Quercetin potentially suppresses renal fibrosis in patients with COVID-19 under hypoxic state

ABSTRACT

Introduction: Renal fibrosis is a main outcome of acute kidney injury in COVID-19 survivors, which is emerging as a global public health concern. Lung damage in the COVID-19 patients leads to acute and chronic hypoxia, which results in inflammation, epithelial-mesenchymal transformation, and fibrosis in kidney. Quercetin is an abundant flavonoid in plant materials. Previous studies indicate that quercetin alleviates the decline of renal function, suppress epithelial to mesenchymal transformation in renal tubules, and reduce fibrosis. The study aimed to explore potential targets of quercetin on treating renal fibrosis in patients with COVID-19-induced hoxpia. Method(s) Gene/protein targets related to COVID-19, renal fibrosis, or quercetin were searched from ten databases, and Cytoscape 3.8.2 was then used to construct the protein-protein interaction network and to identify the core targets. The Metascape platform was used for bioconcentration analysis, while AutoDock Vina was used as the primary molecular docking tool. In vitro, the combination model of hypoxia- and transforming growth factor-beta (TGF-beta)- treated human proximal tubule epithelial cells (HK2 cells) was applied to determine the reno-protective effect of quercetin. Result(s) The network analysis showed that quercetin targeted on TGF-beta pathway in treating COVID-19 induced renal fibrosis. In the intersection PPI network, 115 targets were obtained, and gene enrichment analysis was conducted on 109 key nodes. Molecular docking analysis revealed that quercetin could spontaneously bind to eight targets on the TGF-beta pathway, and the binding energy of TGF-beta1 was 29.82 kJ/mol. The in vitro experiment further showed that quercetin significantly suppressed fibrosis in TGF-beta and hypoxia treated HK2 cells in a dose dependent manner by inhibiting TGF-beta/Smad3 pathway. Conclusion(s) Quercetin could attenuate renal fibrosis in patients with COVID-19 by suppressing TGF-beta/Smad3 pathway. No conflict of interestCopyright © 2023