Isoquercitrin alleviates inflammation in diabetic nephropathy by inhibiting TLR4/NF-κB signaling pathway

OBJECTIVE: The present study aimed to functionally investigate the protective effects and potential mechanisms of action of ISO (Isoquercitrin) in diabetic nephropathy using in vivo and in vitro experiments. METHODS: The mRNA and protein expression levels of markers of fibrosis and inflammation, including TGF-beta 1, Collagen 1, PAI-1, I kappa B alpha, NF-kappa B, and p-NF-Kb, were analyzed by reverse transcription-PCR analysis and western blotting. In addition, histopathological examination was used to confirm the renal injury. ELISA was used to measure biochemical markers of renal injury, including TNF-alpha, IL-1 beta, adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). RESULTS: Our study demonstrated that ISO decreased the levels of glucose, urinary protein, serum creatinine and blood urea nitrogen and alleviated the histopathological abnormalities in the kidney of rats with streptozocin (STZ)-induced D.N. ISO also suppressed STZ-induced activation of NF-kappa B signaling pathway and decreased the STZ-induced increase in the levels of the markers of fibrosis and inflammatory response, including TGF-beta 1, collagen I, plasminogen activator inhibitor-1, TNF-alpha, IL-1 beta, ICAM-1 and VCAM-1 in D.N. rats. ISO also exerted similar protective effects on high glucose (H.G.)-treated HK-2 cells. Finally, exogenous TAK-242, a selective inhibitor of Toll-like receptor 4 (TLR4), enhanced the protective effects of ISO on HG-treated HK-2 cells. CONCLUSION: In summary, our study demonstrated that ISO alleviates D.N. by suppressing fibrosis and inflammatory responses. The protective effects seem to be mediated by inhibiting the activation of the TLR4/NF-kappa B signaling pathway. Our data suggest that ISO has promising therapeutic benefits for patients with D.N.