Effect of chronic treatment with Enicostemma littorale in non-insulin-dependent diabetic (NIDDM) rats

Abstract

We have studied the effect of aqueous extract of Enicostemma. littorale (2 g/kg p.o.) daily for 6 weeks in neonatal non-insulin-dependent diabetes mellitus (NIDDM) rats. To induce NIDDM a single dose injection of STZ (70 mg/kg; i.p.) was given to the 5-day-old pups. After 3 months of STZ injection when animals were confirmed as diabetic, E. littorale was administered for 6 weeks. Fasting and fed glucose and insulin levels in NIDDM were significantly (P<0.05) higher than control rats and they were significantly decreased by the treatment with E. littorale. Results of the oral glucose tolerance test (OGTT) showed a significant (P<0.05) decrease in both AUC_glucose and AUC_insulin values in NIDDM treated group. Insulin sensitivity (K_ITT) index of NIDDM control was significantly lower as compared with Wistar control and this was significantly (P<0.05) increased after treatment with E. littorale. Treatment with E. littorale also decreased the elevated cholesterol, triglyceride and creatinine levels observed in NIDDM rats. Our data suggest that aqueous extract of E. littorale is a potent herbal antidiabetic. It produces an increase in insulin sensitivity, normalizes dyslipidaemia and provides nephroprotection in diabetic rats.

Introduction

A number of indigenous plants have been widely used for the treatment of diabetes and several other ailments (Mukerji, 1957). Plants like Azaridicta indica, Eugenia jambolana, Momordica charantia, Swertia chirata, Gymnema sylvestre etc. have shown a great potential as antidiabetics and they have been included in various polyherbal preparations. (Dhar et al., 1968, Sharma and Jain, 1960, Dhavan et al., 1980, Hakim et al., 1996).

Enicostemma littorale (Gentianaceae) is a glabrous perennial herb belonging to the family Gentianaceae (Kirtikar and Basu, 1935). It grows throughout India up to 1.5 feet height and more frequently near the sea. It is called as Chota-kirayat or Chota chirayata in Hindi, Mamejavo in Gujarati, Nagajivha in Bengal and Vellarugu or Vallari in Tamil.

Dymock et al. (1893) reported that the aerial part of the plant gave 34% of dry alcoholic extract and 15.7% of ash. Qualitative analysis of the ash revealed the presence of minerals like iron, potassium, sodium, calcium, magnesium, silica, phosphate, chloride, sulphate and carbonate. Five alkaloids, two sterols and volatile oil, have been reported by Natarajan and Prasad (1972). Monoterpene alkaloids like-enicoflavin and gentiocrucine were also isolated (Ghosal et al., 1974, Chaudhuri et al., 1975). The presence of catechins, saponins, steroids and triterpenoids were reported by earlier workers (Retnam and DeBritto, 1988). Betulin, a triterpene sapogenin (m.p. 252–254 °C) was also isolated by earlier workers (Rai and Thakar, 1966, Desai et al., 1966).

Swertiamarin (m.p. 108–111 °C) was isolated from the green viscous mass obtained from an alcoholic extract of the drug treated with ether followed by ethylacetate. (Rai and Thakar, 1966, Desai et al., 1966). Flavonoids and xanthones were found to be present in this plant. Six phenolic acids viz: vanillic acid, syringic acid, p-hydroxy benzoic acid, protocatechuic acid, p-coumaric acid and ferulic acid were also found (Daniel and Sabnis, 1978). Seven flavonoids were isolated from alcoholic extract and their structures were identified as apigenin, genkwanin, isovitexin, swertisin, saponarin, 5-O-glucosylswertisin and 5-O-glucosylisoswertisin (Ghosal and Jaiswal, 1980). Methanol extract of E. littorale was found to contain different aminoacids like l-glutamic acid, tryptophane, alanine, serine, aspartic acid, l-proline, l-tyrosine, threonine, phenyl alanine, l-histidine monohydrochloride, methionine, iso leucine, l-arginine monohydrochloride, DOPA, l-Glycine, 2-amino butyric acid and valine (Retnam and DeBritto, 1988).

This plant has been used as folk medicine for the treatment of diabetes mellitus in Western and Southern India (Gupta et al., 1962). Various Ayurvedic formulations containing E. littorale as one of the ingredients have been shown to produce antihyperglycemic activity in hyperglycemic rat models (Gupta et al., 1962). Ethnomedical studies of North Gujarat (India) reveal the use of hot aqueous extract of E. littorale by the tribal inhabitants for the treatment of diabetes, fever, stomach ache, dyspepsia and malaria in interior part of Gujarat. Although the crude extract of E. littorale has been used in diabetes mellitus by tribal inhabitants in India, a detailed study for antidiabetic property, insulin sensitivity and diabetes induced metabolic alterations is not available. Hence, the present investigation was undertaken to study the effects of chronic treatment with E. littorale on insulin sensitivity and glucose intolerance in STZ-induced NIDDM model of rat. Attempts were made to study the effect of these agents on lipid profile and kidney functions.