for MEDLINE]
230: Jilka C, Strifler B. Fortner GW, Hays EF, Takemoto DJ.
In vivo antitumor activity of the bitter melon (Momordica charantia).
Cancer Res. 1983 Nov;43 (11):5151-5.
PMID: 6616452 [PubMed - indexed for MEDLINE]
231: Sargiacomo M, Barbieri L, Stirpe F, Tomasi M.
Cytotoxicity acquired by ribosome-inactivating proteins carried by
reconstituted Sendai
virus envelopes.
FEBS Lett. 1983 Jun 27;157(1):150-4.
PMID: 6305714 [PubMed - indexed for MEDLINE]
232: Spreafico F, Malfiore C, Moras ML, Marmonti L, Filippeschi S, Barbieri L,
Perocco P.
Stirpe F.
The immunomodulatory activity of the plant proteins Momordica charantia
inhibitor and
pokeweed antiviral protein.
Int J Immunopharmacol. 1983;5(4):335-43.
PMID: 6629594 [PubMed - indexed for MEDLINE]
233: Takemoto DJ, Jilka C, Rockenbach S, Hughes JV.
Purification and characterization of a cytostatic factor with anti-viral
activity from the bitter
melon.
Prep Biochem. 1983;13(4):371-93.
PMID: 6196772 [PubMed - indexed for MEDLINE]
234: Takemoto DJ. Jilka C, Rockenbach S. Hughes JV.
Purification and characterization of a cytostatic factor with anti-viral
activity from the bitter
melon.
Prep Biochem. 1983;13(5):397-421.
PMID: 6142453 [PubMed - indexed for MEDLINE]
73
. . ... .. ~ .i . .11. ...nl x n.na...õ... ,F-
CA 02551706 2006-06-27
235: Falasca A, Gasperi-Campani A, Abbondanza A, Barbieri L, Stirpe F.
Properties of the ribosome-inactivating proteins gelonin, Momordica charantia
inhibitor,
and dianthins.
Biochem J. 1982 Dec 1;207(3):505-9.
PMID: 6819861 [PubMed - indexed for MEDLINE]
236: Farnsworth NR, Waller DP.
Current status of plant products reported to inhibit sperm.
Res Front Fertil Regul. 1982 Jun;2(1):1-16.
PMID: 12179631 [PubMed - indexed for MEDLINE]
237: Akhtar MS.
Trial of Momordica charantia Linn (Karela) powder in patients with maturity-
onset
diabetes.
J Pak Med Assoc. 1982 Apr;32(4):106-7. No abstract available.
PMID: 6806502 [PubMed - indexed for MEDLINE]
238: Kedar P. Chakrabarti CH.
Effects of bittergourd (Momordica charantia) seed & glibenclamide in
streptozotocin
induced diabetes mellitus.
Indian J Exp Biol. 1982 Mar;20(3):232-5. No abstract available.
PMID: 6811427 [PubMed - indexed for MEDLINE]
239: Takemoto DJ, Dunford C, McMurray MM.
The cytotoxic and cytostatic effects of the bitter melon (Momordica charantia)
on human
lymphocytes.
Toxicon. 1982;20(3):593-9.
PMID: 7201686 [PubMed - indexed for MEDLINE]
240: Welihinda J, Arvidson G, Gylfe E, Hellman B, Karlsson E.
The insulin-releasing activity of the tropical plant momordica charantia.
Acta Biol Med Ger. 1982;41(12):1229-40.
PMID: 6765165 [PubMed - indexed for MEDLINE]
241: Foa-Tomasi L, Campadelli-Fiume G, Barbieri L, Stirpe F.
Effect of ribosome-inactivating proteins on virus-infected cells. Inhibition
of virus
multiplication and of protein synthesis.
Arch Virol. 1982;71(4):323-32.
PMID: 6284092 [PubMed - indexed for MEDLINE]
242: Takemoto DJ, Jilka C. Kresie R.
Purification and characterization of a cytostatic factor from the bitter melon
Momordica
charantia.
Prep Biochem. 1982;12(4):355-75.
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