Antidiabetic and Adaptogenic Properties of Momordica
charantia Extract: An Experimental and Clinical
Evaluation
Author: Y. Srivastava, H. Venkatakrishna-Bhatt, Y. Verma, K. Venkaiah
Type of Publication: Pre-clinical
Date of Publication: 1993
Publication: Phytotherapy Research, Vol. 7, pp 285-289, 1993
Organization: B.J. Medical College and National Institute of Occupational Health
Abstract: The hypoglycaemic properties of Momordica charantia (bitter gourd) water
extract was tested on alloxan diabetic rats experimentally. A fall of blood sugar after
3 week’s treatment with aqueous extract of fruits of the herb was found to be
significant (p<0.01). The aqueous extract of fruit was more effective in diabetes (fall
of blood sugar 54% after 3 week’s therapy) than the powder of the dried fruit (fall
25% nonsignificant). Hypoglycaemic effects in diabetic patients were found to be
highly significant (p>0.01) at the end of the trial but were cumulative and gradual,
unlike that produced bu insulin. Adaptogenic properties are indicated by the delay in
the appearance of cataracts, the secondary complications of diabetes and relief in
neurological and other common symptoms even before the hypoglycaemia occurred
INTRODUCTION
The commonly practiced treatment of diabetes includes oral antidiabetics and/or
insulin injections. Insulin can maintain blood glucose within a normal range but
cannot simulate the pancreas of a healthy individual. Hence, diabetics within 15 to
20 years of diagnosis begin to develop complications (Engerman et al., 1977).
Diabetes is the leading cause of noncongenital blindness among adults aged 20 to 70
years, the leading cause of kidney failure, it doubles the risk of heart disease,
gangrene of the extremities and there is a clinical recognition of cataract as a
diabetic complication. The range of these complications is directly related to the
hour-to-hour fluctuations in blood sugar that persist even when insulin is taken once
or twice a day (Job et al., 1975; Piters et al., 1975). Certain Indian plants have
antidiabetic properties as reported by various authors (Srivastava et al., 1983, 1985)
such as hypoglycaemic agents (Srivastava et al., 1986; 1988) and retardation of
retinopathy (Srivastava et al., 1987a, b). A number of reports have appeared
concerning the hypoglycaemic properties of the fruit and seed of the bitter gourd
(Bildwa et al., 1977; Yaqub, 1980; Padminikadar and Chakrabarthi, 1982; Khanna,
1985; Ng et al., 1986; Welihinda et al., 1986). The bitter fruit variety is reported to
be more effective in diabetes (Satyavati et al., 1987). The fruit and seed showed the
presence of the polypeptide (P) (Khanna, 1985). The present work concerns an
experimental and clinical study to determine whether bitter gourd has any
adaptogenic effect as reflected in the checking or delaying of the appearance of
cataract, a secondary complications of diabetes.
MATERIALS AND METHODS
Pharmacological studies. The experimental part of this study was carried out with
Charles Foster rats, of both sexes weighing 150-200 g reared on standard
laboratory, diet containing 70% cracked wheat, 20% cracked bengal gram, 5% shark
liver oil n the form of dry mash and water adaptogenic libitum. A freshly prepared
solution of alloxan in normal saline was injected subcutaneously (120 mg/ kg body
wt.) to overnight fasted rats. Blood samples were drawn from the caudal vein by the
pinch clip method. Blood sugar was estimated using a dextrometer before fasting
and after 36 hr of allxan treatment. Rats with a blood sugar of 150 mg% or more
were included in the diabetic group. Two such rats were maintained in each cage,
under uniform husbandry conditions.
Rats died during the experiment were
excluded. A dose response curve was produced. From studies, 4 g of bitter gourd
fruit was found to yield optimum results, the period of treatment being 3 weeks. An
aqueous extract of 4 g of fruit was given per rat in 2 mL volumes by oral intubation.
Diabetic rats included in the control group were administered 2 mL of placebo. Blood
sugar, fundus, lenticular opacity and apparent signs and symptoms were examined
periodically in diabetic rats for development of cataract (Srivastava et al., 1987a, b).
Clinical study. The clinical part of this study was carried out on diabetic patients
after confirmation by oral glucose tolerance test of postprandial blood sugar (PPBS)
according to the criteria of the World Health Organization. The subjects were
maintained on a diabetic diet until the blood sugar was stabilized. Pre and post liver
function test, kidney function test, haemogram and urine examination were done to
determine any side effects of the herbal treatment.
Preparation of the extract. Bitter gourd (Momordica charantia Linn family:
Cucurbitaceae) fruit was obtained fresh locally. An aqueous extract was made by
chopping 100 g of fruit and boiling 200 mL of water until the volume was reduced to
100 mL. The chips were then smashed and the decoction was filtered with muslin
cloth. The aqueous extract thus prepared was given as a standard single dose in the
morning. The other set of diabetic patients were given powder of dried fruit, 15 g
(equivalent to 100 g wet weight) thrice a day in equal doses of 5 g each.
Glycosylated haemoglobin was estimated (Fischer et al., 1980). Besides these
parameters, symptoms such as polyurea, polyphagia, burning in the hands and feet,
pain in calf muscles and generalized weakness were observed before and after the
trial.
RESULTS AND DISCUSSION
The results of the present investigations are summarized in Tables 1-7. The aqueous
extract of Momordica charantia was tested on laboratory animals for the preliminary
confirmation of its hypoglycaemic potential.
The diabetic group of animals
administered 2 mL of aqueous extract for a period of 3 weeks showed a reduction of
the initial blood sugar from 220 mg% to 105 mg% which is significant (p<0.01).
The control group of diabetic rats treated with placebo recorded no such fall. The
results (Table 1) demonstrate the hypoglycaemic effect of the herb in rats. A
number of reports have been published claimng a marked hypoglycaemic effect of M.
charantia extract in laboratory animals, in normal as well diabetic animals (Sharma
et al., 1960). The ether extract of the residue of the alcohol extract from leaves of
M. charantia was reported to have hypoglycaemic activity comparable to
tolbutamide. Powdered seeds tested against streptozotocin diabetic rabbits (1-30
g/day) produced hypoglycaemia comparable to tolbutamide (Venkanna-Babu et al.,
1988). Normal as well as diabetic rabbits when treated with the fruit of M. charantia
recorded a fall in blood sugar (Yakub, 1980). Momordica charantia extract showed
the highest hypoglycaemic effect when tried on diabetes recovered rabbits
(Venkanna-Babu et al., 1988). Charantin isolated from M. charantia fruit is a
hypoglycaemic in normal and fasting rabbits. It was found to be more potent
hypoglycaemic than tolbutamide given in equivalent doses. The result suggested a
pancreatic as well as an extrapancreatic action of charantia (Ng et al., 1986;
Welihinda, et al., 1986; Welihinda and Karunanayake, 1986).
Our confirmatory study in laboratory animals was followed by a clinical trial.
The group of diabetic patients was given powder of sun-dried fruit of M. charantia
three times a day (5 g each time, and 15 g in total). The second group was given
aqueous extract of 100 g of the fruit in a 100 mL volume in a single standard dose in
the morning. A variation in the preparation was tried to determine differences in the
hypoglycaemic effect of these preparations.
Table 2 shows the results of the clinical trial with patients administered
powder of M. charantia dried fruit concluded within 21 days. The fall in blood
sugarwas 25% of the initial level, however, statistically it is insignificant. Table 3
shows the result of the aqueous extract trial. The subjects included were severe
(433 mg %) to mild (260% diabetics, aged 42 to 70 years, all males. Blood sugar
was estimated after 2, 3, 4 and 7 weeks of treatmen. The fall in blood sugar was
highly significant at the termination of treatment. The response was overwhelming
when compared with hypoglycaemia caused by the powder of M. charantia (Table 5)
after an initial period of 3 weeks of therapy. The fall in blood sugar in aqueous
extract treated diabetics was 54.0% (p<0.01) as against 25% observed in the
powder treated group. Further the aqueous extract treated diabetics showed a timerelated gradual hypoglycaemic response as revealed in blood sugar and urine sugar
data obtained at 2, 3, 4 and 7 weeks. This feature of the herbal treatment of
diabetes is unlike conventional treatment. In almost all cases the blood sugar level
was restored within the normal limits.
The pure protein known as P-insulin or polypeptide-P extracted from M.
charantia fruit in crystalline form was tested in controlled clinical trials for its efficacy
as an hypoglycaemic agent. When administered s.c. it produced a mean fall in blood
sugar of 45.8  13.6 mg% in juvenile and maturity onset diabetics as well as in
chemical diabetes. No hypersensitivity reaction was noticed (Baldwa et al., 1987).
It was found effective through the oral route (Khanna, 1985). Pollypeptide-P
obtained from the fruit seed and cultured M. charantia cells produced hypoglycaemia
in maturity onset as well as juvenile diabetics. Now fruits of M. charantia are
reported to have hypoglycaemic effects in clinical trials with mildly diabetic patients.
Blood glucose reduction by seeds was comparable to glybenclamide.
Its
extrapancreatic (Welihinda and Karunanayake, 1986) as well as pancreatic activity
has been reported in rats and cats respectively (Lolitkar and Rajaram-Rao, 1962;
1966). Three non-steroidal hypoglycaemic principles have been isolated, from
unripened fruits of bitter gourd, different from the earlier reported principles, and
named as kakra 1b, kakra 111a and kakra 111b but their chemistry is unknown as
yet. Kakra 1b has been reported to act by suppressing free fatty acid levels.
Hypoglycaemic effects were evident in the glucose tolerance test. Our findings are in
agreement with the earlier reports regarding hypoglycaemia caused by M. charantia.
So far most workers have tried to isolate active principles of the fruit, administered
orally or by injection (as is the case for insulin or oral hypoglycaemics) compared in
terms of reduction of blood sugar after a given number of hours. From the animal
experiments we found the response to aqueous extract of M. charantia fruit
increased over a number of days of treatment indicating a time-related cumulative
response. Hence in the clinical trial, the blood sugar level was monitored after 2, 3,
4 and 7 weeks until the level stabilized or returned to normal limits. In almost all
cases it returned to normal limits. None of the earlier published reports on M.
charantia followed our criteria or an exactly similar plan of work.
Simultaneously with blood sugar, a qualitative urine sugar level examination
was carried out. Other trials with aqueous extract also showed an absence of sugar
in urine when blood sugar registered within normal limits. Urine sugar estimation
was done just before and after a gap in the treatment of these subjects. The results
expressed in Table 7 show that the sugar appears in urine in the absence of
treatment but to a much lesser extent compared with the initial urine sugar levels.
This indicates that the reversal of the control of diabetes is not total and immediate,
unlike other conventional treatments practised.
Table 4 shows the levels of glycosylated haemoglobin in patients before and
after the clinical trial. The rate of glycosylation is proportional to the concentration
of blood glucose (Cerami et al., 1979; Monnier and Cerami, 1982). Blood sugar at
the peak of the glucose tolerance curve correlates with glycosylation (Koeing et al,
1976) and with the improvement glycaemic control, glycosylation of haemoglobin
also decreases. Hence, estimation of glycosylated haemoglobin is a well-accepted
parameter useful in the management and prognosis of the disease (Bunn et al.,
1978; Stevans et al., 1977; Koeing et al., 1977; Chang nad Noble, 1979). The initial
level of haemoglobin glycosylation in diabetic subjects in the present study was
8.37 0.4. The value was reduced to 6.1 after the control of glycaemia. This finding
is in agreement with earlier reports.
Under normal physiological conditions glucose can react nonenzymatically
with proteins to form covalent adducts which form brown fluorescent pigments. In
diabetes, this takes place at an accelerated rate causing structural and functional
changes in physiologically active proteins leading to pathogenesis and diabetic
complications, viz., neuropathy (Cerami et al., 1979) and neuropathic changes
(Vlassora et al., 1981). In in vivo and in vitro studies of the crystalline lens, it was
observed that glycosylated lens proteins cross-link by disulphide bonds to form high
molecular weight forming aggregates which display opalescence in solution similar to
that observed in diabetic cataract (Monnier and Cerami, 1982; Srivastava et al.,
1987a, b). There is clinical recognition of cataract as a diabetic complication. Its
incidence and severity increases with the advancement of diabetes. Of the groups of
alloxan diabetic rats one was used as control and other was treated with the aqueous
extract of bitter gourd fruit for 2 months. The average period of appearance of
apparent sugar cataract in the control group was 3 months, while in the treated
group it was 5 months.
The delay in the cataract formation was significant
(p<0.01). The results are presented in Table 6. It gives some indications of the
adaptogenic properties of the herb, since herbs are know to have many principlec
anatagonistic and synergistic to each other but their combined result produces the
desired effect.
The aqueous extract of M. charantia seems to induce a better adaptation
against diabetes with control of glycaemia as reflected by a delay in the appearance
of cataract. An inability to totally reverse glycosuria is evidenced by the gap in the
treatment and the relief in symptoms such as polyphagia, polydipsia, burnng in
hands and feet, pain in calf muscle and generalized weakness at a stage of treatment
before the control of hyperglycaemia. A hypothesis regarding the mode of action
needs further study since the hypoglycaemic properties of this herb cannot be
attributed to a single principle.
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