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This study was therefore designed to investigate the role of AP in SA\u2010AKI, specifically focusing on its underlying anti\u2010inflammatory mechanism. To elucidate the core inflammatory pathology driving SA\u2010AKI, we established an LPS\/zVAD\u2010induced endotoxemia mouse model and a corresponding LPS\/zVAD\u2010stimulated Raw264.7 macrophage model. The renoprotective effect of AP and its underlying mechanisms were systematically investigated using H&amp;E, ELISA, RT\u2010qPCR, Western blot, immunofluorescence, and siRNA silencing. In\n                    <jats:italic>vivo<\/jats:italic>\n                    results suggested that AP improved renal dysfunction and inflammation in LPS\/zVAD\u2010induced septic mice. Furthermore, AP inhibited RIPK1\/RIPK3\/MLKL activation and restored autophagic flux in renal macrophages of SA\u2010AKI mice. In\u00a0vitro, AP suppressed LPS\/zVAD\u2010induced cell death and inflammatory cytokine expression by inhibiting the RIPK1\/RIPK3\/MLKL pathway. Concurrently, AP alleviated LPS\/zVAD\u2010induced autophagy dysfunction by promoting TFEB nuclear translocation, an effect potentially mediated by RIPK1. Consistently, downregulation of TFEB expression in the kidney tissue of septic mice was reversed following AP administration. Collectively, AP demonstrated a therapeutic effect against SA\u2010AKI. Mechanistically, this effect was associated with the modulation of RIPK1, as AP concurrently inhibited necroptosis and restored autophagic flux via TFEB activation, both of which are RIPK1\u2010dependent processes. This dual modulation ultimately attenuated macrophage inflammation.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70309","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:35:32Z","timestamp":1773812132000},"page":"3150-3170","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>Astragalus<\/i>\n                    Polysaccharide Alleviated Septic Associated Acute Kidney Injury Through Dual Mechanisms of\n                    <scp>RIPK1<\/scp>\n                    \u2010Dependent Necroptosis and Autophagy in Macrophage"],"prefix":"10.1002","volume":"40","author":[{"given":"Liwei","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy Shanxi Medical University  Taiyuan China"},{"name":"Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology Shanxi Medical University  Taiyuan China"},{"name":"Key Laboratory of 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