PMID- 34385105 OWN - NLM STAT- MEDLINE DCOM- 20220106 LR - 20220106 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 142 DP - 2021 Oct TI - Panax notoginseng saponins reduces the cisplatin-induced acute renal injury by increasing HIF-1alpha/BNIP3 to inhibit mitochondrial apoptosis pathway. PG - 111965 LID - S0753-3322(21)00747-2 [pii] LID - 10.1016/j.biopha.2021.111965 [doi] AB - Cisplatin (CDDP) may induce apoptosis of renal tubular epithelial cells (RTEC) and cause CDDP-induced acute kidney injury (CAKI) during cancer treatment, but yet lack of preventive measures and effective treatment. As a new Chinese herbal preparation, Panax notoginseng saponins (PNS) has been found to mitigate CDDP-induced CAKI through elevating the expression of HIF-1alpha in the rat model, according to the data from our previous works. However, the underlying link between HIF-1alpha and apoptosis has not been well elucidated. The current study as a follow-up work, was aimed to reveal if PNS improves CAKI through HIF-1alpha-dependent apoptosis. A stably HIF-1alpha-knockdown human proximal tubular epithelial cell (HK-2) line was established by transfecting a HIF-1alpha-siRNA into HK-2 cells. Cell viability, mitochondrial function, cell apoptosis ratio and the expression of apoptosis-associated proteins (Cyt C, Bcl2, Bax, caspases 3) were determined. In order to elucidate the underlying mechanism, the expression of HIF-1alpha and BNIP3 were assessed. Our results showed that treatment of PNS rescued the cell viability of CDDP-injured HK-2 or HIF-1alpha-knockdown HK-2 cells, and increased the expression levels of ATP and MMP in HK-2 or HIF-1alpha-knockdown HK-2 cells which were reduced by CDDP. Moreover, PNS treatment decreased the CDDP or CDDP plus HIF-1alpha-knockdown-induced elevation of apoptosis and apoptosis-associated protein expressions. These findings demonstrate that PNS reduces CAKI through increasing HIF-1alpha to inhibit mitochondrial apoptosis pathway. Hence, we suggest PNS as a protective and therapeutic new drug for CDDP treatment of cancers, which might have significant meaning of further research and application potential. CI - Copyright (c) 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Li, Qingqing AU - Li Q AD - Postgraduate, Pharmacy Department, the first affiliated hospital of Guangxi Medical University, Nanning, China. FAU - Zhang, Yansong AU - Zhang Y AD - Postgraduate, Pharmacy Department, the first affiliated hospital of Guangxi Medical University, Nanning, China. FAU - Yang, Yufang AU - Yang Y AD - Pharmacy Department, the first affiliated hospital of Guangxi Medical University, Nanning, China. Electronic address: yufangyang@gxmu.edu.cn. FAU - Huang, Songqing AU - Huang S AD - Postgraduate, Pharmacy Department, the first affiliated hospital of Guangxi Medical University, Nanning, China. FAU - Zou, Xiaoqin AU - Zou X AD - Pharmacy Department, the first affiliated hospital of Guangxi Medical University, Nanning, China. FAU - Wei, Congying AU - Wei C AD - Postgraduate, Pharmacy Department, the first affiliated hospital of Guangxi Medical University, Nanning, China. FAU - Liang, Taolin AU - Liang T AD - Postgraduate, Pharmacy Department, the first affiliated hospital of Guangxi Medical University, Nanning, China. FAU - Zhong, Xiaobin AU - Zhong X AD - Regenerative Medicine Research Center of Guangxi Medical University, Nanning, China. LA - eng PT - Journal Article DEP - 20210809 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Antineoplastic Agents) RN - 0 (BNIP3 protein, human) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Membrane Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Saponins) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Acute Kidney Injury/chemically induced/*prevention & control MH - Animals MH - Antineoplastic Agents/toxicity MH - Apoptosis/drug effects MH - Cell Line MH - Cell Survival/drug effects MH - Cisplatin/*toxicity MH - Epithelial Cells/drug effects/pathology MH - Gene Knockdown Techniques MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/genetics MH - Kidney Tubules, Proximal/cytology/drug effects/pathology MH - Membrane Proteins MH - Mitochondria/drug effects/pathology MH - Panax notoginseng/*chemistry MH - Proto-Oncogene Proteins MH - Rats MH - Saponins/isolation & purification/*pharmacology OTO - NOTNLM OT - Cisplatin-induced acute kidney injury OT - HIF-1alpha-siRNA OT - Mitochondrial apoptosis pathway OT - Panax notoginseng saponins EDAT- 2021/08/14 06:00 MHDA- 2022/01/07 06:00 CRDT- 2021/08/13 06:10 PHST- 2021/06/14 00:00 [received] PHST- 2021/07/22 00:00 [revised] PHST- 2021/07/22 00:00 [accepted] PHST- 2021/08/14 06:00 [pubmed] PHST- 2022/01/07 06:00 [medline] PHST- 2021/08/13 06:10 [entrez] AID - S0753-3322(21)00747-2 [pii] AID - 10.1016/j.biopha.2021.111965 [doi] PST - ppublish SO - Biomed Pharmacother. 2021 Oct;142:111965. doi: 10.1016/j.biopha.2021.111965. Epub 2021 Aug 9.