Yishen Xiezhuo formula ameliorates the development of cisplatin-induced acute kidney injury by attenuating renal tubular epithelial cell senescence

Abstract

Background: Although cisplatin (DDP) is an important clinical anti-tumor drug, its use is limited by its nephrotoxicity. How to avoid the renal injury incurred by platinum drugs and improve the clinical efficiency of platinum drugs use has become an urgent clinical problem. Previous studies have verified that Chinese medicine has definite effects on acute kidney injury (AKI). Yishen Xiezhuo formula (YSXZ) is a traditional Chinese medicine (TCM) compound which is an effective clinical drug for AKI, but its mechanism remains unclear. Methods: In our research, an AKI model was induced by DDP in human renal tubular epithelial cell (HKC) lines in the in vitro study. The mechanism of the YSXZ on cell senescence was analyzed by Cell Counting Kit-8 (CCK-8), senescence-associated β-galactosidase (SA-β-Gal) staining, western blot, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). Network pharmacology was used to analyze the role of YSXZ against AKI. Results: Compared with the control group, the cells in the DDP intervention group were significantly senescent. Compared with DDP group, YSXZ decreased the number of SA-β-Gal-positive senescence cells, down regulated the expression of senescence-related proteins, reduced the release of senescencerelated secreted phenotypic factors, and reversed the phenomenon of cell cycle S-phase arrest. Network pharmacology and experimental studies showed that the mitogen-activated protein kinase (MAPK) signaling pathway played a central role. Conclusions: Our present results suggested that YSXZ ameliorated the development of DDP-induced AKI by attenuating renal tubular epithelial cell (RTEC) senescence via alleviating the activation of MAPK pathway.

The effect of Astragali Radix-Radix Angelica Sinensis on acute kidney injury: a network pharmacology and molecular docking study

“…It is an independent risk factor for death, with mortality rates of 25% overall ( 2 ). The pathogenesis of AKI involves vasoconstriction, oxidative stress, apoptosis, inflammation, and hypoxia ( 3 - 5 ). At present, except for intermittent hemodialysis and continuous renal replacement therapy, there are no effective drugs or treatment measures that can significantly contribute to AKI prevention.…”

BRD4 plays an antiaging role in the senescence of renal tubular epithelial cells

“…The senescence of renal tubular epithelial cells can be regulated to treat aging-related kidney disease. Therefore, targeting the senescence of renal tubular epithelial cells has become a therapeutic approach for treating kidney injury ( 9 ).…”

Yishen Jiangzhuo decoction attenuates cisplatin‑induced acute kidney injury by inhibiting inflammation, oxidative stress and apoptosis through the TNF signal pathway

“…Cisplatin, also known as cis-diaminedichloroplatinum (CDDP), is an effective drug used to treat numerous types of cancer ( 1 ). However, cisplatin easily accumulates and is biotransformed in the kidneys ( 2 ), which can lead to serious side effects including acute kidney injury (AKI).…”

“…Renal tubular epithelial cells (RTECs) are the primary cellular target in cisplatin-induced AKI ( 1 , 5 ). Cisplatin leads to the injury and death of RTECs by activating complex signaling pathways, including apoptosis, necrosis, inflammation and increased oxidative stress ( 6 ).…”