Qingxin Lianzi Yin Improves Chronic Kidney Disease by Targeting Ferroptosis via the TLR4/HIF-1α Pathway

Ferroptosis is involved in the pathogenesis of chronic kidney disease (CKD). Qingxin Lianzi Yin (QXLZY) has shown significant advantages in CKD treatment. This investigation intended to explore the impact of QXLZY on ferroptosis in CKD.

The anti-CKD effects of QXLZY were evaluated using the 5/6 nephrectomy-induced rat model and TGF-β1-stimulated HK-2 cells. Oxidative stress and ferroptosis levels were assessed using commercial kits and western blot. The mechanism of QXLZY in CKD treatment was predicted through network pharmacology. TLR4 and HIF-1α levels were detected by western blot. The role of ferroptosis in CKD treatment by QXLZY was explored using the ferroptosis inducer erastin. HK-2 cells overexpressing TLR4 were treated with the HIF-1α inhibitor LW6 to investigate the underlying mechanism. QXLZY components identified through network pharmacology as potentially interacting with TLR4 were validated.

QXLZY effectively alleviated renal injury and inhibited fibrosis and inflammation in CKD models. Moreover, QXLZY markedly suppressed oxidative stress and ferroptosis. However, the anti-CKD effects of QXLZY were partially counteracted by erastin. TLR4 and HIF-1α were identified as potential targets through which QXLZY regulates ferroptosis in CKD. Their levels were notably increased in CKD models but were decreased after QXLZY treatment. Overexpression of TLR4 reversed the anti-CKD effects of QXLZY, and this phenomenon was altered by LW6. Lauric acid (LA) and caprylic acid (CA) were bioactive components within QXLZY regulating the TLR4/HIF-1α pathway in CKD.

QXLZY inhibits ferroptosis by downregulating the TLR4/HIF-1α pathway, thereby alleviating renal fibrosis and improving CKD, with LA and CA potentially playing significant roles.