Total Flavonoids Extracted from Oxytropis falcata Bunge Improve Insulin Resistance through Regulation on the IKKβ/NF-κB Inflammatory Pathway.

Abstract

Background. Insulin resistance (IR) is the main etiology of type 2 diabetes mellitus (T2DM). It has been known that total flavonoid extracts can markedly improve the hypoglycemic symptoms caused by IR. Nevertheless, the relevant molecular mechanism remains unclarified. Aim. This study aimed to investigate the antihyperglycemic effects and mechanism of the total flavonoid extract from Oxytropis falcata Bunge. Methods. STZ-induced T2DM rats (n = 35) were divided into 5 groups: model, low-, medium-, and high-dose total flavonoids, and pioglitazone groups. Ten healthy rats were used as controls. The serum insulin and inflammatory cytokines (MCP-1, TNF-α, and IL-6) level was measured by ELISA. The concentration of IRS-1, p-IRS-1, PKB p-PKB, PI3Kp85, and p-PI3K in skeletal muscles was determined by Western blot. The mRNA level of GLUT4, IκB, and NF-κB in skeletal muscle was detected by qRT-PCR. Results. The treatment of medium- and high-dose total flavonoids significantly reduced the FPG and P2hPG and enhanced insulin level in T2DM rats (P < 0.05). When compared with controls, the serum level of MCP-1, TNF-α, IL-6, IRS-1, and p-IRS-1 was significantly increased in T2DM rats, but the level of PKB, p-PKB, PI3Kp85, and p-PI3K expression was reduced (P < 0.05). The GLUT4 and IκB mRNA expression were significantly decreased, and NF-κB mRNA level was increased (P < 0.05). The treatment of low-, medium-, or high-dose total flavonoids markedly reversed the changes above (P < 0.05). Conclusion. Our study has confirmed the therapeutic effects of total flavonoids from Oxytropis falcata Bunge on IR. The flavonoids might reduce the production of inflammatory cytokines through downregulation of NF-κB expression in inflammatory pathway and regulate the IRS-1-PI3-K-PKB/Akt insulin pathway and thereby increased the GLUT4 expression.