Pakistan Journal of Pharmacology

Vol.25, No.1, January 2008, pp.7-12

CLINICAL INVESTIGATION OF HYPOGLYCEMIC EFFECT

OF UNRIPE FRUIT ON MOMORDICA CHARANTIA
IN TYPE-2 (NIDDM) DIABETES MELLITUS
AKBAR WAHEED, G.A. MIANA*, TARIQ SHARAFATULLAH**
AND S.I. AHMAD***
Department of Pharmacology & Therapeutics Army Medical College Rawalpindi
*Riphah Institute of Pharmaceutical Sciences Islamabad
**Department of Pharmacology, Sindh Medical College, Karachi
***Dr. HMI Institute of Herbal Medicine and Pharmacology Hamdard University, Karachi

ABSTRACT
The present study was designed to investigate clinically the hypoglycemic effect of
unripe fruit of Momordica charantia in Type-2 diabetes mellitus. After assaying fasting
plasma and urinary glucose, 10 patients of type-2 diabetes mellitus with no previous
medication, 10 patients of type-2 diabetes mellitus taking oral hypoglycemic agents with
history of inadequate control and six control subjects were given low (0.5 g/kg/d in two
divided doses) and high (1.5 g/kg/d in two divided doses) doses of powdered part,
aqueous extract and alcoholic extract of unripe fruit of Momordica charantia for 14 days.
15th day blood and urine samples for glucose were taken. Based on results obtained it was
found that Momordica charantia has significant hypoglycemic activity and can be given
to type-2 diabetic patients with no previous medication alone or in combination to
patients taking oral hypoglycemic agents with inadequate control of blood glucose both
in low or high doses depending upon their plasma glucose concentration.

INTRODUCTION gourd roots paste in combination with equal

The bitter gourd is a common vegetable
cultivated extensively in tropical areas
including Mica, Asia, Caribbean, South
America and Subcontinent. Being a relatively
common food item, the bitter gourd was
traditionally used for a dazzling array of
conditions by people in tropical regions.
Numerous infections, cancer and diabetes are
among the most common conditions it was
reported to improve (Duke, 1985).
The leaves and fruit have both been used
occasionally to make tea and beer or to season
soups in the western world. The berries also
produces wax, which can be used to made
candles. Juice of fresh leaves is valuable in
piles. A paste of the roots can also be applied
over piles with beneficial result. Bitter gourd
with lime-juice is highly beneficial in
treatment of disorders like boils, scabies
ringworm and other fungal diseases. Bitter
part of honey taken regularly is beneficial for
asthma, bronchitis, pharyngitis, rhinitis etc.
Fresh juice of leaves (2 teaspoonful) mixed
with equal quantity of white onion juice and
lime-juice is effective in diarrhoea (Raman and
Lau 1996).
MATERIALS AND METHODS
The present study was carried out in the
laboratories of Hamdard Institute of
Pharmaceutical Sciences, Islamabad and Army
Medical College, Rawalpindi. The following
criteria was used to include or exclude the
patients in the study.
Inclusion Criteria
1. Type 2 diabetic patients with fasting
plasma glucose level equal to or greater
than 140 mg/dl (WHO study group on
diabetes mellitus, 1985, Geneva technical
report series 727) without any
8 Clinical Investigation of Hypoglycemic Effect of Urinary Glucose M. Charantia
detectable/visible complications (WHO,
1985).
2. Type 2 diabetic patients taking oral
hypoglycemic agents with history of
inadequate control of blood glucose with
these agents.
3. Normal healthy subjects with no family
history of diabetes mellitus.
4. The patients and control subjects were of
either sex (male or female) between the
ages of 35-60 years.
Exclusion Criteria
1. Pregnant or nursing patients.
2. Smokers
3. Patients with GIT, hepatic, cardiovascular,
renal or endocrine disorder (other than
diabetes mellitus) which can interfere with
the absorption, metabolism and excretion
of the study plant.
4. Patients with any complication of diabetes
mellitus.
5. Patients suffering from type 1 (IDDM)
diabetes mellitus.
Subjects
The selected subjects (patients and controls)
were medically examined and given code
numbers and were asked to present themselves
on a specified date for sample collection. They
were requested to come with fasting (no food
before 12 hours) and to void their morning
urine and to drink 250ml water before coming
for testing (Bahajiri et al., 2000). Patients
already taking oral hypoglycemic agents were
requested to take their usual medicine and
food after sampling.
Blood Sample
Blood samples (3-5 ml) were drawn from each
patient and control subject by venepuncture
through plastic disposable syringes. The blood
samples were collected in clean oven dried
glass bottles which were previously rinsed
with 1% sodium fluoride, 3% potassium
oxalate solution to prevent coagulation and
glycolysis. The plasma was separated after
centrifugation. Any sample showing
haemolysis was discarded. After separation of
plasma, it was transferred to clean, previously
acid rinsed, washed and oven dried glass
bottles with plastic caps. The plasma glucose
estimation was done immediately on the same
day by kit method (Trinder, 1969).
Plant
Momordica charantia unripe fruits were
obtained from the local area. Dr. Mir Ajab
Khan department of biological sciences Quaid-
i-Azam University Islamabad identified the
fruits of selected plant. The unripe fruits were
shade dried, pulverized by a mechanical
grinder and passed through 40-mesh sieve.
Filtrate from powdered samples of leaves
soaked overnight in 95% ethanol and distilled
water, were used as alcoholic and aqueous
extract respectively for studied plant (Ahmed
et al., 1995).
Aqueous Extract
After grinding in an electric grinder, the
powder was soaked in equal amount of water
and stirred intermittently and then left
overnight. The macerated pulp was then
filtered through a coarse sieve and the filtrate
was dried at reduced temperature. This dry
mass served as aqueous extract of plant for
experimentation (Vats et al., 2002).
Alcoholic Extract
Alcoholic extract was prepared by
powdering I kg plant material in an electric
grinder. The powder was then mixed with 500
ml of alcohol and kept at room temperature for
36 hours. The slurry was stirred intermittently
for 2 hours and left overnight. The mixture
was then filtered and the filtrate was freed
from solvent under partial vacuum (71 mmHg)
at 35-45oC to yield pulp. A few drops of
silicon emulsion were added near the end of
distillation to avoid frothing. The final residue
collected was a thick paste. This was dried at
reduced temperature. This dried mass served
as alcoholic extract for experimentation (Vats
et al., 2002).
General Plan of Study
The fasting blood and urine samples from
patients and control subjects were assayed for
respective glucose levels. 10 patients of type 2
Akbarwaheed et al.
diabetes mellitus with no previous medication
and 10 type-2 diabetic patients taking oral
hypoglycemic agents (with history of
inadequate control) were given dry powdered
unripe fruits of Momordica charantia for
fourteen days. On 15th day blood and urine
samples of glucose were taken.
After an interval of one-week fasting
blood and urine samples were again taken
from these patients. These patients were given
aqueous extract of Momordica charantia
unripe fruits for 14 days. On 15th day, blood
and urinary samples of glucose were taken.
After an interval of one-week fasting blood
and urine samples for the monitoring of
glucose level were again taken from these
patients. These patients were given alcoholic
extract of the Momordica charantia fruits for
14 days. On 15th day blood and urinary
samples of glucose were taken. Out of the ten
patients five received low dose (0.5 g/kg/d in
two divided doses) and five received high dose
(1.5 g/kg/d in two divided doses) of the plant.
Six healthy subjects were kept as control.
Three subjects received low dose and three
subjects received high dose of powdered,
aqueous and alcoholic extracts of unripe fruits
of Momordica charantia as described above.
All the patients and control subjects were
monitored for any adverse reaction of the
extract. Plasma assay of glucose was done by
kit method and urinary glucose was estimated
by strip method (Burtis et al., 1998). The data
was statistically evaluated (Glazer, 2001).
RESULTS
The results are summarized in the
following table and graph.
Untoward Effects
GIT upsets e.g., nausea, abdominal
discomfort (with high dose), vomiting was
reported on administration of first high dose of
Momordica charantia (4 patients, 80%). Mild
headache initially was complained by some
patients belonging to all groups. The basis of
9
headache was psychological. Symptoms of
mild hypoglycemia e.g., feeling of hunger,
apprehension, sweating, yawning were
reported by only two patients (40%) taking
chlorpropamide and glyburide respectively
with high dose of Momordica charantia but
these symptoms disappeared on adjusting the
diets of these patients accordingly.
DISCUSSION
Diabetes mellitus has been defined as a
syndrome of abnormal carbohydrate
metabolism, resulting in hyperglycemia with
acute metabolic complications and chronic
vascular, neurogenic and orthopedic
complications affecting many organs of the
body.
There was a significant decrease in mean
concentration of plasma glucose two weeks
after administration of both low (0.5 gm/kg)
and high (1.5 gm/kg) dose of powdered part,
aqueous extract and alcoholic extract of fruits
of Momordica charantia in type-2 diabetic
patients. There was a marked fall in mean
value of plasma glucose with high dose of fruit
of Momordica charantia as compared to that
of low dose. The mean value of plasma
glucose was in the normal controlled range of
diabetes mellitus (although at upper limit of
normal with low dose). Glycosuria
disappeared two weeks after administration of
both low and high dose of fruit of Momordica
charantia.
These results were correlated with the
following studies:
In one study the treatment of streptozocin
diabetic rats with Momordica charantia fruit
extract over a period of 10 weeks returned
high blood glucose levels to normal (Ahmed et
al., 2001). In other study, in the streptozocin
diabetic rats, Momordica charantia improved
the oral glucose tolerance causing significant
reduction in plasma glucose to 26% at 3.5
hour. Momordica charantia extract (500
mg/kg) caused a 4-5 fold increase in the rate of
glycogen synthesis from 4-14 C-glucose in the
10 Clinical Investigation of Hypoglycemic Effect of Urinary Glucose M. Charantia

Table
Table showing effects of dry powdered part, aqueous extract and alcoholic extract of Unripe
fruit of Momordica charantia on blood and urinary glucose in type-2 diabetic patients with no
previous medication, taking oral hypoglycemic agents with history of inadequate control and
control subjects before and two weeks after administration. The values are given as Mean SD
(n=l0+l0+6)

Blood glucose (mg/dl) Urinary Glucose

Before After Before After
Administration Administration Administration Administration
Dry Powdered Part
No previous medication
Low dose 209 14.31 134.8 4.65* Glycosuria No. Glycosuria
High dose 207.5 17.46 106 18.50* Glycosuria No. Glycosuria
Taking oral hypoglycemics
Low dose 157 11.83 130.8 4.14* No. Glycosuria No. Glycosuria
High dose 163.6 10.35 92 12.04* No. Glycosuria No. Glycosuria
Control
Low dose 70 75 NS No. Glycosuria No. Glycosuria
High dose 75 78 NS No. Glycosuria No. Glycosuria
Aqueous Extract
No previous medication
Low dose 198.6 10.59 133.4 3.36* Glycosuria No. Glycosuria
High dose 206.2 13.34 112.4 14.02* Glycosuria No. Glycosuria
Taking oral hypoglycemics
Low dose 156 10.48 125.6 9.09* No. Glycosuria No. Glycosuria
High dose 159.2 12.89 91.2 11.81* No. Glycosuria No. Glycosuria
Control
Low dose 80 75 NS No. Glycosuria No. Glycosuria
High dose 95 82 NS No. Glycosuria No. Glycosuria
Alcoholic Extract
No previous medication
Low dose 206 9.48 137 2.54* Glycosuria No. Glycosuria
High dose 207.8 11.18 116.6 9.83* Glycosuria No. Glycosuria
Taking oral hypoglycemics
Low dose 153.2 8.48 117.8 16.58* No. Glycosuria No. Glycosuria
High dose 161.8 12.69 119.2 11.18* No. Glycosuria No. Glycosuria
Control
Low dose 66 14 NS No. Glycosuria No. Glycosuria
High dose 70 72 NS No. Glycosuria No. Glycosuria
Low dose: 0.5 g/kg in two divided doses High dose: 1.5 g/kg in two divided doses
*Significant NS: Non significant

liver of normally fed rats (Sarkar et al., 1996).
Lininger et al. (1998) have recommended
that a small bitter gourd (Momordica
charantia) can be eaten as food or upto 50 ml
of fresh juice can be drunk per day or 5 ml bid
or tid per day for lowering the blood glucose
levels. Rahman and Zaman, (1989), in their
review article have reported the anti-diabetic
effect of Momordica charantia (fruit). The
activity of BF (bitter fruit/bitter gourd) juice
was tested on STZ treated RIN (Rat
insulinoma) cells and isolated islets in vitro. It
was found that feeding with BF juice caused
reduction in STZ-induced hyperglycaemia in
mice. It also reduced the STZ-induced
apoptosis in RIN cells indicating the mode of
protection of BF juice on RIN cells, islets and
pancreatic beta-cells (Sitaswad et al., 2000).
Investigations were carried out to evaluate
the effect of Momordica charantia on the
Akbarwaheed et al. 11

250

207.8
206.2
198.6
209

206

201
200

163.6

161.8
159.2

153.2
157

156
134.8

133.4
130.8

125.6

137

119.2
117.8
116.6
150

112.4
106

91.2
92
100

76
76
50

0
L H L H L H L H L H L H Control

N M O H A N M O H A N M O H A

Dry Powdered Part Aqueous Extract Alcoholic Extract

Before Administration After Administration

L = Low Dose H = High Dose N M = Patients taking No Medication

OHA = Patients taking Oral Hypoglycemic Agents

Graph: Comparison of effect on blood glucose in type-2 diabetic patients and control subjects
before and two weeks after administration of dry powder part, aqueous and alcoholic extract of
unripe fruit of Momordica charantia.

glucose tolerance of maturity onset diabetic fruit include a mixture of steroidal saponins as
patients. The fruit juice of Momordica charantin, insulin like peptides and alkaloids
charantia was found to significantly improve (Lininger et al., 1998). All of the above
the glucose tolerance of 73% of the patients mentioned studies indicate that the antidiabetic
investigated while 27% failed to respond16. In effect of Momordica charantia is due to:
another study the juice or tablets from the
powder of the fruits of Momordica charantia Increased utilization of glucose in the
showed significant blood glucose lowering liver.
effect on patients and the infusion of the drug Insulin like activity.
and crude crystalline substance showed same Inhibit glucose absorption.
effect (Khan, 2000). Acts as insulin secretagoue.
Steroidal glycosides, insulinomimetic
Mechanism of Action
lectins and alkaloids are responsible for
In a study the long term administration
hypoglycemic and anti-hyperglycaemic effect
(10 weeks, orally) of Momordica charantia
of Momordica charantia (Raman and Lau
fruit extract to normal and streptozocin (STZ)
1996).
induced type-I diabetic rats, returned the blood
glucose and lipid profile levels to normal CONCLUSION
(Ahmed et al., 2001). The Momordica
charantia is said to contain a insulin like Momordica charantia has significant
hypoglycemic principle, plant insulin, which is hypoglycemic activity and can be given to
highly beneficial in lowering the blood sugar type-2 diabetic patients with no previous
levels (Bakhru, 2000). Momordica charantia medication alone or in combination to patients
12 Clinical Investigation of Hypoglycemic Effect of Urinary Glucose M. Charantia
taking oral hypoglycemic agents with
inadequate control of blood glucose both in
low or high doses depending upon their
plasma glucose concentration.
REFERENCES
Ahmed, I., Lakhani, M.S., Gillet, M., John, A.
and Raza, H. (2001). Hypotriglyceridemic
and hypocholesterolemic effects of
antidiabetic Momordica charantia
(Karela) fruit extract in streptozocin
induced diabetic rats. Diabetes Res. Clin.
Pract., 51(3): 155-161.
Ahmed, M., Ismail, N. and Ismail, Z. (1995).
Pharmacognostic profile of Trigonella
seed and its hypoglycaemic activity.
Natural Product Sciences, 1(1): 25-30.
Bahajiri, S.M., Mirza, S.A, Mufti, AM. and
Ajabnoor, M.A. (2000). The effects of
inorganic chromium and brewers yeast
supplementation on glucose tolerance,
serum lipids and drug dosage in
individuals with type-2 diabetes. Saudi
Med J., 21(9): 831-837.
Bakhru, H.K. (2000). Foods that heal (16th
printing). Orient Paperback, a division of
Vision Book Pvt. Ltd, India, pp.65-68.
Burtis, C.A and Ashwood, E.R. (Editors).
(1998). Tietz textbook of clinical
chemistry, 3rd Ed, Indira Printers, New
Delhi, India (W.B. Saunders Co. and
Harcourt Brace & Co. Asia Ptv. Ltd.),
p.783.
Duke, J.J. (1985). Hand book of medicinal
herbs. Boca Raton, FL., CRC Press
London: 315-316.
Glazer, A N. (2001). High-YieldTM Bio-
statistics. Williams & Wilkins, Phila-
delphia, USA, pp.19-44.
Jamil, M., Amin, Z., Chaudhry, T.H., Shaheen,
J. and Mi, Z.R. (2001). Management of
diabetic foot infections. JCPSP; 11(10):
6060-6610.
Khan, M.T.H. (2000). Diabetes mellitus.
Treatment and complications. Hamdard
Medicus. XLIII, 3: 71-83.
Lininger, S., Wright, J., Austin, S., Brown, D.
and Gaby., A. (1998). The Natural
pharmacy. Prime health. A division of
Prima Publishing, USA, pp.39-44.
Raman, A, Lau, C. (1996). Anti-diabetic
properties and phytochemistry of Momo-
rdica charantia L. (Curcurbitaceae).
Phyto. Med. Res., 2: 349-62.
Rehman, A. and Zaman, K. (1989). Medicinal
plants with hypoglycaemic activity. J.
Ethnopharmacol., 26: 1-55.
Sarkar, S., Pramava, M. and Marita, R. (1996).
Demonstration of the hypoglycaemic
action of Momordica charantia in a
validated animal model of diabetes.
Pharmacol. Res., 33(1): 1-4.
Sitaswad, S.L., Shewad, Y. and Bhonde, R.
(2000). Role of bitter gourd fruit juice in
STZ induced diabetic state in vivo and in
vitro. J. Ethno. Pharmacol., 73(1-2): 71-
79.
Trinder, P. (1969). Enzymatic determination of
plasma glucose. Ann. Clin. Biochem., 6:
24.
Vats V., Grover IK. and Rathi S.S. (2002).
Evaluation of anti-hyperglycemic and
hypoglycemic effect of Trigonella
foenum-graecum Linn, Ocimum sanctum
Linn and Pterocarpus marsupium Linn in
normal and alloxanized diabetic rats. J.
Ethno-Pharmaool., 79: 95-100.
Welihinda, J., Kayunanayake, E.H., Sherif,
M.H. and Jayasinghe, K.S. (1986). Effect
of Momordica charantia on the glucose
tolerance in maturity onset diabetes. J.
Ethnopharmacol., 17(3): 277-282.
World Health Organization (1985). Diabetes
mellitus, report of study group. Geneva:
WHO technical report series; 727.