Acute toxicity and the 28-day repeated dose study of a Siddha medicine Nuna Kadugu in rats.

BACKGROUND: Nuna Kadugu (NK), a Siddha medicine prepared from leaves and fruits of Morinda Pubescens, used for the treatment of various skin diseases. Though NK has been widely used for several decades, no scientific report was available on its safety. Present study was undertaken to demonstrate the oral toxicity of NK in Sprague Dawley rats. METHODS: Acute and 28-day repeated oral toxicity studies were performed following OECD test guidelines 423 and 407, respectively, with minor modifications. In acute oral toxicity study, NK was administered at 2000 mg/kg b.wt., p.o and animals were observed for toxic signs at 0, 0.5, 1, 4, 24 h and for next 14 days. Gross pathology was performed at the end of the study. In repeated dose, the 28- day oral toxicity study, NK was administered at 300, 600 and 900 mg/kg b.wt./p.o/day. Two satellite groups (control and high dose) were also maintained to determine the delayed onset toxicity of NK. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. RESULTS: In acute toxicity study, no treatment related death or toxic signs were observed with NK administration. In the repeated dose study, no significant differences in body weight changes, food / water intake, haematology, clinical biochemistry and electrolytes content were observed between control and NK groups. No gross pathological findings and difference in relative organ weights were observed between control and NK treated rats. Histopathological examination revealed no abnormalities with NK treatment. CONCLUSION: Acute study reveals that the LD50 of NK is greater than 2000 mg/kg, b.wt. in fasted female rats and can be classified as Category 5. 28-day repeated oral toxicity demonstrates that the No Observed Adverse Effect Level of NK is greater than 900 mg/kg b.wt./day, p.o in rats. There were no delayed effects in NK satellite group. In conclusion, NK was found to be non-toxic in the tested doses and experimental conditions.

Polyphenols in madhumega chooranam, a Siddha medicine, ameliorates carbohydrate metabolism and oxidative stress in type II diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Present study was undertaken to demonstrate the mode of anti-diabetic action of a polyherbal Siddha Medicine, Madhumega chooranam (MMC). MATERIALS AND METHODS: MMC was fractionated into phenolic (PMMC) and non-phenolic (NPMMC) portions in order to identify bioactive fraction. Study was performed in type II diabetic rats. Role of PMMC and NPMMC on liver glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucokinase and glycogen content were determined. Their role on superoxide dismutase, reduced glutathione and lipid peroxidation were investigated. In addition, their effects on GLUT4 and PPARγ gene expression were studied. Pancreas and liver histopathology was studied using hematoxylin and eosin stain. RESULTS: PMMC improved carbohydrate metabolism by decreasing glucose-6-phosphatase and fructose-1,6-bisphosphatase and increasing glucokinase and glycogen contents in diabetic rats liver. It alleviated oxidative stress by increasing superoxide dismutase, glutathione and decreasing lipid peroxidation content. PMMC up-regulated liver GLUT4 and PPARγ mRNA expression in comparison to the vehicle or NPMMC rats. CONCLUSION: Madhumega chooranam mediates its anti-diabetic action through the inhibition of gluconeogenesis and activation of glycolytic pathways in type II diabetic rats. Increased GLUT4 and PPARγ expressions provide additional information on its glucose uptake/sensitising and hypolipidemic potential. Phenolic components of MMC were found to be the bioactive principles.