{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:55:13Z","timestamp":1792446913712,"version":"4.5.0"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":98,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Pyroptosis is a critical mechanism leading to sepsis\u2010induced acute kidney injury (S\u2010AKI). Allicin, an organosulfur compound extracted from garlic bulbs, protects against S\u2010AKI through its anti\u2010pyroptotic role, but the underlying pathophysiological mechanisms remain largely unknown. In in vivo and in vitro experiments, rats and HK\u20102 cells were induced by caecal ligation and puncture (CLP) and lipopolysaccharides (LPSs), respectively. They were then treated with allicin, insulin\u2010like growth factor\u20101 (IGF\u20101, a PI3K\/AKT agonist), or both. In this study, we found that the levels of p\u2010PI3K, p\u2010AKT, NF\u2010\u03baB, NLRP3, caspase\u20101, gasdermin D (GSDMD)\u2010N, IL\u20101\u03b2, IL\u201018 and lactate dehydrogenase (LDH) were significantly increased, which was accompanied by kidney tissue and HK\u20102 cell pyroptosis, eventually leading to elevated serum creatinine (Scr) and blood urea nitrogen (BUN) levels, increased 7\u2010day mortality and reduced HK\u20102 cell activity in CLP\u2010induced rats and LPS\u2010induced HK\u20102 cells, respectively. Moreover, we observed that allicin significantly reduced the levels of p\u2010PI3K, p\u2010AKT, NF\u2010\u03baB, NLRP3, caspase\u20101, GSDMD\u2010N, IL\u20101\u03b2, IL\u201018 and LDH and inhibited pyroptosis in renal tissues and HK\u20102 cells, ultimately resulting in improved kidney function, 7\u2010day survival, and enhanced HK\u20102 cell activity in CLP\u2010induced rats and LPS\u2010induced HK\u20102 cells. Furthermore, our results demonstrate that agonism of the PI3K\/AKT pathway\u2014by using IGF\u20101\u2014could reverse the abovementioned protective role of allicin, accompanied by increased phosphorylation of PI3K and AKT in vivo and in vitro. Overall, the findings of this study demonstrate that the protective effect of allicin on S\u2010AKI is largely dependent on the inhibition of pyroptosis through the negative regulation of the PI3K\/AKT pathway.<\/jats:p>","DOI":"10.1155\/mi\/5454020","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T08:49:24Z","timestamp":1775724564000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Allicin Attenuates Sepsis\u2010Induced Acute Kidney Injury by Inhibiting Pyroptosis Through Negative Regulation of the PI3K\/AKT Pathway"],"prefix":"10.1155","volume":"2026","author":[{"given":"Yanlei","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0918-0710","authenticated-orcid":false,"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201504-0781OC"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-015-3934-7"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/2431705"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32563-2"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.05.026"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12483"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-023-01928-w"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-022-01640-9"},{"key":"e_1_2_12_9_2","doi-asserted-by":"crossref","DOI":"10.1155\/2024\/4233439","article-title":"MTOR Deletion Alleviates CD4+ T-Cell Dysfunction in Sepsis Through Reducing CTLA4 Accumulation Mediated by Rescuing Autophagy","volume":"2024","author":"Lei X.","year":"2024","journal-title":"Mediators of Inflammation"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109580"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.663216"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9925059"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106118"},{"key":"e_1_2_12_14_2","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.1046523","article-title":"Plants\u2019 Bioactive Secondary Metabolites in the Management of Sepsis: Recent Findings on Their Mechanism of Action","volume":"13","author":"Mahomoodally M. 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