PHYTOTHERAPY RESEARCH. VOL.

7, 285-289 (1993)

Antidiabetic and Adaptogenic Properties of

Momordica charantia Extract: An Experimental
and Clinical Evaluation

Y. Srivastava,*+ H. Venkatakrishna-Bhatt,* Y. Vermat and K. Venkaiah*

t B. J. Medical College and f National Institute of Occupational Health, Ahmedabad 380016, India
B. H. Raval
Alkanand Ayurvedic College, Ahmedabad (Gujarat) India

The hypoglycaemic properties of Mormodicu charuntiu (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 @<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 @<0.01) at the end of the trial but were cumulative and
gradual, unlike that produced by 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.

Keywords: Momordica charantia (bitter gourd) extract; hypoglycaemia; cataract (secondary complication of
diabetes); clinical evaluation.

INTRODUCTION MATERIALS AND METHODS

The commonly practised 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 blind-
ness 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 complica-
tion. 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 vari-
ous authors (Srivastava er 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 concern-
ing 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 a polypeptide (P) (Khanna, 1985). The
present work concerns an experimental and clinical
study to determine whether bitter gourd has any adzp-
togenic effect as reflected in the checking or delaying of
the appearance of cataract, a secondary complication of
diabetes.
Author to whom correspondence should be addressed.
095 1-418X/93/040285-05 $07.50
01993 by John Wiley & Sons, Ltd.
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 ben-
gal gram, 5% shark liver oil in the form of dry mash and
water ad 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 dextr-
ometer before fasting and after 36 h of alloxan treat-
ment. Rats with a blood sugar of 150mg% or more
were included in the diabetic group. Two such rats were
maintained in each cage, under uniform husbandry
conditions. Rats that 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 m L 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 periodi-
cally in diabetic rats for development of cataract (Sri-
vastava 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 dia-
betic diet until the blood sugar was stabilized. Pre and
Accepted (revised) 9 July 1992
286
Table 1. Effect of aqueous extract of Momordica charantia
fruit on blood sugar in diabetic rats
Blood sugar Img%)
Group before treatment
Normal rats 64216
( n = 20)
Control ratsa 275230
( n = 10)
Experimental rats 228242
(n=10)
aTreatment with 2 mL of normal saline.
Duration of treatment was 3 weeks.
post liver function test, kidney function test, haemo-
gram and urine examination were done to determine
any side effects of the herbal treatment.
Preparation of the extract. Bitter gourd (Momordica char-
antia Linn family: Cucarbitaceae) fruit was obtained
fresh locally. An aqueous extract was made by chop-
ping 100 g of fruit and boiling in 200 mL of water until
the volume was reduced to 100mL. 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 haemo-
globin was estimated (Fischer et al., 1980). Besides
these parameters, symptoms such as polyurea, poly-
phagia, 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 summar-
ized in Tables 1-7 The aqueous extract of Momordica
charantia was tested on laboratory animals for the
preliminary confirmation of its hypoglycaemic poten-
tial. 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 220mg% to
105 mg% which is significant (p<O.Ol). The control
group of diabetic rats treated with placebo recorded no
such fall. The results (Table 1) demonstrate the hypo-
glycaemic effect of the herb in rats. A number of
reports have been published claiming a marked hypog-
lycaemic effect of M . charantia extract in laboratory
Table2. Blood and urine sugar levels in clinical trial with
dried powder of Momordica charantia
Blood sugar (rng%)
Case before trial after trial
number PPBS us PPBS
1 297 +++ 154 ++
2 331 ++++ 262 ++
3 280 +++ 21 7 ++
4 424 +++ 377 +++
5 200 +++ 137
PPBS, post prandial blood sugar; US, urine sugar. Dose, 15 g/
subjecvday-5 g thrice a day for a period of 3 weeks.
Y. SRIVASTAVA ET A L
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
after treatment
- tolbutamide. Powdered seeds tested against streptozo-
tocin diabetic rabbits (1-30 &day) produced hypogly-
330228 caemia comparable to tolbutamide (Venkanna-Babu et
al., 1988). Normal as well as diabetic rabbits when
105k40 treated with the fruit of M . charantia recorded a fall in
blood sugar (Yakub, 1980). Mormodica 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 a more potent hypoglycaemic than tolbuta-
mide given in equivalent doses. The result suggested a
pancreatic as well as an extrapancreatic action of char-
antia (Ng et d., 1986; Welihinda et d., 1986; Welihinda
and Karunanayake, 1986).
Our confirmatory study in laboratory animals was
followed by a clinical trial. The first 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
1OOg of the fruit in a 100mL volume in a single
standard dose in the morning. A variation in the prep-
aration was tried to determine differences in the hypo-
glycaemic 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 sugar
was 25% of the initial level, however, statistically it is
insignificant. Table 3 shows the results of the aqueous
extract trial. The subjects included were severe
(433mg%) to mild (260%) diabetics, aged 42 to 70
years, all males. Blood sugar was estimated after 2 , 3 , 4
and 7 weeks of treatment. 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<O.Ol) as against 25% observed
in the powder treated group. Further the aqueous
extract treated diabetics showed a time-related 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 45.8k13.6 mg%
in juvenile and maturity onset diabetics as well as in
Fall in
chemical diabetes. N o hypersensitivity reaction was
blood sugar noticed (Baldwa et al., 1987). It was found effective
us (Yo) through the oral route (Khanna, 1985). Polypeptide-P
48.0 obtained from the fruit seed and cultured M . charantia
20.8 cells produced hypoglycaemia in maturity onset as well
22.5
as juvenile diabetics. Now fruits of M. charantia are
11.0
reported to have hypoglycaemic effects in clinical trials
+ 31.5
with mildly diabetic patients. Blood glucose reduction
by seeds was comparable to glybenclamide. Its extra-
pancreatic (Welihinda and Karunanayake, 1986) as
 ANTIDIABETIC PROPERTIES OF M . CHARANTIA 287

Table3. Blood and urine sugar levels in clinical trial with aqueous extract of Momordica
churantiu
Case
Length of number Blood sugar (PPBS, mg%)
treatment 6 7 8 9 10 11 12
0 weeks 422 236 380 280 380 450 250
a++++ ++ ++++ +++ +++ +++ ++
2 weeks 200 170 191 225 200 191 175
++ + ++ ++ + ++ ++
3 weeks 142 151 - 180 160 150 140
trace nil + trace + nil
4 weeks 120 110 120 150 125 115 120
nil nil nil nil nil nil nil
7 weeks 97 99 118 - - 100 115
nil nil nil nil nil nil nil
Wrine sugar, qualitative.

Table 4. Glycosylated haemoglobin before and after the clini- Table6. Period of appearance of cataract in drug treated
cal trial diabetic rats and diabetic control rats
Glycosylated haemoglobin (mg%) Blood sugar (mg%l
mean+SD range after alloxan after Period of cata-
Diabetic Group Initial treatment 2 months ract development
before treatment 8.37k0.39 (8.0-9.0) Diabetic 64+16 290k44 305f61 93f16 days
Diabetic control
after treatment 6.95k0.46a (6.2-7.6) ( n = 10)
Diabetic 60+15 270k40 109+66' 146k30' days
*p<O.Ol,n=7.
treated (NS) (NS)
( n = 10)

well as pancreatic activity has been reported in rats and NS, Non significant (compared with control).
aSignificant pcO.01.
cats respectively (Lolitkar and Rajaram-Rao, 1962;
1966). Three nonsteroidal hypoglycaemic principles
have been isolated, from unripened fruits of bitter Simultaneously with blood sugar, a qualitative urine
gourd, different from the earlier reported principles, sugar level examination was carried out. Other trials
and named as kakra l b , kakra l l l a and kakra l l l b but with aqueous extract also showed an absence of sugar
their chemistry is unknown as yet. Kakra l b has been in urine when blood sugar registered within normal
reported to act by suppressing free fatty acid levels. limits. Urine sugar estimation was done just before and
Hypoglycaemic effects were evident in the glucose after a gap in the treatment of these subjects. The
tolerance test. Our findings are in agreement with the results expressed in Table 7 show that the sugar appears
earlier reports regarding hypoglycaemia caused by M. in urine in the absence of treatment but to a much
charantia. So far most workers have tried to isolate lesser extent compared with the initial urine sugar
active principles of the fruit, administered orally or by levels. This indicates that the reversal of the control of
injection (as is the case for insulin or oral hypoglycae- diabetes is not total and immediate, unlike other con-
mics) compared in terms of a reduction of blood sugar ventional treatments practised.
after a given number of hours. From the animal experi- Table 4 shows the levels of glycosylated haemoglobin
ments we found the response to aqueous extract of M. in patients before and after the clinical trial. The rate of
charantia fruit increased over a number of days of glycosylation is proportional to the concentration of
treatment indicating a time-related cumulative res- blood glucose (Cerami et al., 1979; Monnier and
ponse. Hence in the clinical trial, the blood sugar level Cerami, 1982). Blood sugar at the peak of the glucose
was monitored after 2, 3, 4 and 7 weeks until the level tolerance curve correlates with glycosylation (Koeing et
stabilized or returned to normal limits. In almost all al., 1976) and with the improvement glycaemic control,
cases it returned to normal limits. None of the earlier glycosylation of haemoglobin also decreases. Hence
published reports on M. charantia followed our criteria estimation of glycosylated haemoglobin is a well-
or an exactly similar plan of work. accepted parameter useful in the management and
prognosis of the disease (Bunn et al., 1978; Stevans et
al., 1977; Koeing et al., 1977; Chang and Noble, 1979).
Table5 Hypoglycaemia caused by powder of dried fruit of
Momordica charantia and aqueous extract
Length of Overall fall in blood Table 7. Urine sugar after gap in therapy
Preparation Dose trial sugar (PPBS) (%I
Initial Urine sugar Gap in Urine sugar
Powder of 15 glsubjectlday 3 weeks 25 Case blood sugar Urine after clinical therapy after gap
dried fruit in 3 equal doses number (mg%) sugar trial (days1 in therapy
of 5 g each 6 422 ++++ nil 1 +
Aqueous 100 g/100mL of 3 weeks 54 7 236 ++ nil 1 nil
extract of water, single 8 380 +++ nil 2 +
fruit standard dose 9 280 ++ nil 1 +
288 Y.SRIVASTAVA ET A L
The initial level of haemoglobin glycosylation in dia-
betic subjects in the present study was 8.37k0.4. 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 a f . , 1981). In in
uiuo and in uitro studies of the crystalline lens, it was
observed that glycosylated lens proteins cross-link by
disulphide bonds to form high molecular weight form-
ing aggregates which display opalescence in solution
similar to that observed in diabetic cataract (Monnier
and Cerami, 1982; Srivastava et a f . , 1987a, b). There is
clinical recognition of cataract as a diabetic complica-
tion. Its incidence and severity increases with the
advancement of diabetes. Of the groups of alloxan
diabetic rats one was used as control and the other was
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