Insulin-secretagogue, antihyperlipidemic and other protective effects of gallic acid isolated from Terminalia bellerica Roxb. in streptozotocin-induced diabetic rats
Introduction
Diabetes mellitus is a metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. It is well documented that insulin lack at the metabolic level causes derangement of carbohydrate, protein and lipid metabolism which eventually leads to a number of secondary complications such as hyperlipidemia, coronary artery disease, renal failure, stroke, neuropathy, retinopathy and blindness. The prevalence of diabetes for all age-groups worldwide was estimated to be 2.8% in 2000 and 4.4% in 2030. The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030 [1]. Based on WHO recommendations, anti-diabetic agents of plant origin are important for use in traditional medicine [2]. It is estimated that at least 75% of the world's population relies significantly on plant medicines [3].
Terminalia bellerica Roxb. (Combretaceae) is a large deciduous tree which occurs widely in the moist valleys of India and its fruits are most commonly used in Indian traditional systems of medicine [4]. The fruit of T. bellerica has been used in traditional medicine for the treatment of anaemia, asthma, cancer, colic, constipation, diarrhoea, dysuria, headache, hypertension, inflammation and rheumatism [5]. The fruit is reported to have hepatoprotective [6], [7], hypotensive [8], anti-mutagenic [9], antimicrobial and anti-HIV-1 activity [10]. The plant is known to lower the levels of lipid in hypercholesterolemic animals and prevent the development of atherosclerosis and myocardial infarction [11], [12], [13]. Triphala and T. bellerica crude extracts were found to reduce serum glucose level and have marked antioxidant properties in alloxan-induced diabetic rats [14]. In a recent study, the aqueous extract of T. bellerica was found to stimulate insulin secretion in the clonal pancreatic β-cell line [15]. Phytochemically, the fruits of T. bellerica have been reported to contain β-sitosterol, gallic acid, ellagic acid, ethyl gallate, chebulagic acid, galloyl glucose, mannitol, glucose, galactose, fructose, rhamnose [16], arjungenin, belleric acid, bellericoside [17] and three lignans and one flavan [10].
Major ayurvedic plants with therapeutic activity contain gallic acid (GA); however there is a lack of studies on the effect of gallic acid fraction of these plant extracts in STZ-induced diabetic rats. Furthermore, the effect of GA in type 2 diabetic animals is still to be confirmed [18]. We have already reported the antidiabetic and protective effects of T. bellerica fruit extracts on certain biochemical parameters in streptozotocin induced diabetic rats [19]. However there are no reports on the bioassay-guided fractionation and isolation of active principle from the fruits of T. bellerica for the demonstration of its antihyperglycemic and hypolipidemic effects. Therefore the present study was aimed at bioassay-guided fractionation, isolation and identification of active principle(s) from the fruit rind of T. bellerica and assessing the normoglycemic, hypolipidemic and other protective effects of this active principle(s) in STZ-induced diabetic rats.
Section snippets
Plant material
The fruits of T. bellerica Roxb. (Combretaceae) were procured from an authenticated Ayurvedic dealer and were identified and authenticated by Dr. Roseline, Plant taxonomist, Department of Botany, Holy Cross College, Trichy, Tamil Nadu, India. The voucher specimen is preserved in the herbarium of the department. The fruits were dried in shade, chopped and coarsely powdered. The coarse powder was used for extraction.
Isolation and identification of the active compound
One kilogram powder of the fruit rind of T. bellerica Roxb. was soaked in 3 L of
Identification of active compound
A pure pale yellow compound eluted from the most active fraction was subjected to spectral analyses for structural determination. The IR spectrum (Fig. 1A) showed peak for hydroxyl, acid carboxyl and aromatic system: 3355 cm−1 (OH), 2926 cm−1 (CH), 1685 cm−1 (C
O), 1611 cm−1 (CC), 1318 cm−1 (C–O), 1027 cm−1 (C–O), 721 cm−1 (Ar-H). The 1H NMR spectrum in CD3 OD (300 MHz) showed a single peak at δ 7.06 (s,1H) corresponding to H-2 and H-6 which are equivalent and no adjacent protons to couple with. The 13C
Discussion
Streptozotocin is well known for its selective pancreatic islet β-cell cytotoxicity and has been extensively used to induce diabetes mellitus in experimental rat models. Intra-peritoneal administration of streptozotocin in the present study effectively induced diabetes mellitus in rats, which was confirmed by elevated levels of fasting plasma glucose. Although some of the reported antidiabetic plants possess gallic acid as a major chemical compound [28], [29], studies so far have not
Conflict of interest
The authors declare that there are no conflicts of interest.
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