Total Flavonoids Extracted from Bunge Improve Insulin Resistance through Regulation on the IKK/NF-B Inflammatory Pathway.

. 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. . This study aimed to investigate the antihyperglycemic effects and mechanism of the total flavonoid extract from Bunge. . STZ-induced T2DM rats ( = 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-, 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, IB, and NF-B in skeletal muscle was detected by qRT-PCR. . The treatment of medium- and high-dose total flavonoids significantly reduced the FPG and P2hPG and enhanced insulin level in T2DM rats ( < 0.05). When compared with controls, the serum level of MCP-1, TNF-, 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 ( < 0.05). The GLUT4 and IB mRNA expression were significantly decreased, and NF-B mRNA level was increased ( < 0.05). The treatment of low-, medium-, or high-dose total flavonoids markedly reversed the changes above ( < 0.05). . Our study has confirmed the therapeutic effects of total flavonoids from Bunge on IR. The flavonoids might reduce the production of inflammatory cytokines through downregulation of NF-B expression in inflammatory pathway and regulate the IRS-1-PI3-K-PKB/Akt insulin pathway and thereby increased the GLUT4 expression.