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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Renal Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1421551

Anisodamine (654-1/654-2) ameliorates septic kidney injury in rats by inhibiting inflammation and apoptosis

Provisionally accepted
Dong Liu Dong Liu 1Fei Tang Fei Tang 1Li Zhang Li Zhang 1Wan Feng Wan Feng 2Li-Yue Xu Li-Yue Xu 1Jing-Nan Zhang Jing-Nan Zhang 1Xiao-Lan Zhao Xiao-Lan Zhao 1Hui Ao Hui Ao 1,3*Cheng Peng Cheng Peng 1
  • 1 State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
  • 2 Chengdu First Pharmaceutical Co., Ltd, Chengdu, Sichuan Province, China
  • 3 Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China

The final, formatted version of the article will be published soon.

    To investigate the protective effects of anisodamine (654-1/654-2) against acute kidney injury (AKI) in LPS-induced septic shock rats and explore its molecular mechanisms. 56 rats were randomly divided into 8 groups: control, LPS, LPS+654-1, and LPS+654-2 (1.25, 2.5 and 5 mg/kg). The model was evaluated by monitoring MAP, HR, and plasma LD levels. ELISA and biochemical assay kits were used to measure the levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and kidney injury markers (BUN and CRE). Additionally, RNA-seq and bioinformatic analysis were performed to explore the mechanism of action of 654-1/654-2, and verification was conducted by western blotting and RT-PCR. 654-1/654-2 significantly restored the levels of MAP, HR, and plasma LD in septic shock rats. Furthermore, 654-1/654-2 (5 mg/kg) effectively ameliorated LPS-induced kidney structural damage and exhibited a dose-dependent reduction in levels of inflammatory cytokines and kidney injury markers. In addition, RNA-seq, WB, and RT-PCR analyses revealed that 654-1/654-2 exerted its effects by inhibiting the expressions of the NF-κB and MAPK pathways and activating the Pi3K/Akt/Bcl-2 signaling pathway, thereby mitigating AKI. This study suggested that 654-1/654-2 could alleviate AKI in septic shock rats by improving inflammation invasion and cell apoptosis. Notably, 654-1/654-2 collectively suppressed inflammation response through the p38/JNK/AP-1/NF-κB pathway. Additionally, 654-1 Promotes survival signaling via the Pi3K/Akt/Bcl-2 pathway, whereas 654-2 reduces apoptosis through the P53/Bax pathway.These findings provided a theoretical basis for the clinical application of 654-1/654-2 in treating organ damage caused by septic shock.

    Keywords: septic shock, Anisodamine (654-1/654-2), Acute Kidney Injury, Apoptosis, Inflammatory

    Received: 22 Apr 2024; Accepted: 13 Sep 2024.

    Copyright: © 2024 Liu, Tang, Zhang, Feng, Xu, Zhang, Zhao, Ao and Peng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hui Ao, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.