{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:15:24Z","timestamp":1788394524504,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":33,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903913"],"award-info":[{"award-number":["81903913"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Geniposide, a prominent iridoid glycoside derived from\n                    <jats:italic>Gardenia jasminoides J<\/jats:italic>\n                    . Ellis, has garnered attention due to its association with hepatotoxicity despite its well\u2010documented pharmacological efficacy in preclinical and clinical contexts. The NOD\u2010like receptor protein 3 (NLRP3) inflammasome is implicated in numerous pathological conditions, including drug\u2010induced liver injury. This study aims to explore the involvement of the NLRP3 inflammasome in geniposide\u2010induced liver toxicity.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Rats were administered geniposide for 5 days, concurrently treated with or without glibenclamide (GLY), an in vivo inhibitor of NLRP3. In vitro, HL\u20107702 cells were exposed to genipin (a metabolite of geniposide via hepatointestinal circulation), with or without GLY supplement. Liver tissue was examined through pathological sections. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), \u03b3\u2010glutamyl transpeptidase (\u03b3\u2010GT), and total bilirubin (T\u2010Bil) levels were determined using the enzyme plate method. IL\u20101\n                    <jats:italic>\u03b2<\/jats:italic>\n                    and IL\u201018 levels in the supernatant and serum were quantified through ELISA. Apoptosis\u2010associated speck\u2010like protein (ASC), NLRP3, caspase\u20101, pro\u2010IL\u20101\n                    <jats:italic>\u03b2<\/jats:italic>\n                    , and pro\u2010IL\u201018 mRNA levels in cells or the liver were assessed by RT\u2010PCR. Protein levels of ASC, NLRP3, caspase\u20101, pro\u2010IL\u20101\n                    <jats:italic>\u03b2<\/jats:italic>\n                    , and pro\u2010IL\u201018 in cells or the liver were analyzed by Western blot.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Rats treated with geniposide displayed notable liver damage characterized by inflammatory infiltration, elevated serum transaminases, and heightened levels of inflammatory factors IL\u20101\n                    <jats:italic>\u03b2<\/jats:italic>\n                    and IL\u201018. This liver damage was concomitant with NLRP3 inflammasome activation within the liver. Furthermore, genipin induction led to reduced cell viability, increased transaminases in the cell supernatant, and an upsurge in inflammatory factors, resulting in heightened NLRP3 inflammasome expression within the cells. However, GLY effectively curtailed excessive NLRP3 activation, dampened the production of inflammatory factors IL\u20101\n                    <jats:italic>\u03b2<\/jats:italic>\n                    and IL\u201018, and ameliorated liver damage caused by geniposide.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    Our findings collectively elucidate that geniposide induces hepatotoxicity by triggering NLRP3 inflammasome signaling. Inhibition of the inflammasome presents a promising novel therapeutic target for mitigating geniposide\u2010induced hepatotoxicity.\n                  <\/jats:p>","DOI":"10.1155\/mi\/4112856","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T04:21:31Z","timestamp":1738556491000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["NLRP3 Inflammasome Activation Is Involved in Geniposide\u2010Induced 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