ANTIDIABETIC POTENTIAL OF IVY GOURD (COCCINIA GRANDIS, FAMILY: CUCURBITACEAE) GROWN IN SRI LANKA: A REVIEW

ANTIDIABETIC POTENTIAL OF IVY GOURD (COCCINIA GRANDIS, FAMILY: CUCURBITACEAE) GROWN IN SRI LANKA: A REVIEW

A. P. Attanayake ^{* 1}, K. A. P. W. Jayatilaka ¹ and L. K. B. Mudduwa ²

Department of Biochemistry ¹, Department of Pathology ², Faculty of Medicine, University of Ruhuna, Sri Lanka.

ABSTRACT: Leaves of ivy gourd; Coccinia grandis (L.) Voigt (Family: Cucurbitaceae) is one of the well-known leafy vegetables, which has been consumed by Sri Lankans for centuries. The therapeutic potential of ivy gourd against diabetes is brought mainly by its antihyperglycemic, β-cell regenerative, antihyperlipidemic and antioxidant properties. Also, the optimum effective therapeutic dose of the aqueous C. grandis extract was found to be safe in terms of hepatotoxicity, renotoxicity, hematotoxicity in-vivo. The scientific investigations confirmed the effectiveness of this leafy vegetable for the development of potential neutraceuticals against diabetes mellitus.

Antidibetic potential, Coccinia grandis, Standardization, Toxicity studies

INTRODUCTION: Diabetes mellitus has become a major global epidemic over the past few decades. The prevalence of diabetes has been increased worldwide and has reached alarming levels in many countries around the world. It is estimated that 415 million people (6.4% of the adult population worldwide) were affected by diabetes in 2015, and the number is projected to increase to 642 million in 2040. Accordingly, it is predicted to become the 7^th leading cause of death in the world by the year 2040 ¹. In the past couple of decades, evidence from prospective observational studies and clinical trials has converged to support the importance of individual nutrients, foods, and dietary patterns in the prevention and management of diabetes mellitus.

Medicinal plants have long been used as medications or/and as simple dietary adjuncts to the existing therapies since antiquity. Before the introduction of insulin in 1922, the treatments for diabetes mellitus relied mainly on the recommendations of herbal preparations of edible medicinal plants ². However, from the past to the present, the dietary recommendations for diabetes have widened, with the appreciation that fiber-rich food such as leafy vegetables would be able to enhance the glycemic control of patients with diabetes and thereby prevent the progression of the disease into diabetic complications ^{3, 4, 5}. However, in this sense, the investigation of antidiabetic activity of edible, medicinal plants is imperative, as with proven in-vivo efficacy. These would be recommended as dietary adjuncts to the conventional therapies and more importantly can attribute for the development of potential sources of neutraceuticals.

A multitude of herbs, spices, and other plant materials have been described in the management of diabetes mellitus in Sri Lanka ⁶.

However, several edible, medicinal plants have been attributed to a special value in the diet of Sri Lankans. Ivy gourd; Coccinia grandis (L.) Voigt (Family: Cucurbitaceae) is one of the well-known leafy vegetables, which has been consumed by Sri Lankans for centuries. It is also known as a scarlet gourd in English; Kowakka, Kobowakka, Kem-well in Sinhala; Kovai, Kwai in Tamil. The plant is widely distributed in Southern, Western and North Central regions in the country. It is a perennial climber with single tendrils and glabrous leaves. Generally, the leaves have five lobes and are 6.5–8.5 cm long and 7–8 cm wide ⁷. Even though the reputed effects of leaf extract of C. grandis have not been evaluated critically, it is widely used for the glycemic control by the local population. Accordingly, the results of a cross-sectional survey using an interviewer based questionnaire clearly showed that the leaves of C. grandis had been commonly used as a complementary and alternative medicine by patients with diabetes mellitus in Sri Lanka ⁷.

Several scientific reviews are published on pharmacological properties of C. grandis grown in different geographical locations in the world; however, to date a comprehensive report on the antidiabetic potential of C. grandis of Sri Lankan origin has not been published. The present review aims to provide a comprehensive summary of the investigations carried out on the antidiabetic and toxicological effects of the leaves of Ivy gourd grown in Sri Lanka to corroborate its proposed antidiabetic potential in patients with diabetes mellitus.

Antihyperglycemic Activity: Hyperglycemia is the fundamental biochemical derangement in diabetes mellitus, causing oxidative and nitrosative stress, activation of inflammatory pathways and endothelial dysfunction, leading to vascular complications ^{8, 9, 10}. However, effective blood glucose control is primarily targeted in the management of diabetes mellitus.  Investigations carried out by Attanayake and coworkers ^{11, 12} demonstrated that the leaf extract of C. grandis of Sri Lankan origin exerted both acute and long term antihyperglycemic effects in healthy, alloxan induced and streptozotocin-induced diabetic rats. The optimum therapeutic dose of the aqueous leaf extract of C. grandis upon a glucose load was 0.75g/kg in healthy and diabetic rats. Leaf extract of C. grandis at the optimum effective dose lowered the blood glucose concentration gradually during four hours in diabetic rats. The highest reduction (33%) in the blood glucose concentration was observed in the second hour after the administration of C. grandis extracts in streptozotocin-induced diabetic rats. Also, Munasinghe and co-workers ¹³ reported a phase 1 clinical trial of an ingestion of a meal containing 20 g of leaves of C. grandis mixed with a measured amount of scraped coconut and table salt were able to show acute hypoglycemic effects in a selected group of healthy subjects.

The acute antihyperglycemic activity of C. Grandis may is due to a reduction in the absorption of glucose in the small intestine, stimulation of glucose-induced secretion of insulin from the pancreatic β-cells, enhancement of uptake of glucose by peripheral tissues, etc. ¹⁴ The long term antihyperglycemic activity is also evident in C. grandis treated diabetic rats. The diabetic rats treated with the optimum therapeutic dose of the aqueous extract of C. grandis exhibited a remarkable glycemic control as evident by a reduction in the percentage of HbA_1C in streptozotocin-induced diabetic rats ¹⁵. Accordingly, the concentration of fasting serum fructosamine, insulin and C-peptide were decreased significantly in diabetic rats. The results reported by Attanayake et al., ¹⁵ corroborate with the findings on antihyperglycemic efficacy of C. grandis grown in India ^{16, 17, 18}.

β-cell Regenerative Potency: The optimum pancreatic β-cell function is essential for the regulation of intracellular glucose homeostasis. Several studies have provided evidence that loss of functional β-cell mass through apoptosis and impaired proliferation consequent to hyperglycemia is considered as a hallmark of diabetes mellitus ¹⁹. Regulation of functional β-cell mass has been considered as a critical therapeutic challenge in patients with the disease ²⁰. However, islet cell regeneration has gained much interest and has been considered as a strategy to restore the loss of β-cell mass in diabetes mellitus. Stimulation of β-cell proliferation/regeneration may have an impact on the insulin-producing cells in the pancreas ²¹. One such approach to foster restoration and regeneration of β-cells is from putative exogenous sources as edible medicinal plants ²². Accordingly, the extract of C. grandis of Sri Lankan origin showed β-cell regeneration as evident through an increase in the number of insulin secreting β-cells in streptozotocin-induced diabetic rats. An increase in the diameter of small, medium and large islets was found in C. grandis treated diabetic rats, and it was confirmed that the functional mass of the islet and the entire regenerative capacity of the pancreas increased with the treatment of C. grandis extract in diabetic rats ¹⁵. In contrast, none of the species of C. grandis except the variety found in Sri Lanka reported the β cell regenerative potency in vivo to date.

Antihyperlipidemic Activity: Lipid abnormalities are postulated to be major causes of complications associated with diabetes mellitus. Indeed, dyslipidemia in diabetes mellitus is generally comprised of low levels of high-density lipoprotein cholesterol (HDL-C), high levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) ²³. Several studies have revealed that a positive correlation between dyslipidemia and development of premature atherosclerosis, coronary insufficiency and myocardial infarction in diabetic subjects ^{9, 22}. Thus, the effect of natural products in the management of diabetic complications has recently received considerable attention, highlighting the importance of edible leafy vegetables as regulators of metabolism of carbohydrate and lipids ²⁴.

Recent studies by Attanayake and coworkers have demonstrated that a significant reduction in the concentration of serum TC, TG, LDL-C and an elevation in the concentration of HDL-C in streptozotocin-induced diabetic rats on the 30^th day of study ¹⁵. This is similarly mentioned by other authors who observed potential antihyperlipidemic effects in serum lipid parameters in diabetic rats with the leaf extract of C. grandis of Indian origin ^{25, 26}. The favorable effects of aqueous leaf extract of C. grandis on serum lipid parameters in addition to the glycemic control would be useful in the development of neutraceuticals targeting diverse disease pathologies of diabetes mellitus. The increase in the concentration of HDL-C by C. grandis is of the therapeutic advantage as it improves the glycemic control as well as reduces the cardiovascular risk associated with diabetes mellitus. The strong antihyperlipidemic effect by the administration of C. grandis in diabetic rats could be through its control on hyperglycemia or/and direct actions on the absorption of intestinal cholesterol and biosynthesis of cholesterol as suggested by many authors ^{26, 27}.

Antioxidant Activity: Oxidative stress is one of the major factors underlying the resistance for insulin in disease pathogenesis of diabetes mellitus ²⁸. Elevated free fatty acids, glycation of proteins, other circulating factors, leptin and the simultaneous decline of cellular antioxidant defense mechanisms in patients with diabetes contribute to causing an overproduction of reactive oxygen species ⁹.

Edible, medicinal plant extracts with strong antioxidative properties have been the recent focus in diminishing cellular oxidative stress in diabetes mellitus. The increase in reactive oxygen species may lead to disruption of cellular functions, oxidative damage to membranes and lipid peroxidation that consequently lead to the occurrence of diabetic complications.  Also, it has been shown that dietary supplementation with natural antioxidants such as Vitamins C and E, melatonin, and flavonoids attenuates the oxidative stress in diabetic subjects ²⁹.

The overall experimental data reported by Attanayake et al., ³⁰ indicated that the administration of leaf extract of C.  grandis was able to improve the activities of antioxidant enzymes such as glutathione reductase (EC 1.6.4.2), glutathione peroxidize (EC 1.11.1.9), glutathione S-transferase (EC 2.5.1.18), increase the concentration of reduced glutathione  and decrease the concentration of malonaldehyde as a product in the lipid peroxidation in diabetic rats.

Also, the in-vitro glycation induced protein cross-linking inhibitory effects of the leaf extract of C. grandis was also proven ³¹. The in-vivo antioxidant activity is further corroborated by the relatively high in-vitro antioxidant activity of C. grandis compared determined using three in-vitro assays of 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH) radical scavenging activity, ferric reducing power (FRAP) and nitric oxide (NO) inhibition ³².

The in-vivo antioxidative activity of C. grandis may be due to the presence of a wide range of phytochemicals principally due to the high content of polyphenolic and flavonoid compounds as suggested by Attanayake et al. ³²

Safety Profile:

Chemical Standardization: Standardization of crude plant extracts involves the process of prescribing a set of standards or inherited characteristics, constant parameters, definitive quality and quantitative values that carry an assurance of quality, safety and reproducibility ³³. The C. grandis grown in Sri Lanka has a very low amount of acid insoluble ash content, and a moderate level of total ash content indicates the purity of the leaves of C. grandis leaves that could be useful in human consumption and development of neutraceutical products. According to the recent report by Attanayake et al., ³⁴ heavy metals were not detected in C. grandis leaves of Sri Lankan origin.

In-vivo Toxicity Studies: The use of edible, medicinal plants for therapeutic purposes has been increasingly popular as they are believed as beneficial and free of side effects ^{35, 36}. However, the rationale for the utilization of plant food has rested largely on long-term clinical experience with little or no scientific data on safety. Attanayake and coworkers reported that the administration of C. grandis at a range of doses (0.25 g/kg-2.00 g/kg) in healthy Wistar was well tolerated by test animals, suggesting it’s in-vivo safety. Further, the long term administration of the extract to Wistar rats for 28 days was not associated with adverse effects reflected in the general condition, growth, relative weight of organs, clinical biochemical, hematological values and more importantly did not cause abnormalities in the histopathology of body tissues ³⁷. However, a proper clinical evaluation may be required to define a safe dosage in humans precisely.

CONCLUSION: This is the first scientific review that describes the potential antidiabetic activities and toxicological effects of C. grandis grown in Sri Lanka. The fact that the aqueous leaf extract of C. Grandis exerts antihyperglycemic, antihyper-lipidemic, antioxidant activities in-vivo merits its use in the development of potential neutraceuticals against diabetes mellitus. However, there is an urgent need for the determination of its clinical efficacy on diabetic subjects through well-defined and adequately powered randomized controlled clinical trials before the recommendation of ivy gourd as an effective dietary supplement for patients with diabetes mellitus.

ACKNOWLEDGEMENT: Nil

CONFLICT OF INTEREST: Nil

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    How to cite this article:

    Attanayake AP, Jayatilaka KAPW and Mudduwa LKB: Antidiabetic potential of ivy gourd (Coccinia grandis, Family: Cucurbitaceae) grown in Sri lanka: a review. Int J Pharmacognosy 2017; 4(3): 79-83. doi link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.4(3).79-83.

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