Mechanisms of blood glucose-lowering effect of aqueous extract from stems of Kothala himbutu (Salacia reticulata) in the mouse

Ethnopharmacological relevance: Kothala himbutu (Salacia reticulata) is a medicinal plant that has been used in Ayurvedic system of Indian and Sri Lankan traditional medicine to treat diabetes. Aim of the study: This study aimed to clarify the mechanism(s) by which aqueous extracts of Kothala himbutu (KTE) stems decreases fasting blood glucose levels. Materials and methods: Gene expression profiles were assessed by DNA microarray and RT-PCR analyses of RNA from the liver of KK-Ay diabetic mice administered KTE or control distilled water for 4 weeks, and from cultured liver cells treated with freeze-dried KTE (KTED) or selected phenolic compounds. Results: DNA microarray and RT-PCR analyses revealed that gluconeogenic fructose-1,6-bisphosphatase (FBP) was decreased compared with the control in KTE-treated KK-Ay mice. RT-PCR analysis using cultured liver cells treated with KTED and/or actinomycin D or cycloheximide, revealed that KTED directly decreased FBP mRNA levels via destabilization of the mRNA. One compound in KTE, mangiferin, was demonstrated to dose-dependently down-regulate FBP mRNA. Conclusions: These findings suggest that the mangiferin in KTE acts directly on liver cells and down-regulates the gluconeogenic pathway through regulation of FBP expression, thereby decreasing fasting blood glucose levels in mice. Our results demonstrate that gluconeogenic gene regulation is one possible mechanism by which KT exerts its effects in traditional diabetic medicine. (C) 2008 Elsevier Ireland Ltd. All rights reserved.