{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:46:13Z","timestamp":1791384373392,"version":"4.3.3"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>56 rats were randomly divided into 8 groups: control, LPS, LPS + 654-1, and LPS + 654-2 (1.25, 2.5 and 5\u00a0mg\/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-1\u03b2, IL-6, and TNF-\u03b1) 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>654-1\/654-2 significantly restored the levels of MAP, HR, and plasma LD in septic shock rats. Furthermore, 654-1\/654-2 (5\u00a0mg\/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-\u03baB and MAPK pathways and activating the Pi3K\/Akt\/Bcl-2 signaling pathway, thereby mitigating AKI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>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-\u03baB 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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1421551","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T12:24:34Z","timestamp":1727439874000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Anisodamine (654-1\/654-2) ameliorates septic kidney injury in rats by inhibiting inflammation and apoptosis"],"prefix":"10.3389","volume":"15","author":[{"given":"Dong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Yue","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Nan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Lan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Ao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.bbcan.2019.04.003","article-title":"The AP-1 transcriptional complex: local switch or remote command?","volume":"1872","author":"Bejjani","year":"2019","journal-title":"Biochimica biophysica acta Rev. cancer"},{"key":"B2","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0140-6736(18)30696-2","article-title":"Sepsis and septic shock","volume":"392","author":"Cecconi","year":"2018","journal-title":"Lancet (London, Engl.)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.molcel.2015.06.029","article-title":"Pin1-Induced proline isomerization in cytosolic p53 mediates BAX activation and apoptosis","volume":"59","author":"Follis","year":"2015","journal-title":"Mol. 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