PMID- 36660714 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230121 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 10 IP - 24 DP - 2022 Dec TI - Yishen Xiezhuo formula ameliorates the development of cisplatin-induced acute kidney injury by attenuating renal tubular epithelial cell senescence. PG - 1392 LID - 10.21037/atm-22-5415 [doi] LID - 1392 AB - 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 beta-galactosidase (SA-beta-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-beta-Gal-positive senescence cells, down regulated the expression of senescence-related proteins, reduced the release of senescence-related 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. CI - 2022 Annals of Translational Medicine. All rights reserved. FAU - Zhang, Qiaoying AU - Zhang Q AD - Department of Nephrology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. FAU - Qi, Jieying AU - Qi J AD - Department of Nephrology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. FAU - Luo, Qin AU - Luo Q AD - Department of Nephrology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. FAU - Wu, Mengni AU - Wu M AD - Department of Nephrology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. FAU - Zhang, Lili AU - Zhang L AD - Department of Nephrology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. FAU - Qin, Linsen AU - Qin L AD - Department of Nephrology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. FAU - Nie, Xiaoli AU - Nie X AD - Department of Nephrology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC9843381 OTO - NOTNLM OT - Yishen Xiezhuo formula (YSXZ) OT - acute kidney injury (AKI) OT - cell senescence OT - cisplatin (DDP) OT - network pharmacology COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5415/coif). XN reports that this work was supported by the National Natural Science Foundation of China (No. 81774038) and the Natural Science Foundation of Guangdong Province (Nos. 2015A020213300 and 2021A1515011672). The other authors have no conflicts of interest to declare. EDAT- 2023/01/21 06:00 MHDA- 2023/01/21 06:01 PMCR- 2022/12/01 CRDT- 2023/01/20 02:16 PHST- 2022/09/30 00:00 [received] PHST- 2022/12/20 00:00 [accepted] PHST- 2023/01/20 02:16 [entrez] PHST- 2023/01/21 06:00 [pubmed] PHST- 2023/01/21 06:01 [medline] PHST- 2022/12/01 00:00 [pmc-release] AID - atm-10-24-1392 [pii] AID - 10.21037/atm-22-5415 [doi] PST - ppublish SO - Ann Transl Med. 2022 Dec;10(24):1392. doi: 10.21037/atm-22-5415.