ANTIDIABETIC POTENTIAL OF IVY GOURD (COCCINIA GRANDIS, FAMILY: CUCURBITACEAE) GROWN IN SRI LANKA: A REVIEWHTML Full Text
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 7th 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 HbA1C 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 30th 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 126.96.36.199), glutathione peroxidize (EC 188.8.131.52), glutathione S-transferase (EC 184.108.40.206), 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
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.
CONFLICT OF INTEREST: Nil
- Zimmet PZ, Magliano DJ, Herman WH and Shaw JE: Diabetes: A 21st-century challenge. Lancet Diabetes Endocrinology 2014; 2(1): 56-64.
- Bhattacharya M: A historical exploration of Indian diets and a possible link to insulin resistance syndrome. Appetite 2015; 95: 421-454.
- Cho SS, Qi L, Fahey GCr and Klurfeld DM: Consumption of cereal fiber, mixtures of whole grains and bran, and whole grains and risk reduction in type 2 diabetes, obesity, and cardiovascular disease. American Journal of Clinical Nutrition 2013. http://dx.doi: 10.3945/ajcn.113.067629.
- Post RE, Mainous AG, King DE and Simpson KN: Dietary fiber for the treatment of type 2 diabetes mellitus: A meta-analysis. Journal of American Board of Family Medicine 2012; 25 (1): 16-23.
- Ley SH, Hamdy O, Mohan V and Hu FB: Prevention and management of type 2 diabetes: Dietary components and nutritional strategies. The Lancet 2014; 383(9933): 1999-2007.
- Ediriweera ERHSS and Ratnasooriya WD: A review on herbs used in the treatment of diabetes mellitus by Sri Lankan Ayurvedic and Traditional Physicians. Ayu 2009; 30: 373-391.
- Medagama AB, Bandara R, Abeysekera RA, Imbulpitiya B and Pushpakumari T: Use of complementary and alternative medicines (CAMs) among type 2 diabetes patients in Sri Lanka: A cross-sectional survey. BMC Complementary and Alternative Medicine 2014. http://doi.10.1186/ 1472 -6882-14-374.
- Jayaweera DMA: Medicinal Plants (indigenous and exotic) used in Ceylon. 2nd Sri Lanka, Colombo 1982.
- Forbes JM, Cooper ME: Mechanisms of diabetic complications. Physiological Reviews 2011; 93(1): 137-188.
- ADA (American Diabetes Association). Clinical practice recommendations Diabetes Care 2016; 20(30): S16.
- Attanayake AP, Jayatilaka KAPW, Pathirana C and Mudduwa LKB: Study of antihyperglycaemic activity of some Sri Lankan medicinal plants in alloxan-induced diabetic rats. Ancient Science of life 2013; 32(4): 193-8.
- Attanayake AP, Jayatilaka KAPW, Pathirana C and Mudduwa LKB: Acute hypoglycemic and antihyperglycemic effects of ten Sri Lankan medicinal plant extracts in healthy and streptozotocin-induced diabetic rats. International Journal of Diabetes in Developing Countries 2014. doi.10.1007/s13410-014-0217-8.
- Munasinghe MAAK. Abeysena C, Yaddehige IS, Vidanapathirana T and Piyumal KPB: Blood sugar lowering effect of Coccinia grandis (L.) J. Voigt: Path for a new drug for diabetes mellitus. Experimental Diabetes Research 2011. http://dx.doi.org/10.1155/2011/978762.
- Ndong M, Uehara M, Katsumata S and Suzuki K: Effects of oral administration of Moringaoleifera Lam on glucose tolerance in Goto-Kakizaki and Wistar Rats. Journal of Clinical Biochemistry and Nutrition 2007; 40(3): 229-233.
- Attanayake AP, Jayatilaka KAPW, Pathirana C and Mudduwa LKB: Antihyperglycemic activity of Coccinia grandis (L.) Voigt (Cucurbitaceae) in streptozotocin-induced diabetic rats. Indian Journal of Traditional Knowledge 2015; 14(3): 376-381.
- Pekamwar SS, Kalyankar TM and Kokate SS: Pharmacological Activities of Coccinia grandis: Review. Journal of Applied Pharmaceutical Science 2013; 3(05): 114-119.
- Deokate UA and Khadabadi SS: Pharmacology and phytochemistry of Coccinia indica Pharmacophore 2012; 3(3): 179-185.
- Balaraman AK, Singh J, Dash S and Maity TK: Antihyperglycemic and hypolipidemic effects of Melothria maderaspatana and Coccinia indica in streptozotocin-induced diabetes in rats. Saudi Pharmaceutical Journal 2010; 18(3): 173-178.
- Ashcroft FM and Rorsman P: Diabetes mellitus and the beta cell: the last ten years. Cell 2012; 148: 1160-1171.
- Ferrannini E: The stunned beta cell: a brief history. Cell Metabolism 2010; 11: 349-352.
- Hosseini A, Shafiee-Nick R and Ghorbani A: Pancreatic beta cell protection/regeneration with phytotherapy. Brazilian. Journal of Pharmaceutical. Sciences 2015; 51: 1-16.
- Vetere A, Choudhary A, Burns SM and Wagner BK: Targeting the pancreatic β-cell to treat diabetes. Nature Reviews Drug Discovery 2014; 14: 278 -289.
- Tangvarasittichai S: Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World Journal of Diabetes 2015; 6(3): 456-480.
- Farzaei MH, Rahimi R, Farzaei F and Abdollahi M: Traditional medicinal herbs for the management of diabetes and its complications: An evidence-based review. International Journal of Pharmacology 2015; 11: 874-887.
- Mohammed SI, Chopda MZ, Patil RH , Vishwakarma KS and Maheshwari VL: In-vivo antidiabetic and antioxidant activities of Coccinia grandis leaf extract against streptozotocin-induced diabetes in experimental rats Asian Pacific Journal of Tropical Disease 2016; 6(4): 298-304.
- Krishnakumari S, Bhuvaneswari P and Rajeswari P: Ameliorative potential of Coccinia grandis extract on serum and liver marker enzymes and lipid profile in streptozotocin-induced diabetic rats. Anc Sci Life 2011; 31(1): 26-30.
- ManjulaS and Ragavan B: Hypoglycemic and hypolipidemic effect of Coccinia indica Wight and Arn in alloxan-induced diabetic rats. Ancient Science of Life 2007; 27(2): 34-37.
- Tiwari BK, Pandey KB, Abidi AB, Rizvi SI: Markers of oxidative stress during diabetes mellitus. Journal of Biomarkers 2014. http://dx.doi.org/10.1155/2013/378790.
- Kurutas EB: The importance of antioxidants which play a role in cellular response against oxidative/nitrosative stress. Nutrition Journal 2015. doi: http://10.1186/s 12937 -016-0186-5.
- Attanayake AP, Jayatilaka KAPW, Mudduwa LKB and Pathirana C: In vivo antihyperlipidemic, antioxidative effects of Coccinia grandis (L.) Voigt (Cucurbitaceae) leaf extract: An approach to scrutinize the therapeutic benefits of traditional Sri Lankan medicines against diabetic complications. International Journal of Pharmaceutical Sciences and Research 2016; 7(10): 3949-3958.
- Perera HKI and Handuwalage CS: Analysis of glycation induced protein cross-linking inhibitory effects of some antidiabetic plants and spices. BMC Complementary and Alternative Medicine 2015. http://doi.10.1186/s12906-015-0689-1.7.
- Attanayake AP, Jayatilaka KAPW, Pathirana C and Mudduwa LKB: Phytochemical screening and in-vitro antioxidant potentials of extracts of ten medicinal plants used for the treatment of diabetes mellitus in Sri Lanka. African Journal of Traditional Complementary and Alternative Medicines 2015b; 12(4): 28-33.
- Kunle OF, Egharevba HO and Ahmadu PO: Standardization of herbal medicines - A review International Journal of Biodiversity and Conservation. 2012; 4(3): 101-112.
- Attanayake AP, Arawwawala LDAM and Jayatilaka KAPW: Chemical standardization of leaf extract of Coccinia grandis (L.) Voigt (Cucurbitaceae) of Sri Lankan origin, Journal of Pharmacognosy and Phytochemistry 2016; 5(5): 119-123.
- Ekor E: The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Frontiers in Pharmacology 2013. http://doi: 10.3389/fphar.2013.00177.
- Jordan SA, Cunningham DG and Marles RJ: Assessment of herbal medicinal products: Challenges and opportunities to increase the knowledge base for safety assessment. Toxicology and Applied Pharmacol 2010; 243(2): 198-16.
- Attanayake AP, Jayatilaka KAPW, Pathirana C and Mudduwa LKB: Efficacy and toxicological evaluation of Coccinia grandis (Cucurbitaceae) extract in male Wistar rats. Asian Pacific Journal of Tropical Disease 2013(b); 3(6): 460-466.
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.
This Journal licensed under a Creative Commons Attribution-Non-commercial-Share Alike 3.0 Unported License.
A. P. Attanayake * , K. A. P. W. Jayatilaka and L. K. B. Mudduwa
Department of Biochemistry, Faculty of Medicine, University of Ruhuna, Sri Lanka.
03 December 2016
18 January 2017
22 February 2017
01 March 2017