Baicalin alleviates Renal interstitial fibrosis by targeting SIRT1/HIF-1α Signaling Pathway

RENAL INTERSTITIAL FIBROSIS IS A DEFINING FEATURE OF PROGRESSIVE CHRONIC KIDNEY DISEASE: (CKD) with no effective therapeutic drugs in the clinic. Baicalin (BA) is a natural product sourced from Scutellaria baicalensis and has been proven to treat renal fibrosis and multiple kidney diseases. However, the anti-renal fibrosis effects of BA have not been systematically studied, and its underlying mechanisms remain unclear.

This study aims to investigate the role of BA in renal interstitial fibrosis and its potential pharmacological mechanism.

The model of unilateral ureteral obstruction (UUO) mouse and TGF-β-induced cells were employed to evaluate the anti-fibrotic effect of baicalin in vivo and in vitro, respectively. The molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA) were used to verify the relationship of BA and its specific target, Sirtuin 1 (SIRT1). The gene-knockdown cells, RNA-sequence analysis, western blotting assay, and RT-qPCR analysis were performed to clarify the BA-SIRT1 interaction and explore its underlying pharmacological mechanisms.

BA significantly ameliorated renal fibrosis and promoted renal function in UUO mice, with suppressing fibroblast activation in cultured cells. The results of molecular docking, SPR, and CETSA suggested that SIRT1 is a specific target of BA. The anti-fibrotic effects of BA were abolished after SIRT1 was knocked down. The following RNA sequencing and western blotting analysis revealed that BA inhibits the TGF-β1-induced HIF-α signaling pathway via targeting SIRT1.

This study indicated that BA is a SIRT1 agonist in suppressing the HIF-1α signaling pathway to quell renal fibroblast activation and improve renal function in renal interstitial fibrosis.