Antihyperglycemic Status of Coccinia grandis: An Extensive Overview
Betsy Sunny1*, Dr. Manju Maria Mathews2, Dhanish Joseph3, Flowerlet Mathew4, Junia George5, Bimi Varghese6
1,5,6Department of Pharmaceutics, Nirmala College of Pharmacy, Muvattupuzha, Kerala
2Associate Professor, Department of Pharmaceutics, Nirmala College of Pharmacy, Muvattupuzha, Kerala
3,4Assistant Professor, Department of Pharmaceutics, Nirmala College of Pharmacy, Muvattupuzha, Kerala
*Corresponding Author E-mail: betsysunnye@gmail.com
ABSTRACT:
Plants are an exemplary source of medicine and have been used in healthcare since time immemorial. They are an efficacious remedy for multiple ailments. Coccinia grandis belonging to family Cucurbitaceae is a reservoir of medicinal properties. It is being regarded as a universal panacea in Ayurvedic medicines. Extracts made from the various parts of the plant mainly leaf and fruit have significant analgesic, anti-inflammatory, antimicrobial, antidiabetic, antioxidant, hepatoprotective, anticancer, mutagenic activity, etc. in different animal models. Coccinia grandis contain copious amounts of phytoconstituents like flavonoids, saponins, glycosides, alkaloids, phenols, etc. which heavily contribute to the diverse pharmacological activities. In this study, the focus is given to Coccinia grandis as a better herbal substitute for synthetic counterparts in antihyperglycemic therapy.
KEYWORDS: Coccinia grandis, Cucurbitaceae, ayurvedic medicine, animal models, antihyperglycemic.
INTRODUCTION:
It is a climbing, herbaceous, branched tropical vine native to tropical Asia, including India. Being a part of Indian traditional medicine for ages, it has been widely utilized in reducing blood sugar among other varied uses. The intention of this study is to discuss and sum up on the numerous literature reported with the antihyperglycemic potency of Coccinia grandis (CG).
METHODOLOGY:
Literature regarding the antidiabetic efficacy of CG have been collected from diverse databases, thoroughly analyzed and arrived into conclusions.
Botanical Description:
CG is a dioecious, perennial and herbaceous climber with glabrous stems and tuberous roots. This plant possesses axillary tendrils long-lived scrambling or climbing vine grows up to 13m in height and can form a very dense cover over vegetation. When stems of CG touch soil, they strike roots readily at the nodes. Initially, younger stems are slender, green, and smooth but as they grow they become swollen and semi-succulent in nature.
Leaves are alternate and simple. The alternately arranged leaves are borne on stalks 1-3cm long and coiled tendrils are often produced in their forks.
Table No.1 Phytochemicals present in various parts of Coccinia grandis 6,7,8
|
Leaves |
β-Sitosterol, Cephalandrol, Cephalandrine A & B, Heptacosane, Alkaloids, Carbohydrate, Proteins, Amino acids,Tannins, Saponins, Flavonoids, Phytosterol, Triterpenes |
|
Fruits |
β- Amyrin Acetate, Lupeol, Cucurbitacin B, Taraxerone, Taraxerol, β-carotene, Lycopene, Cryptoxanthin, Xyloglucan, Carotenoids, β-sitosterol, Stigma-7-en-3-one, Pectin, Riboflavin, Niacin, Ascorbic acid 15 |
|
Roots |
Resin, Alkaloids, Starch, Fatty Acids, Carbonic acid, Triterpenoid, Flavonoid -Glycoside, Lupeol, β-amyrin, β-sitosterol, Taraxerol |
|
Aerial parts |
Heptacosane, Cephalandrol, β -sitosterol, Alkaloids, Cephalandrins A and B |
|
Whole plant |
Aspartic acid, Glutamic Acid, Asparagine, Tyrosine, Histidine, Phenylalanine, Threonine, Valine, Arginine |
|
Seeds |
The seeds contain fat and fixed oil which are mainly esters of linoleic, oleic and palmitic acids |
These lobed leaves are somewhat ivy-shaped in nature (3.5-9cm long and 4-9cm wide) and usually have tiny teeth spaced along their margins. The tendrils are long, elastic with a coil-like springy character that will wrap around the host to the whole length. This species produces separate male as well as female flowers on separate plants. These white, tubular, flowers are borne singly in the leaf forks on stalks 1-5cm long. They have five tiny slender sepals (6-8mm long) that are joined along at the base and frequently have five spreading petal lobes with pointed tips. In the short tube at the center of the male flowers are three convoluted stamens, while the center of the female flowers usually bears three hairy stigmas. Fruit of the plant belongs to berry type: oval and hairless with thick and sticky skin. The raw fruit is green in color resembles a small dark green cucumber with paler stripes. These fleshy fruit (2.5-6cm long and up to 3.5cm wide) turn bright scarlet red as they mature and contains several pale, flattened seeds. Two varieties of CG are recognized; tender fruits are bitter in one variety and not bitter in other, and the latter is used in Asian cooking. Morphologically no difference is evident between them, however; both varieties are invasive and are found to grow close to each other.5
CG is rich in secondary metabolites such as phenolic compounds and alkaloids. The phytochemicals of this plant include saponins, flavonoids, glycosides, xyloglucan, taraxerol, carotenoids, and cryptoxanthin. Saponins in combination with phytochemicals can provide high anti-diabetic activity, as shown in various other instances. They are widely distributed plant metabolites which can be isolated from the leaf extracts of C. grandis. The existence of flavonoids adds value to this herb since they are a group of compounds which are known to exhibit antioxidant, and thereby, anti-diabetic activities. The antioxidant activity of C. grandis is hypothesized to be exerted through its reducing power, hydrogen peroxide scavenging potential owing to the existence of flavonoids. It has also shown an α-amylase inhibitory activity of 81.1%, also owing to the existence of flavonoids, although this aspect is effective only against Type II diabetes. It has been found that C. grandis stimulates gluconeogenesis, or inhibits glycogenolysis in diabetic rat liver. Selected research reports based on animal studies support that compounds in this plant inhibit the enzyme glucose-6-phosphatase which is one of the key liver enzymes involved in regulating glucose metabolism.
Table No. 2 In-Vivo Anti Diabetic Activity of Coccinia grandis Leaf Extracts
|
Extraction Method |
Treatment |
Animal/Induction method |
Dose |
In vivo response |
Reference |
|
|
Glucose level (mg/dl) |
% Reduction |
|||||
|
60% methanol |
10 days |
Adult Wistar strain albino rats of both sex, wt: 180-240 g, STZ: 65 mg/kg, 4 groups,6 rats |
150mg/kg |
190.00±4.6 |
36.1 |
Saikat Ghosh et al.,10 |
|
300mg/kg, |
172.83±3.7 |
41.87 |
||||
|
Glibenclamide : 0.25mg/kg |
168.00±3.6 |
43.5 |
||||
|
DC |
297.33+2.8 |
- |
||||
|
90% alcohol |
7 weeks |
8-10 weeks old albino male/ female rats, wt: 200-250 g, STZ : 60 mg/kg, 4 animals,5 group |
250mg/kg |
311.23+13.60 |
29.95 |
Ravikant et al.,11 |
|
500mg/kg |
280.12± 9.81 |
36.95 |
||||
|
Glibenclamide : 10mg/kg/day |
182.67±8.03 |
58.89 |
||||
|
DC |
444.35±12.38 |
|||||
|
Control |
113.45±1.99 |
|
||||
|
100 ml distilled water 4°C |
21 days |
Male albino rats 150-200 g, 5% Alloxan monohydrate, 6 animals,4 group |
Alloxan + leaf extract |
119.43 ± 1.61 |
37.8 |
S. Manjula et al., 12 |
|
control + leaf extract |
65.28 ± 3.28 |
- |
||||
|
DC |
192.03 ±18.07 |
- |
||||
|
1000 ml of 90% methanol |
8 hr |
Albino mice (30-35 gm), Alloxan: 150mg/kg, 3 animals,6 group |
150 mg/kg |
19.5±7.04 |
35.85 |
Md. Ataur Rahman et al.,17 |
|
300 mg/kg |
20.1±1.55 |
33.88 |
||||
|
450 mg/kg |
14.3±1.31 |
62.93 |
||||
|
Glibenclamide: 10 mg/kg |
11.27±4.64 |
62.92 |
||||
|
DC |
30.4±1.98 |
- |
||||
|
Control |
7.53±0.4 |
- |
||||
|
400 ml distilled water |
30 days |
Healthy and diabetic rats, STZ induced |
0.75 g/kg |
NA |
33% |
Jayatilaka et al.,13 |
STZ: Streptozotocin DC: Diabetic Control NA: Not Applicable
Some studies have also shown that pectin from the fruit of this plant is able to reduce the blood glucose by decreasing its absorption from the intestine and increasing liver glycogen by decreasing glycogen phosphorylase in animal models.9
Antihyperglycemic Potential of Coccinia grandis:
Reducing glucose metabolism and absorption from the gut, increasing the insulin production from the pancreas, and reducing glucose uptake by fat and muscle cells are hypothesized to be the probable mechanisms of action by which CG exerts its anti-diabetic effects.9 The in-vivo ability of various parts of CG in reducing the blood glucose levels mentioned in the Table No. 2
Significant Reduction in the elevated blood glucose level by Methanolic Leaf Extract of Coccinia grandis:
Treatment for 10 days period using 60% methanolic leaf extract of CG in order to investigate the reported anti-diabetic potential of the methanolic polyherbal extract of CG leaves in streptozotocin-induced diabetic rats were carried out by Saikat Gosh and crew. Hyperglycemia was induced by a single intraperitoneal injection of Streptozotocin made in citrate buffer. The diabetic rats in groups received treatment with two totally different concentrations of the extract, the standard drug, and saline. The effectiveness of extract in the maintenance of blood glucose level is indicated by a significant reduction of the elevated blood sugar level after 10 days of treatment up to 36.10% and 41.87% by Group II and III which is comparable to that of standard drug glibenclamide 43.50% under similar conditions. From the results, it can be witnessed that treatment with a higher concentration of methanolic extract of CG yields a greater reduction in the plasma glucose levels.10
Coccinia grandis attenuates hyperglycemia and diabetic neuropathy in STZ-induced diabetic rat:
An investigation on the effect of freshly prepared alcoholic extract of CG leaves extract on neuropathic pain, blood glucose level and loss of body weight in hyperglycaemic rats were carried out by Ravikant et al. Streptozotocin (STZ; 60mg/kg) was injected intraperitoneally to albino rats for inducing diabetes. Freshly prepared alcoholic extracts were orally administered to diabetic rats until 7 weeks after the injection of STZ at a dose of 500mg/kg/day and 250 mg/kg/day. Glibenclamide (10mg/kg/day) was used as the standard. The glucose level was tested to follow the changes in blood glucose and body weight measurement to evaluate the loss of body weight in diabetic rats. Streptozotocin-induced diabetic rats showed loss of body weight significantly at 2 weeks after the Streptozotocin treatment compared to Control rats, which further decreased at 4, 6 and 7 weeks after the Streptozotocin treatment. On the other hand treatment with freshly prepared leaf, aqueous extracts in diabetic rats showed significant prevention of body weight loss. Treatment with freshly prepared leaf alcoholic extract considerably reduced blood glucose and pain in diabetic rats.11
Coccinia grandis prevents the elevation of serum lipid levels secondary to the diabetes state:
A study aimed to investigate the hypoglycemic as well as the hypolipidemic effect of CG aqueous leaf extract in alloxan- induced diabetic rats were carried out by S. Manjula et al.,. The alloxan-induced diabetic rats treated with CG leaf extract has shown a reduction in the blood glucose of 37.8%. The authors also identified that CG leaf extract not only showed hypoglycaemic effect but also hypolipidemic effect. In alloxan- induced diabetic rats there was a significant increase in total cholesterol and triglycerides in serum compared to other groups. Continuous administration of CG leaf extract for 21 days prevented the elevation of the levels of serum lipids.12
Methanolic leaf extract of Coccinia grandis reduced blood glucose level in alloxan-induced albino mice
In order to evaluate the antidiabetic activities of methanolic extract of CG leaves, a study was carried out by Md. Ataur Rahman et al., by administering 1000ml of 90% methanolic extract of CG leaves to alloxan (150 mg/kg) induced albino mice. The leaf extracts were given in three doses of 150mg/kg, 300mg/kg and 450 mg/kg and were compared with standard drug Glibenclamide (10mg/kg). The duration of the study was 8 hrs. On administration of a single dose of leaf extract (450mg/kg b.w.) produced a significant decrease in blood glucose level (62.93%) in alloxan-induced diabetic mice after 8 hours rather than 150mg/kg b.w (300 mg/kg b.w. extract dose. On the other hand, the drug glibenclamide (10mg/kg b.w.) reduced the higher blood glucose level (11.27±4.64 mmol/L) rather than 450 mg/kg b.w extract dose. The study revealed the antidiabetic potential of methanolic extract of CG leaf extract.17
Long term effect of aqueous leaf extract of Coccinia grandis on serum glycemic parameters and regenerative potential of pancreatic islet cells of streptozotocin-induced diabetic rats:
The long term effect of aqueous leaf extract of CG on serum/blood glycemic parameters and regenerative potential of islet cells in the pancreas of streptozotocin-induced diabetic rats has been investigated by Jayatilaka et al. Diabetes was induced in rats by injecting streptozotocin (65mg/kg,ip). Group one and two served as the healthy untreated, diabetic untreated control rats and received only distilled water.
Table No. 3 In-Vivo Anti Diabetic Activity of Coccinia grandis Fruit Extracts
|
Extraction method |
Treatment |
Animal/ Induction method |
Dose |
In vivo response |
Reference |
|
|
Glucose level |
% reduction |
|||||
|
Hydroalcoholic solution (1:1) |
14 days |
Wistar Albino rats (150-180gms), alloxan: 150mg/kg, 6 rats, 6 group |
200mg/kg |
127.6 ±9.9 |
51.35 |
Manish Gunjan et al.,14 |
|
Glibenclamide: 2.5mg/kg |
118.3 ±6.2 |
54.89 |
||||
|
DC |
262.3 ± 17.7 |
- |
||||
|
Control |
90.8 ± 6.6 |
- |
||||
|
Water as solvent, 50-55°C |
21 days |
Wistar albino rats (150-200g), STZ : 50mg/kg bw,7 groups,6 animals |
100 mg/kg |
198.79 ± 16.54 |
35.49 |
V.K. Shakya,15 |
|
250 mg/kg |
172.25 ± 11.62 |
44.1 |
||||
|
500 mg/kg |
139.44 ± 7.08 |
54.75 |
||||
|
Glibenclamide: 500μg/kg |
140.99 ± 13.68 |
54.24 |
||||
|
DC |
308.16 ± 18.94 |
- |
||||
|
Control |
95.50 ± 8.75 |
- |
||||
|
2.5 litres of water, 2.5 litres 70 % ethanol, 2.5 litres 60 % chloroform, 65°C |
7 hr |
Adult wistar albino rats, wt:180-240gm, alloxan: 150mg/kg bw, (2 ml), 6 rats, 6 group |
250mg/kg chloroform extract |
191.7 ±4.009 |
13.64 |
M. Ramakrishnan et al.,16 |
|
250mg/kg ethanol extract |
184.8 ±3.818 |
16.75 |
||||
|
250mg/kg aqueous extract |
195.0 ±2.897 |
12.16 |
||||
|
Glibenclamide: 1mg/kg |
146.67 ±6.48 |
33.93 |
||||
|
DC |
222.0 ±4.058 |
- |
||||
|
Control |
99.74 ±1.133 |
- |
||||
|
1000 ml 90% methanol |
8 hr |
Albino mice (30-35 gm), Alloxan: 150mg/kg, 3 animals, 6 group |
150 mg/kg |
17.9±12.18 |
41.11 |
Jyotirmoy Sarker et al.,17 |
|
300 mg/kg |
19.6±11.6 |
35.52 |
||||
|
450 mg/kg |
9.4±0.46 |
69.07 |
||||
|
Glibenclamide : 10mg/kg |
11.27±4.64 |
62.92 |
||||
|
DC |
30.4±1.98 |
- |
||||
|
Control |
7.53±0.4 |
- |
||||
STZ : Streptozotocin DC : Diabetic Control
Group three and four were diabetic rats, received the optimum effective dose of CG (0.75gm/kg) and glibenclamide (0.50mg/kg) daily for 30 days. A statistically significant decrease in the percentage of glycosylated hemoglobin with a concomitant increase in the concentrations of serum insulin and C-peptide in plant extract and glibenclamide treated diabetic rats was observed. The β-cell regeneration in CG extract treated diabetic rats was noted through an increase in the percentage of insulin secreting β-cells and an increase in islet profile diameter.13
Blood glucose lowering potential of the Hydroalcoholic fruit extract of Coccinia grandis:
Hydroalcoholic fruit extract of CG administered to alloxan induced diabetic rats for 14 days in order to evaluate its antihyperglycemic potential was carried out by Manish Gunjan et al. Chronic administration of kundru fruit extracts (200mg/kg) for 14 days reduced the blood glucose level up to 51% in diabetes-induced animals as compared to the diabetic control group. There was a significant decrease in the blood glucose level following the 7th and 14th days of diabetes induction, showing the antidiabetic effect of the concerned fruit. The effect was comparable to that of standard antidiabetic drug Glibenclamide that produced a blood glucose reduction of 54%.14
Coccinia grandis aqueous fruit extract can reduce the blood sugar and cholesterol levels in streptozotocin-induced rats:
A study exclusively aimed to investigate the therapeutic effect of CG fruits extract in streptozotocin- induced diabetic rats was conducted by V.K Shakya. Albino rats were used for the experimental bioassay. Animals were made diabetic by single intraperitoneal injection of STZ at 50mg/kg body weight. Animals were randomly divided into seven groups with six animals in each. Upon single oral administration daily for three weeks of aqueous extract at doses of 100, 250 and 500mg/kg b.w significantly lowered the blood glucose and cholesterol levels lowered in diabetic rats. Glibenclamide was used as the reference drug which showed a similar result at the dose of 500µg/ kg as that of 500 mg/kg of extract.15
Hypoglycemic activity of ethanolic extract of Coccinia grandis:
Chloroform, ethanolic and aqueous fruit extracts of CG were evaluated for their antidiabetic activity in alloxan-induced diabetic rats by M. Ramakrishnan et al. Diabetes was induced in experimental rats by a single intraperitoneal injection of alloxan monohydrate (150 mg/kg body weight). All the extracts were provided at the same dose of 250mg/kg. Glibenclamide 1mg/kg bw was used as the standard. Of the three extracts, the ethanolic extract produced the maximum reduction and the standard has produced a reduction of 33%.16
Methanolic fruit extract of Coccinia grandis could reduce blood glucose level near to Control:
The administration of a single dose of fruit extract (450 mg/kg bw) reduced blood glucose level to about 69 % after 8 hours just near to normal mice which is comparatively higher than other doses 150 mg/kg (41%) and 300 mg/kg (35%). Glibenclamide 10mg/kg is used as the standard which was able to reduce the glucose level to 62%. 17
RESULTS AND DISCUSSION:
Diabetes mellitus of long duration is associated with several complications such as atherosclerosis, myocardial infarction, nephropathy, etc. These complications are usually related to chronically elevated blood glucose level. A number of plants were found to possess hypoglycemic effects and the possible mechanism suggested for such hypoglycemic actions could be through the increased insulin secretion from islets of Langerhans of β-cells or its release from the bound insulin. Administration of the numerous extracts of CG in different diabetic animal models has resulted in a decrease in the blood glucose levels.17 The antidiabetic effects of different parts of CG with respect to Standard drug at different concentration are discussed in fig 1
The figure (Figure-1) above represents the comparison of % glucose reduction of various extracts of CG leaf with Standard drug Glibenclamide at different doses. In the figure points, A to H represents the different doses of leaf extracts taken for various studies discussed in the tables and I to K represents doses of Glibenclamide to be compared. In the graph point G that signifies methanolic extract of CG leaf 450 mg/kg and point K corresponds to Glibenclamide 10mg/kg shows a peak glucose reduction with similar values.
The next higher reduction is again indicated by Standard. 450mg/kg of methanolic extract of CG leaf was able to produce the same % glucose reduction as that of the Standard. Thus CG represents a similar reduction potential to Glibenclamide 10mg/kg. Glibenclamide 10mg/kg was represented twice in the graph which is taken from 2 different studies.
The figure (2) contains 14 different points from A to N characterized by the % glucose reduction of various extracts of CG fruit with respect to Standard. Points A to J represents the various extracts of CG administered at different doses to animals following the studies and K to N points stands for doses of Glibenclamide tried. It is absolutely clear from the graph that point J (aqueous fruit extract 450mg/kg) could reduce blood glucose to its maximum of 69% compared to other extracts and the next highest reduction is exhibited by point N (Glibenclamide 10mg/kg). So the fruit extract of CG was able to lower the blood glucose level far better than the highest dose of Standard. Points K and L that is 2.5 mg/kg and 500µg/kg of Glibenclamide exhibited the same reduction potential 54%.
The best among leaf extract was found to be Methanolic leaf extract 450mg/kg and among the fruit extract was found to be aqueous fruit extract 450mg/kg and the overall blood glucose reduction follows the order: Fruit extract of CG> Leaf extract.
CONCLUSION:
Medicinal plants are considered to be potent candidates for new drug discovery. These medicinal plants provide a rich mine for bioactive constituents that are free from side effects and have powerful pharmacological actions. Even though multiple therapies are available for the treatment of diabetes herbal therapy for diabetes has been followed all over the world successfully. The results of the present study disclosed the effective glycaemic control of CG and its therapeutic usefulness. The presence of alkaloids, tannins, saponins, terpenoids, flavonoids, phenolics and glycosides as the possible biologically active principles have found to possess hypoglycemic as well as antihyperglycemic activity. Therefore much effort should be afforded to optimize a procedure for antidiabetic screening of the plant extracts as well as isolated bioactive compounds for the discovery of new herbal antidiabetic drugs that can be used as alternatives to synthetic oral hypoglycemic drugs with less or perhaps no prominent side effects.
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Received on 21.06.2019 Modified on 29.06.2019
Accepted on 01.11.2019 © RJPT All right reserved
Research J. Pharm. and Tech. 2020; 13(4):1949-1954.
DOI: 10.5958/0974-360X.2020.00351.0