Steroidal glycoside-rich extract of fenugreek seeds mitigates obesity-induced insulin resistance via attenuation of low-grade inflammation.

Fenugreek seeds, among the top functional foods have traditionally been utilized for the management of diabetes and inflammatory diseases, but the efficacy of steroidal glycoside-rich extract (Met-E) of fenugreek seeds against obesity-induced insulin resistance and inflammation is yet to be clearly elucidated. Adipocytes were used to screen the effect of aqueous (Met-A), ethanolic (Met-E), and hydro-alcoholic (Met-HA) extracts of fenugreek seeds on lipid accumulation. Met-E, the most potent extract was subjected to UHPLC analysis for identification of phytoconstituents and its anti-inflammatory effect using LPS-activated peritoneal macrophages. UHPLC analysis revealed that Met-E extract is rich in steroidal glycoside compounds and able to reduce pro-inflammatory cytokines (TNF, IL-6, IL-1β) production in LPS-activated macrophages. The beneficial effect of Met-E was further evaluated against high-fat diet (HFD) induced insulin resistance (IR) and inflammation in C57BL/6 mice. Experimental pharmacology study in mice demonstrated that oral administration of Met-E significantly reduced body weight gain, blood glucose, serum insulin, pro-inflammatory cytokines, improved lipid profile (TG, TC, LDL-C, HDL-C), and HOMA-IR value. In addition, Met-E significantly improved insulin sensitivity and glucose tolerance in comparison to in HFD mice. Met-E significantly up-regulated mRNA expression of insulin signalling pathway (IRS-1, GLUT4, AKT, PI3K) and down-regulated mRNA expression of inflammatory genes (TNF, IL-6, IL-1β, and NF-κβ). Furthermore, histopathology immunohistochemistry and western blotting studies indicated that Met-E can ameliorate the hypertrophy in adipose tissue by downregulating NF-κβ and upregulate the GLUT4 protein expression. Acute and subacute toxicity revealed the safety of the extract. Met-E, a steroidal glycoside-rich extract from fenugreek seeds alleviates obesity-induced insulin resistance via attenuation of low-grade inflammation. The result of this study suggests the suitability of Met-E, as a functional food for further investigation toward the management of obesity and related complications.