Momordica charantia Linn.

(Family: Cucurbitaceae)
Chemistry & Pharmacology
Author: William D. Torres, Ph. D.
Type of Publication: Review
Date of Publication: Unpublished
Notes: Dr. Torres was Director of the Philippines Bureau of Food and Drugs (19992002). He Finished M.S. in Pharmacognosy and Ph.D. in Biopharmaceutics at the
University of Mississippi, U.S.A.
I.

Introduction
Plants have been used for the treatment of diseases throughout the
world since the beginning of the civilization. Among these plants is
Momordica charantia Linn. of the cucurbitaceae family. Hundreds of
scientific papers have been published describing the chemistry and
pharmacology of M. charantia (MC). This paper will try to integrate the
findings of these papers and to provide a better understanding of the
growing use of this plant to alleviate the dreadful effects of diabetes,
whether Type I or Type II.
Traditionally the fruits, seeds and leaves are used as an anti-diabetic
agent. In India where the plant is better known as Karela, it is used as a
tonic, emetic and laxative (1). Traditional Chinese medicine includes uses
for the fruits, leaves and seeds in gastroenteritis, diabetes, tumors and
some viral infections (2). This paper will try to focus on the anti-diabetic
properties of MC by identifying the phytochemical constituents and, if
possible, to correlate these constituents with the pharmacologic effects
observed.
Briefly, MC (58) is a monoecious herbaceous vine with bright green,
lobed leaves and numerous, small fragrant flowers. Mature fruits of the
wild balsam pear (MC) are 2-7cm in length and 1.4-2cm in width. They
are ovoid to oblong, pointed at both ends, and are covered with small
warts and have a8-10 irregular longitudinal ridges marked by prominent
triangular tubercles. The green soft pericarp turns orange an eventually
red with age. At maturity, the three valves of the dehiscent fruit curl back
to expose 5-20 seeds, each surrounded by a scarlet, sticky, pulpy aril.
Seeds are 5-9mm long and are slightly three-toothed at the apex and
base; the sculptured faces are regulose and pale brown with irregular
black areas and corrugated black margins.

II.

Phytochemistry
Momordica charantia Linn. (Ampalaya, Bitter Gourd, Karela, Bitter
Melon) has been shown to have a variety of chemical constitutuents. A
petroleum ether extract (1) of the dried and powdered whole plant
provided a highly volatile aromatic ethereal oil, fixed oil, free fatty acids,
cholesterin and carotene. After exhaustion with petroleum ether, the dried
material was macerated with ether. The ether extract provided the
pigment cyanophyll and xanthophylls, resins, glucosids and an alkaloid.
The alcoholic extract that followed the ether extraction provided further
proof of the presence of a glucoside. In 1962 Lotikar and Rao (4) isolated
from the fruits of MC a non-nitrogenous substance identified as a
charantin. It is a whitish crystalline material melting at 266-268 C with
decomposition. Gamma-aminobutyric acid was also isolated by Durand et
1

al. (5) from MC. Baldwa et al. (8) isolated an insulin-like compound from
the fruits and tissue cultures of M. charantia L. this plant insulin has 17
amino acids in two chains bound together with sulfide bonds. The infra-red
spectrum was super imposable of that on standard zinc crystalline bovine
insulin. This plant insulin is stable at 4C and is denatured by heat. Two
storage proteins have been isolated and purified from seeds of MC. (11)
these proteins contain a very high concentration of glutamic acid plus
glutamine and arginine. The ripe fruit and leaves provide a guanyulat
cyclase inhibitor with an estimated molecular weight of 5,000 to 50,000
estimated by gel filtration and is acid stable and heat labile. In 1978, Lin
et al. (12) reported the isolation of lectins; proteins that can agglutinate
blood cells, from the seeds of MC. Molecular weights of 23,678 and 31,762
were determined by gel electrophoresis. The same lectins were isolated
and purified by Li (16). Charantin, isolated by Lotikar and Rao (4) was
later found by Sucrow (56) in 1965 to be a mixture of sitosteryl-3-DGlucoside
and
5,25-stigmastadiene-3-ol
D-Glucoside.
Additional
compounds were isolated and identified by Ulubelen and Sankawa (13) in
1979 from the tissue cultures of the unripe fruits of MC. These are
diosgenen -sitosterol, 7-stigmasten-ol, 5-stigmasten-3, 25 diol, 5,25stigmastadiene-3-ol and 7,25-stigmastadiene-3-ol. The leaves yielded
additional compounds such as n-octacosans (C28H58), triacontanol
(C30H62O) and a new phytosphingosin (structure to be established). The
group of Okabe (15) isolated two triterpene glycosides, momordicosides A
and B, from the seeds on M. charantia L. Structures were shown as the 2O--gentiobioside
and
3-O--D-xylopyranosyl
of
cucurbit-5-ene3,22(s),13(R),25-pentaol.
Three
triterpene
glycosides
named
momordicosides C, D and E were isolated from the seeds of MC by
Miyahara et al. (18). The structures were determined as 3-O-gentiobiosides of cucurbit-5ene-3,23,24,25-tetraol; cucurbita-5,24 diene3,22,23, triol and 3-hydroxy-23,24,25,26,27-penanor-20()-cucurbiten-22-al, respectively. Iyer et al. (21) isolated from the immature seeds of
MC two cytokinins G1 and G2 that were identified as zeatin riboside and
zeatin, respectively. These cytokinins are intimately involved in the
physiological processes associated with seed and fruit development. Dutta
et al. (22) reported the isolation and structure elucidation of a glycoside of
a non-protein nitrogenous base, vicine, from the seeds of MC, which in
the presence of other factors is a favism-inducing toxin. The aglycone
could not be isolated as such. In 1981, Khanna et al. (26) isolated from
the fruit seeds and tissue of MC a hypoglycemic peptide, polypeptide-p,
which has a minimum molecular weight of approximately 11,000 (166
residues). This appears to be similar to the plant-insulin isolated by
Baldwa et al. (9). Fatty acids were also isolated and studied (57). A
cytostatic factor was purified and characterized by Takamoto et al. (58).
This was derived from the crude aqueous extract of the whole ripe fruit.
The factor is tentatively identified as a 11,00 dalton protein. Further works
by Okabe at al. (28) on the immature fruits of MC provided two bitter
cucurbitacins, momordicosides K and L, and four non-bitter
momordicosides F1, F2, G and I. These are triterpenes with no oxygen
function at C11. Momordicosides F1, F2, G and I are the first cucurbitacins
having
Cgformyl
and
7-0--D-glucopepanosyl
groups.
Among
momordicosides, G and F2 are the first members of cucurbitacin having Dallose as a component sugar. The full structure of bitter
glycosidesmomordicosides K and L were previously elucidated by Okabe et
2

al. (29) T.B. Ng et al. (35) isolated, through extraction and processing of
MC seeds using the method which was developed originally for the
purification of insect and annelid insulins, insulin-like molecules. A
galactose binding lectin with insulinomimetric activities was isolated from
the seeds of bitter gourd (36). The lectin had a molecular weight of
124,000 and approximately has a 5% carbohydrate content. The
molecular weight of the subunits was 37,000, 35,000 and 33,000. The
same authors (37) isolated a saponin fraction from MC seeds. This fraction
provided a sterol glycoside with an inhibitory action on lipid metabolism in
vitro. Using seeds of MC, which were stored for half a year after
harvesting, Kikuchi et al (35), isolated eight and identified six triterpene
alcohols, as 10-cucurbita-5, 24-dien-3-ol, taraxerol, -amyrin,
cycloartenol,
24-methylinecycloartanol,
and
multiflorenol.
Two
abortifacient proteins designated as and momorcharins were isolated
from seeds of the bitter gourd by Young et al. (39). The two proteins were
approximately equipotent in inducing midterm abortion in mice. In a study
where decorticated seeds of MC were extracted with acidic ethanol, Ng et
al. (42) isolated two peptides with antilipolytic and lipogenic activities.
Mixtures of acylglucosylsterols were isolated from the green fruits of MC
and the structures elucidated by Guevara et al. (45).
The major
acylglucosylsterol
was
3-O-[6O-palmitoyl--D-glucosyl]-stigmasta5,25(27)-diene. In 1990, Lee-Huang et al. (59) isolated and purified from
the seeds and fruits of MC a new inhibitor of human immuno-deficiency
virus (HIV). This compound MAP 30 is a basic protein of about 30,000
daltons. The sequence of the N-terminal 44 amino acids has been
determined. Takeda et al. (46) isolated from the leaves of MC three new
cucurbitane triterpenoids (compounds 1, 3 and 6). Together with two
other known compounds. Compound 1 has a molecular formula of
C36H60O83/2H2O. cp[art 3 is C30H48O4H2O and copart 6 is C31H50O43/2H2O.
Vicine, a hypoglycemic glycol-alkaloid was obtained from the defatted
seeds of MC by Handa et al. (48). It is reported as similar to the active
principle of Vicia fava responsible for the acute hemolytic crises known as
favism. The structure has been shown as 2,6-diminopyrimidinol-5--Dglucopyramoside. A ribonuclease was isolated from the seeds of bitter
gourd by Ide et al. (60). The protein contains 191 amino acid residues and
has a calculated molecular mass of 21,259 Daltons (Da). Since MC is a
widely cultivated plant for medicinal and food uses, Yuwai et al. (49)
analyzed the chemical composition of the fruit. This study was conducted
to determine the levels of lipids, fatty acids, protein, amino acids, and
minerals in bitter gourd. Results indicated that the fruits of bitter gourd
contained nutritionally useful quantities of most of the essential minerals
and amno acids. The predominant fatty acid was -eleostearic acid in nopolar lipids, linolenic acid in glycolipids, and palmitic acid in phospholipids.
Ribosome-inactivating proteins were isolated from the seeds of bitter
gourd (69). These proteins were identified as momordin-a and momordinb (molecular masses estimated to be 29,400 Da) and differ in
carbohydrate contents. Three trypsin inhibitors (MCTI-A,-B,_C0) were
purified from the bitter gourd seeds (61). The primary and spatial
structures were determined by x-ray crystallography. They appear to be
similar to the squash family proteinase inhibitors. Many cucurbitane-type
triterpene glycosides have been isolated from bitter gourd or goya in
Japan, but the constituents responsible for the inhibition of glucose
absorption have not been identified. Murakami et al. (62) isolated and
3

identified eight new cucurbitane-type triterpene glycosides and three new

oleanane-type saponins from the fresh fruits of goya. These were
goyaglycosides-A,-B,-C,-D,-E,-F,-G and H, and goyasaponins I, II, and
III. These compounds are to be used in the studies of bioactive
constituents of medicinal foodstuff 9food supplements).
To summarize, the phytochemicals of MC ranges from alkaloids,
glyvosides, peptides, acids, cucurbitins, momordine, momorcharins,
proteins, steroidal glycosides, vices, p-insulin, zeatin riboside, etc.
III.

Pharmacology
MC is used primarily as an alternative therapy for diabetes. Bitter
melon has a long history of use as a hypoglycemic agent in Asia, Africa
and Latin America. Data from in vitro and limited in vivo studies do
support folkloric use of this plant. Extracts, teas and powdered
formulations of the stems, leaves and fruits are used. The plant is also
consumed as a foodstuff. This review will present and describe the
many studies on the pharmacology of MC with brief discussions on
clinical efficacy, adverse effects, and drug interactions to determine the
appropriate place of bitter melon in therapy.
Multiple mechanisms have been proposed as the cause of bitter
melons hypoglycemic property. Some research works support the
insulin-like activity of MC. Others propose a decrease in hepatic
gluconegenesis, or increase hepatic glycogen synthesis or an increased
peripheral glucose oxidation in erythrocytes and adipocytes, or an
increase pancreatic insulin secretion through increased beta-cell
production in the pancreas.
Rivera (1) cited the use of M. charantia L. in the Philippines as
reported by Tavera et al. (2). He also pointed out the empirical use in
Puerto Rico of cundeamor (MC) for the treatment of diabetes
mellitus. Sharma et al. (2) used the juice of the karela fruit (MC) in
determining glucose tolerance of rabbits, rats with alloxan-induced
diabetes. Normal rabbits and rats were used as control. Effects of a
single dose of karela juice (6 cc/kg) appeared to be optimal with a
maximal fall in blood sugar level seen after 2 hour in normal rabbits
and starts rising from 3 hours onwards. In diabetic rabbits, however,
the blood sugar continues to fall up to 4 hours and then starts rising.
No such activity was found in rats. The fruit extract appears to be an
abortifacient in rats. Lotlikar and Rao (4) demonstrated the
hypoglycemic activity of charantin, a whitish crystalline material
isolated from the fresh dried fruits of M. charantia L. Results indicated
that charantin, a non-nitrogenous neural principle is capable of
producing prolonged hypoglycemia activity of charantin in
depancreatized cats is less, but not abolished, indicating a pancreatic
as well a extra-pancreatic action. Baldwa et al. (9) administered to
nine diabetic patients the insulin-like compound isolated from the fruits
and tissue cultures of MC. It showed a consistent hypoglycemic effect
with an average fall in blood sugar level that is statistically significant.
The onset of the action was within 30-60 minutes and with peak effect
six hours after administration. Using the fruit extract (seeds removed)
of MC, Leatherdale et al. showed improved glucose tolerance in nine
non-insulin dependent diabetics and six non-diabetic laboratory rats.
Results of experiments conducted by Akhar et al. (20) demonstrated
that the fruit of MC possessed a significant and consistent

hypoglycemic effect in normal and alloxan-diabetic rabbits. They

further suggested that probably MC contains more than one type of
hypoglycemic
principles.
Khanna
et al. (23), administered
subcutaneously to human patients insulin they isolated from the fruits,
seeds and tissue culture of MC. A significant blood sugar lowering
effect was observed. The peak effect in the juvenile diabetic may be
between 4-8 hours compared to 2 hours for bovine insulin. The peak
response in maternity-onset diabetics is not as readily determined.
Blood sugar levels in streptozotocin-induced diabetes mellitus in
rabbits was monitored after administering powdered seeds of MC or
glibenclamide. All levels of bityter gourd seed were at par with
glibenclamide in hypoglycemic activity (34). The probable mechanism
is stimulation of insulin production. This was further shown by
Welihinda et al. (40). An aqueaous solution from the unripe fruits was
found to be a potent stimulator of insulin release from -cell-rich
pancreatic islets isolated from obesehyperglycemic mic.e the
stimulation of insulin release was partially reversible. Bailey et al. (34)
also demonstrated the hypoglycemic effect of concentrated extracts of
MC in streptozotocin diabtic mice. Welihinda et al. (40) in another
investigation found the fruit juice of MC to significantly improve the
glucose tolerance of 73% of the patients with maturity onset diabetes.
This study gives scientific validity to the use of MC as an oral
hypoglycemic agent by traditional medical practitioners. Tiangda et al.
(43) demonstrated the hypoglycemic activity of the water-chloroform
extract of unripe fruits of MC in normal and alloxan-induced diabetic
rbbits. The blood glucose level showed significant decrease at 10 and
20 mg/kg i.v.
A number of research works also indicated that MC extract
exhibits other pharmacological and toxicological properties. These are
presented in a review reported by Rau et al. (63).
IV.

Conclusion
In summary, Momordica charantia L. fruits, leaves, seeds and other parts,
when used as dry powders, extracts, decoctions, fresh or cooled, has
clearly demonstrated hypoglycemic activity both in vitro and in vivo.
Animal studies, cell cultures, and small-scale clinical reports have all
demonstrated the beneficial effects of adding MC to the established
medicinal regimen for controlling the adverse effects of diabetes mellitus.
MC has been in use for thousands of years as food and traditional
medicine with more reported beneficial effects than adverse events. In
response to a wealth of new research information, attitudes and
perceptions on the use of MC as a food supplement to aid in the control of
diabetes mellitus should be more acceptable. Many benefits have been
identified such as increasing glucose tolerance (23,26,34,35,40) and
potentiates insulin and other anti-diabetic drugs (25,40). Although these
positive effects have not always been observed in every circumstance, no
known situations or studies have demonstrated any negative effects
associated with supplemental use of MC when done correctly. Studies have
proved that the supplemental use of MC instead of predisposing diabetics
to the many adverse effects of uncontrolled blood sugar levels can be used
as an alternative to decrease morbidity and mortality. While supplemental
use of MC is no silver bullet, it should be viewed as a medicinal
management tool that is readily available to diabetic patients.

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