Rosamultin Alleviates LPS-Induced Acute Kidney Injury by Promoting Autophagy and Inhibiting the NF-κB Signaling Pathway.

Abstract

BACKGROUND: Rosamultin (RS), a triterpenoid compound, is the main active component of the traditional Dong ethnic medicine "Madeng'ai". It has been proven to have a significant therapeutic effect on improving renal fibrosis. However, the potential role of RS in the treatment of acute kidney injury (AKI) and the underlying molecular mechanisms remain unclear. Therefore, this study investigates whether RS confers renal protection in AKI and seeks to elucidate its underlying mechanisms. METHODS: The potential mechanism of RS in alleviating AKI was preliminarily predicted through network pharmacology. Lipopolysaccharide (LPS) was used as an inducer to establish AKI models both in vivo and in vitro. The protective effect of RS on AKI was demonstrated through the detection of inflammatory factors, oxidative factors, histological examination, and renal function assessment. Quantitative real-time PCR and Western blotting were employed to investigate the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and autophagic flux. Furthermore, non-targeted metabolomics was conducted to identify differential metabolites between the AKI model and the RS treatment group. RESULTS: RS mitigated LPS-induced inflammatory injury and promoted autophagy, resulting in reduced renal injury in BALB/c mice. In RAW264.7 cells, RS increased the formation of autophagosome and the accumulation of autophagic substrates, while reversing LPS-induced oxidative stress and inflammatory responses. Mechanistically, RS exerts its renoprotective effects through concurrent suppression of the TLR4/NF-κB signaling cascade and induction of autophagic flux. CONCLUSION: The protective effect of RS against LPS-induced renal injury is achieved by inducing autophagy and inhibiting inflammatory responses, oxidative stress and the NF-κB signaling pathway.