INTRODUCTION:

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by disturbances in the Carbohydrate, protein and lipid metabolism leading to microvascular and macrovascular complications. Metabolic regulation of glucose is an interplay between two hormones, namely insulin and glucagon, which is secreted from the β and α cells of pancreas respectively. When this regulation gets disrupted due to genetic factors or environmental factors, like sedentary lifestyle, DM results.¹But in the present situation, the chronic use of the oral hypoglycemic agents also cannot bring a constant control on hyperglycemia rather than it brings upon increased incidence of adverse effects.² The situation calls for some other alternative that could be more safer economically acceptable.

Researchers tirelessly work on herbal plants to come up as a suitable surrogate to synthetic agents. Though the efficacy of natural products did not come so close to that of synthetic agents in terms of its onset and duration of action, the safety aspects, economic feasibility encourages patient welfare and agricultural enrichment. Moreover, the herbal plants possess auxiliary therapeutic benefits, in contrast to the adverse effects of synthetic ones, it promotes a holistic approach in treatment and maintains a constant therapeutic effect rather than any withdrawal effects. Isolation of active moieties from the plants and its further development to formulation still favors the better therapeutic outcome and they can also act as lead molecules for the evolution of drugs with more efficacy and least adverse effects.The present work aims to identify the various pharmacological properties of Cocos nucifera and to reveal its potentiality as an antihyperglycemic agent, parts possessing antidiabetic activity, explore the various studies conducted on this specific plant.

METHODOLOGY:

Selected both research and review articles published in peer review journals, on the various activities of different plant parts of the coconut palm. Sources include Google Scholar, Pubmed, Science direct. Initially, the papers were categorized based on the response produced via in-vivo or in-vitro for the different parts and later they were compared to identify the potential part of the palm.

Cocos nucifera (Coconut palm):

Cocos nucifera also called coconut tree or coconut Palm belongs to Arecaceae family (Palm family) is widely distributed in the world and India occupies a predominant position in the production of coconut. Both tall and dwarf varieties, as well as intermediate hybrid both natural and genetically modified, can be seen. Every part of the coconut Palm like fruit, kernel, tender coconut water, coir has nutritional, medicinal and Commercial Importance.³Besides carbohydrates, proteins, fats, fiber the phytochemical analysis revealed the presence of flavonoids, alkaloids, resins, phenolics with different properties. Screening of various pharmacological activities have been conducted with different plant parts and it was found that coconut palm has wonderful therapeutic potentials being anti-inflammatory, antibacterial, antioxidant, antidiabetic, cardioprotective, antithrombotic, antiatherosclerotic, hypolipidemic.⁴

Table 1: Taxonomical Classification of Cocos nucifera⁵

Taxonomical Classification of Cocos nucifera
Kingdom	Plantae
Subkingdom	Tracheobionta
Superdivision	Spermatophyta
Division	Mangnoliophyta
Class	Liliopsida
Subclass	Arecida
Order	Arecales
Family	Arecaceae
Genus	Cocos
Species	nucifera

Traditional Health Benefits of Cocos nucifera:

The different parts of Cocos nucifera possess multifaceted health benefits and hence used in different parts of the world for various ailments, for a time much before explored by the scientists. They include, antimicrobial and antifungal treatment for skin diseases like ringworms, psoriasis candidiasis, sore throat, sores, skin burns, sunburns, toothache, and ulcer.^6,7Coconut oil has anti-aging property and hence used as oil massage to remove heel cracks and removing darkening of armpits. To treat scalp and hair problems such as dandruff to baldness and greying of hairs. As an antidote for pesticide poisoning. As diuretics and used for the treatment of renal problems.⁶

Scientific Health Benefits of Cocos nucifera:

Coconut promotes protection to our body through the immune system. Coconut water containing amino acids not only contributes to energy buildup but produces lymphocytes that help to boost up the immune function. It improves the digestion and absorption of nutrients.⁶ Antimicrobial activity possessed by the lipid constituents such as caprylic acid, lauric acid. The plant helps strengthen the immune system by converting lauric acid into monolaurin which limits the activities of the virus. Coconut also fights against bacteria such as Listeria monocytogenes & Heliobacter pylori that cause throat infections, ulcers, pneumonia, gonorrhea, and urinary tract infections. The medium-chain fatty acids found in coconut oil increases the High Density Lipoprotein (HDL) level while lowering the Low Density Lipoprotein (LDL) in the blood thus improving HDL to LDL ratio which lowers the risks for heart diseases. The cytokinins present in coconut water also have a cardioprotectiverole.The p-Coumaric acid, a constituent seen in coconut oil halts the formation of arterial plaque by reducing the stickiness of the blood platelet thus lessens the risk of damaging the arteries and preventing the development of atherosclerosis and lowering the blood pressure. Virgin coconut oil contains potent antioxidants such as Tocopherol, p-Coumaric acids and Ferulic acid which can quench the free radicals produced in our body and therefore have a role in the treatment of free radical-mediated diseased conditions including cancer.^6,9,10Metabolism of oral bacteria can be prevented by mannitol in coconut water, it also prevents the increase in the acidity of mouth after ingestion, and can be utilized as an anticaries agent in dentistry. Organic acids such as malic and citric acid present in tender coconut water, inhibit the growth of microorganisms such as yeast moulds and bacteria. Coconut water is an indispensable source of calcium which could balance the calcium levels in the body thereby preventing nutritional rickets.^6,8

Antidiabetic property of Cocos nucifera:

The antidiabetic effect of different plant parts of Cocos nucifera has been studied both in-vivo and in-vitro. The in-vitro study includes the inhibitory potential of different extracts of Cocos nucifera against alpha-amylase and alpha-glucosidase, the enzymes responsible for the breakdown of carbohydrates to glucose. The in-vivo studies depict the antihyperglycemic action of extracts in either STZ or alloxan-induced diabetic animals. These diabetogenic agents act by destructing the beta cells of the pancreas causing the deficiency of insulin.¹¹

Inflorescence extract- potentiates insulin action:

Combination of inflorescence extract with metformin reduces the blood glucose level significantly which indicates that the combination can help to lower the dose of the synthetic drug without compromising the antidiabetic effect. The extracts work by repairing and rejuvenating beta cell, inhibition of Alpha glucosidase enzyme and reducing the oxidative stress and it also increases glycolysis at the peripheral tissues by potentiating the insulin action similar to metformin. The phytochemical screening of ethanolic and methanolic extract shows the presence of carbohydrates, phenolic compounds, alkaloids, tannins, resins, and flavonoids. Hypoglycemic activity is attributed due to the bioflavonoids.¹¹

Coconut kernel –Reduces absorption of glucose:

In-vitro studies revealed the reduction in absorption of a number of organic and inorganic substances from the gastrointestinal tract itself though it depends on the source of fiber and nutrients in question. The hypoglycemic effect of neutral detergent fiber extracted from coconut kernel reduces the absorption of glucose in two ways:

1 Binding of glucose to fiber which makes less glucose available for absorption

2 Decreased transit time caused by fiber which results in less time available for absorption

The glucose binds to various products formed as a result of digestion by microflora like hemicellulose monosaccharides, oligosaccharides. The binding involves the hydroxyl and carboxylic group of uronic acid of hemicelluloses.¹²

Coconut water-Stimulates beta cells:

The lyophilized form of mature coconut water is able to produce an antihyperglycemic effect possibly by stimulating Beta cells of the pancreas to secrete insulin which enhances glycolysis. It could able to reduce the markers of renal dysfunction like creatinine, urea and normalized liver markers like serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and serum protein content in alloxan-induced diabetic rats. It is suggested that L- Arginine is responsible for the beneficial effect in Diabetes.¹³ Similar effects were found with ethanolic extract of flowers in streptozotocin-induced diabetic rats.¹⁴

Young inflorescence- Antihyperglycemic, Cytoprotective:

R.S Renjith et al demonstrated the cytoprotective, antihyperglycemic effect of the young inflorescence of Cocos nucifera methanolic extract in streptozotocin-induced diabetic rats. The phytochemical analysis which showed the presence of polyphenols flavonoids dietary fibers and amino acids like arginine, leucine is contributing to the antihyperglycemic effect.¹⁵The ethanolic extract of endocarp exerts antihyperglycemic effect possibly due to the potentiation of pancreatic secretion of insulin and by the peripheral uptake of glucose.¹⁶

Tender Coconut Water- Produce Hypoglycemic effect:

Swayamjeet Satapathy studied the hypoglycemic potential of tender coconut water in euglycemic human subject by OGTT test and it was found that the soluble fibers and some other constituent of tender coconut water suppress the increased blood glucose level from 60 minutes onwards by reducing the intestinal absorption and promoting easy uptake in to cells thereby facilitates early clearance of glucose from blood.¹⁷Green Coconut has much water and is rich in carbohydrates, proteins, minerals, vitamins, inorganic ions like calcium, Phosphorus, iron, iodine, chlorine, sulfur, potassium, and magnesium. The water assists in the hydration of the body. Sucrose, sorbitol, glucose, and fructose are the main sugars in mature coconut water followed by minor sugars including galactose, xylose, and mannose. The glucose content of the tender coconut water is slightly lower than that of fasting blood sugar level for humans and hence it's the best drink for diabetic patients.⁸

Virgin Coconut oil- Reduces blood glucose:

The cold pressed virgin coconut oil from the fresh and mature Kernel showed the reduction of blood glucose possibly due to the rich content of lauric acid. It has also a cholesterol-lowering effect.¹⁸

Flowers- Reduces diabetic complications:

Cocos nucifera flowers contain antidiabetic principles which can lower blood glucose level as well as delay the progress of diabetic complications. The in-vivo responses obtained for different extracts of Cocos nucifera flowers are shown in the table no 2. The studies are conducted in either Albino Wistar rats or Sprague Dawley rats. The aqueous extractsof flowers were used to treat diabetic rats in which cardiomyopathy was also induced by doxorubicin. The combination of STZ and doxorubicin increased cardiac marker levels, thereby atherogenic and coronary risks indices, which can be normalized by the 30-day treatment with aqueous extract. The ethanolic extract at 300mg/kg exhibits comparable results with gliclazide 5mg/kg. The flavonoids present in the extract act as free radical scavengers and the alkaloids stimulate the release of insulin from pancreatic beta cells and also have the potential to protect islets from hyperglycemia-mediated oxidative stress. The methanolic and ethanolic extract possess enhanced action than aqueous one, possibly due to the extraction of more active phytoconstituents which tends to release out due to the polarity differences. The least potency of aqueous extract can be also due to the destabilization of any Phytochemicals in water via hydrolysis.¹⁹

Table 2: In-vivo response obtained for Cocos nucifera flowers

Plant part	Animal/ Induction method	Treatment duration	Extraction method	Dose	*In-vivo* response		Reference
Plant part	Animal/ Induction method	Treatment duration	Extraction method	Dose	Glucose level	% Reduction	Reference
Flowers	STZ 45mg/kg i.p 6 groups of five animals	30days	Aqueous	200mg/kg Oral	200mg/dl	23.07%	Bhuvaneshwari R et al¹⁹
			NA	Control	110mg/dl	-
			Doxorubicin control	1.5mg/kg	108mg/dl	-
			STZ+ DOX	45mg/kg STZ+1.5mg/kgDOX	260mg/kg	-
Flowers	Male albino Wistar rats STZ 45mg/kg i.p	30days	Ethanol	300mg/kg /day	149.96 ± 19.81mg/dl	47.69%	S. Saranya et al¹⁴
			Gliclazide	5mg/kg	156.10 ± 16.95	45.55%
			NA	Control	92.55 ± 10.15	-
			NA	DC	286.69+25.94	-
Immature inflorescence	Male Sprague Dawley rats (150-200 g 6 rats/group STZ 45mg/kg	45 days	80%methanol	100mg/kg	112.61±8.70 mg/dl	47.92%	Renjith RS et al¹⁵
				200	107.91±7.90	50.09%
				400	130.22±11.40	39.77%
				DC	216.23+18.50	-
				Control	74.45±6.50	-
Inflorescence	maleWistar rats streptozotocin (45mg/kg; i.p.).	28 days	Ethanolic Extract	250mg/kg	250	50%	Kaur G et al¹¹
			Ethanolic Extract	500mg/kg	230	54%
			Metformin	22.5mg/kg	380	24%
			Metformin +Cn I	250+22.5	140	72%
			NA	DC	500	-
			NA	Control	100	-

Table 3: In-vivo response obtained for other parts of Cocos nucifera

Plant part	Animal/ Induction method	Treatment duration	Extraction method	Dose	*In-vivo* response		Reference
Plant part	Animal/ Induction method	Treatment duration	Extraction method	Dose	Glucose level	% Reduction	Reference
Endocarp	STZ 60mg/kg Male Wistar rats	21 days	Aqueous	200mg/kg	186.5 ±4.6 Mg/dl	40.42%	Tyagi N et al¹⁶
			Aqueous	400mg/kg	165.25 ±5.3	47.20%
			Ethanolic	200mg/kg	158 ±6.6	49.52%
			Ethanolic	400mg/kg	129.75 ±4.8	58.54%
			Glibenclamide	5mg/kg	107.25 ±3.2	65.73%
			NA	DC	313+3.6	-
			NA	Control	90.5 ±1.3	-
Fruit	10%w/v fructose Wistar rats	4 weeks	Household fruit extractor	500mg/kg	75.21±9.29mg/dl	35.55%	Wusu DA et al²⁰
			NA	DC	116.70±9.13	-
			NA	Control	76.33±3.84	-
Husk fiber	Rats weighing between 128 and 152 g Alloxan 150mg/kg i.p	5 days	Methanol fraction	50mg/kg	144.7 ± 5.13	74.87%	Muritala HF et al²¹
			Ethyl acetate fraction	50mg/kg	89.33 ± 6.66	96.46%
			Metformin	50mg/kg	83.00 ± 1.53	98.91%
Mature coconut water	Male Sprague- Dawley rats160-190 6rats/groupAlloxan 150mg/kg BW i.p	45 days	Mature coconut water	1000 mg/kg	129±1.95mg/dl	53.14%	Preetha PP et al¹³
			Glibenclamide	0.6mg/kg	120±2.3mg/dl	56.41%
			NA	DC	275.32+4.25	-
			NA	Control	96.42±2.31	-
Cold pressed virgin coconut oil	8rats/group STZ 60mg/kg	21 days	virgin coconut oil	8ml	207.41±7.12 mg/dl	6.25%	Arumugam MA et al¹⁸
			virgin coconut oil	10ml	133.50±11.3	39.65%
			NA	DC	221.24+4.2	-
			NA	Control	106.4±1.04	-
Virgin coconut oil	Male Sprague-Dawley rats weighing 120 - 150 g 6 animals /group Alloxan 100mg/kg	4 weeks	Virgin coconut oil	7.5ml/kg	132.4 ± 6.911 mg/dl	58.63%	Iranloye B et al²²
			Virgin coconut oil	10ml/kg	131.6 ± 12.2	58.88%
			NA	DC	320	-
			NA	Control	70	-
Coconut product	Alloxan 150mg/kg BW i.pMaleWistar rats	21 days	Coconut milk	4ml/kg	120mg/dl	58.62%	Benjamin A et al²³
			Coconut water	4ml/kg	145	50%
			Milk: water	1:01	130	55.17%
			NA	DC	290	-
			NA	Control	100	-

DC – Diabetic Control; STZ- Streptozotocin; NA- Not applicable; BW- Bodyweight

Table4: In-vitro response of Cocos nucifera

Plant part	Extract	Dose	%Inhibition (In-vitro response)		Reference
			Alpha-amylase	Alpha-glucosidase
Husk fiber	Methanol fraction	50mg/kg	83.84 ± 2.74	-	Muritala HF et al²¹
	Ethyl acetate fraction	50mg/kg	53.08 ± 5.35	-
	Acarbose	50mg/kg	51.70 ± 4.66	-

RESULTS AND DISCUSSION:

The graph depicts the percentage glucose reduction by different extracts of flowers of Cocos nucifera at different doses. Near to 50%, glucose reduction can be brought by non-polar extracts of Cocos nucifera flowers, which indicates the potency of ethanolic and methanolic extract over aqueous one. But, the combination of standard hypoglycaemic agents with extracts possess superior antihyperglycemic activity than extracts or synthetic drugs alone, which otherwise requires higher doses. It clear outs the chances of reducing adverse drug effects of drugs.

Figure 1. Percentage Glucose Reduction of Cocos nucifera flowers

a-Aqueous flowers 200mg/kg, b-Ethanolic flowers 300mg/kg, c- Methanolic immature inflorescense100 mg/kg, d-Methanolic immature inflorescense200 mg/kg, e-Methanolic immature inflorescense 400mg/kg, f-Ethanolicinflorescense 250mg/kg, g-Ethanolic inflorescense500 mg/kg, h-Gliclazide 5mg/kg, i-Metformin 22.5mg/kg, j-Metformin 22.5mg/kg + Ethanolic Inflorescence 250 mg/kg

Figure 2. Percentage glucose reduction of various parts of Cocos nucifera

a-Aqueous endocarp 200mg/kg, b-Aqueous endocarp 400 mg/kg, c-Ethanolic endocarp 200mg/kg, d-Ethanolic endocarp 400mg/kg, e-Fruit 500mg/kg, f-Husk fiber Methanol fraction 50mg/kg, g-Husk fiberEthylacetate fraction 50mg/kg, h-Mature coconut water 1000mg/kg, i-Cold pressed virgin coconut oil 8ml, j-Cold pressed virgin coconut oil 10ml, k-Virgin coconut oil 7.5ml/kg, l-Virgin coconut oil 10ml/kg, m-Coconut milk 4ml/kg, n-Coconut water4ml/kg, o-Milk: Water, p-Metformin 50mg/kg, q-Glibenclamide 0.6mg/kg, r-Glibenclamide 5mg/kg

The activity varies with the difference in the solvent taken for the extraction of plant parts. The order is as follows:Aqueous<Ethanolic<Ethylacetate.

Antihyperglycemic activity proportional to the increasing doses is also found. The ethyl acetate fraction of husk fiber illustrates similar activity level as that of metformin in the above doses. Though the non-polar solvent separates out potent active moieties, its toxicity is still an issue when it comes to the level of marketing and hence the isolation of active constituents in the purest form without any compromise over its activity is essential.The different plant parts vary in their activity as follows: Husk>Flowers>Oil>Endocarp>Milk>Fruit. As coconut water, coconut oil form part of our food and nutrition, the diabetic patients can have these as a part of their daily diet.

CONCLUSION:

The in-vivo and in-vitro studies reveal that Cocos nucifera has got a potential anti-diabetic effect, though it is comparable to that of standard oral hypoglycemic agents. The effect is thought to be due to the presence of various Phytochemicals like flavonoids, phenolicsetc, the antioxidants also accelerate the effect, but further studies are essential for understanding the molecules producing the antidiabetic action and the molecular mechanism of action. It needs further isolation and characterization of compounds. However, Cocos nucifera could create a greater impact in the treatment of diabetes. As the product is completely herbal in origin, and not having major toxic effects, investigation in humans is essential which requires the development of a suitable formulation.

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Received on 21.02.2019 Modified on 23.03.2019

Research J. Pharm. and Tech 2019; 12(8): 3791-3796.

DOI: 10.5958/0974-360X.2019.00649.8

2. Oral Hypoglycemic Medications Kavitha Ganesan1; Senan Sultan. Last Update: September 9, 2018, https://www.ncbi.nlm.nih.gov/books/NBK482386/

2. Oral Hypoglycemic Medications Kavitha Ganesan¹; Senan Sultan. Last Update: September 9, 2018, https://www.ncbi.nlm.nih.gov/books/NBK482386/