Ethnopharmacological relevance: Rhizoma Anemarrhenae has been used in Asian countries for thousands of years to treat diabetes. Insulin resistance (IR) is the primary cause responsible for type 2 diabetes. The aim of this study was to to assess the hypoglycemic and insulin sensitizing properties of Rhizoma Anemarrhenae extract (TFA) in animal models of insulin resistance and/or diabetes and to delineate modes of action.
Materials and methods: In-vivo studies were performed on STZ-induced diabetic mice and KK-Ay mice, the former of which were given the extract alone or in combination with insulin for 7 days, and the latter of which were given the extract for 8 consecutive weeks. Fasting blood glucose and serum insulin levels were measured. Pancreatic tissue sections were examined using transmission electron micrographs. Further, hyperinsulinemic-euglycemic clamping study was conducted in BCG vaccine-induced insulin resistance rats, and glucose infusion rate was examined. Mechanisms of action were investigated in 3T3-L1 and Hela cells using Western blot analysis.
Results: Our study showed that TFA enhanced the glucose-lowering effects of exogenous insulin administration in STZ-induced diabetic mice. Therapeutic administration of TFA significantly reduced fasting blood glucose, and serum insulin levels, and markedly increased the size and the number of insulin-producing beta cells in KK-Ay mice. Further, hyperinsulinemic-euglycemic clamping study showed that glucose infusion rate was significantly improved in TFA-treated BCG vaccine-induced insulin resistance rats. Study of mechanism of action revealed that TFA increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in 3T3-L1 cells. It activates AMPK in a LKB1-independent manner, providing a unified explanation for the beneficial effects of TFA.
Conclusions: This study that TFA mediates activation of AMPK and improves overall glucose and lipid metabolism in diabetic rodents, highlights the potential utility of TFA for the management of type 2 diabetes.
Keywords: AMP-activated protein kinase; Animal experiment; Anti-diabetic compounds; Bacillus Calmette-Guérin (PubChem CID: 6451); Carboxymethyl Cellulose Sodium (PubChem CID: 6328154); Compound C (PubChem CID: 11524144); Insulin sensitivity; Mangiferin (PubChem CID: 5281647); Neomangiferin (PubChem CID: 6918448); Pentobarbital Sodium (PubChem CID: 14075609); Pioglitazone (PubChem CID: 4829); STO-609 (PubChem CID: 16760660); Streptozocin (PubChem CID: 29327); Wortmannin (PubChem CID: 312145).
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