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.

Safety evaluation of the aqueous extract Kothala himbutu (Salacia reticulata) stem in the hepatic gene expression profile of normal mice using DNA microarrays.

Kothala himbutu is a traditional Ayurvedic medicinal plant used to treat diabetes. We aimed to evaluate the safety of an aqueous extract of Kothala himbutu stem (KTE) in normal mice. The mice were divided into two groups: one was administered KTE and the other distilled water for 3 weeks. During the test period, the groups showed no significant differences in body weight gain or plasma parameters, such as fasting blood glucose level, oral glucose tolerance test, or aspartate transaminase (AST) or alanine transaminase (ALT) activity. DNA microarray analysis revealed that expression of genes of known function, such as those for the stress response, ribosomal proteins, transcription, cell function, the inflammatory/immune response, and metabolism (xenobiotic, glutathione, etc.) remained largely unaffected by KTE. However some genes such as catechol-o-methyltransferase and succinyl-CoA synthetase were regulated by KTE, indicating that KTE is not toxic to normal mice and might be effective as a functional food.

Glucosamine regulates differentiation of a chondrogenic cell line, ATDC5.

Osteoarthritis (OA) is a slowly progressing chronic joint disease. Glucosamine (GlcN) is a saccharide that is widely used to relieve symptoms associated with OA. However, the mechanism of the effects of GlcN on articular cartilage remains unclear. We studied the effects of GlcN and its analogues, including chitin derivatives included in health supplements containing GlcN, on a chondrogenic cell line, ATDC5. We examined the effects of these saccharides on the proliferation and differentiation of ATDC5 cells. Glucosamine analogues, such as N-acetyl glucosamine and chitobiose, did not affect the proliferation or differentiation of ATDC5 cells. While GlcN did not affect the proliferation of ATDC5 cells, it inhibited their differentiation. Next, we examined whether GlcN affects mineralization and glycosaminoglycan (GAG) production by ATDC5 cells. Mineralization was markedly inhibited by addition of GlcN to the cell culture medium. Moreover, GlcN induced the formation of sulfated GAG in ATDC5. We also analyzed the mRNA levels in ATDC5 cells. GlcN reduced the mRNA levels of Smad2, Smad4 and MGP. GlcN might inhibit expression of MGP mRNA and induce the production of chondroitin sulfate in ATDC5 cells. The mechanism by which GlcN inhibits mineralization may be by regulating the expression of mRNA for the Smad2 and Smad4 chondrogenic master genes.