Total Flavonoids Extracted from <i>Oxytropis falcata</i> Bunge Improve Insulin Resistance through Regulation on the IKK<i>β</i>/NF‐<i>κ</i>B Inflammatory Pathway

Abstract

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