The protective role of Achyranthes aspera extract against cisplatin-induced nephrotoxicity by alleviating oxidative stress, inflammation, and PANoptosis.

Autor: Lin SY; Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei City, 112304, Taiwan. Electronic address: sylin0716@gmail.com., Chang CL; Department of Senior Citizen Welfare and Long-term Care Business, HungKuang University, Taichung City, 43302, Taiwan; Department of Animal Healthcare, HungKuang University, Taichung City, 43302, Taiwan; Department of Biotechnology, HungKuang University, Taichung City, 43302, Taiwan. Electronic address: clchang@sunrise.hk.edu.tw., Liou KT; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei City, 112304, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, 25245, Taiwan; Department of Chinese Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, 114202, Taiwan. Electronic address: kuotong.liou@gmail.com., Kao YK; Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei City, 112304, Taiwan. Electronic address: taobridge@gmail.com., Wang YH; National Taipei University of Nursing and Health Science, Taipei City, 112304, Taiwan. Electronic address: viola9101@gmail.com., Chang CC; Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei City, 112304, Taiwan. Electronic address: sam860528@gmail.com., Kuo TBJ; Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei City, 112304, Taiwan. Electronic address: tbjkuo@gmail.com., Huang HT; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei City, 112304, Taiwan. Electronic address: kk49310953@nricm.edu.tw., Yang CCH; Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei City, 112304, Taiwan. Electronic address: cchyang@nycu.edu.tw., Liaw CC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei City, 112304, Taiwan. Electronic address: liawcc@nricm.edu.tw., Shen YC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei City, 112304, Taiwan; National Taipei University of Nursing and Health Science, Taipei City, 112304, Taiwan. Electronic address: yuhcs@nricm.edu.tw.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2024 Jan 30; Vol. 319 (Pt 1), pp. 117097. Date of Electronic Publication: 2023 Aug 28.
DOI: 10.1016/j.jep.2023.117097
Abstrakt: Ethnopharmacological Relevance: Achyranthes aspera, a widely recognized medicinal plant, is used in various cultures for treating different ailments, including renal dysfunction; however, there is a lack of comprehensive understanding of its protective effects and the underlying signaling networks involved.
Aim of the Study: This study aimed to investigate the molecular mechanisms of the action of A. aspera by employing an integrative approach including functional and tissue imaging as well as comprehensive genomics analysis.
Materials and Methods: Cisplatin-induced nephrotoxicity is a well-established animal model for acute kidney injury (AKI). In this study, we investigated the protective effects and underlying mechanisms of the action of A. aspera water-soluble extract (AAW) on a murine model of cisplatin-induced AKI. The evaluation includes measurements of blood urea nitrogen (BUN) and serum creatinine (SCr) levels, histology examination, and transcriptome analysis using RNA sequencing.
Results: In male ICR mice, oral administration of AAW at doses of 0.5-1.0 g/kg significantly reduced cisplatin-induced nephrotoxicity. This effect included the amelioration of tubular injury, renal fibrosis, and the lowering of BUN and SCr levels. AAW also effectively decreased oxidative markers, such as malondialdehyde (MDA) and nitrotyrosine (NT), along with inflammation markers, including COX-2, iNOS, NLRP3, and pP65NFκB. Moreover, AAW administration induced a dose-dependent increase in the expression of two protective factors, Nrf2 and BcL2, and suppressed apoptosis, as evidenced by reduced levels of truncated caspase 3 (t-Casp3). To explore the underlying molecular mechanisms and signaling networks, next-generation sequencing (NGS) analysis was employed. The results revealed that AAW mitigated apoptosis, necroptosis, and PANoptosis pathways by inhibiting inflammation signaling pathways, such as the TNFα-, NFκB-, NETs-, and leukocyte transendothelial migration pathways. Additionally, AAW was found to enhance protective signaling pathways, including the cGMP/PKG-, cAMP-, AMPK-, and mTOR-dependent activation of autophagy and mitophagy pathways. The primary bioactive compound found in AAW was identified as 20-hydroxyecdysone (0.36%).
Conclusion: Our study demonstrates that AAW reduces cisplatin-induced nephrotoxicity. The protective effects of AAW are attributed to its modulation of multiple molecular signaling networks. Specifically, AAW downregulates genes and signaling pathways associated with oxidative stress and endoplasmic reticulum (ER) stress, inflammation, and PANoptosis. Simultaneously, it upregulates genes and signaling pathways associated with cell survival, including autophagy and mitophagy pathways.
Competing Interests: Declaration of competing interest All authors of this manuscript have made significant contributions to this study, including active participation in the writing process and approval of this submitted version. This research constitutes original work and has not been previously considered for publication in any other journal. We assure you that it will not be submitted elsewhere as long as the Journal of Ethnopharmacology accepts it. Upon acceptance for publication in the Journal of Ethnopharmacology, the worldwide copyright will be transferred to the publisher on behalf of the journal.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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