{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T02:14:39Z","timestamp":1778811279430,"version":"3.51.4"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060111"],"award-info":[{"award-number":["82060111"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060440"],"award-info":[{"award-number":["82060440"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guizhou Provincial Youth Scientific and Technological Talents Projects","award":["[2021]173"],"award-info":[{"award-number":["[2021]173"]}]},{"name":"Guizhou Provincial Science and Technology Projects","award":["19NSP022"],"award-info":[{"award-number":["19NSP022"]}]},{"name":"Guizhou Provincial Science and Technology Projects","award":["[2020]1Y341"],"award-info":[{"award-number":["[2020]1Y341"]}]},{"name":"National Natural Science Foundation of China in 2020 by the Affiliated Hospital of Guizhou Medical University","award":["Gyfynsfc [2020]-21"],"award-info":[{"award-number":["Gyfynsfc [2020]-21"]}]},{"name":"Marshall Joint Laboratory Project of Affiliated Hospital of Guizhou Medical University","award":["No.N-2021-13"],"award-info":[{"award-number":["No.N-2021-13"]}]},{"name":"National Natural Science Foundation of Guizhou Medical University cultivation project","award":["No.21NSFCP16"],"award-info":[{"award-number":["No.21NSFCP16"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD), which has a high risk of cirrhosis, liver failure, and hepatocellular carcinoma. Piperine (Pip) is an extract of plants with powerful anti-inflammatory effects, however, the function of Pip in NASH remains elusive. Here, we aim to explore the role of Pip in NASH and to find the possible mechanisms.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Methionine and choline-deficient (MCD) diets were used to induce steatohepatitis, methionine- and choline-sufficient (MCS) diets were used as the control. After Pip treatment, H&amp;E staining, Oil Red O staining, hepatic triglyceride (TG) content and F4\/80 expression were performed to analysis liver steatosis and inflammation; Masson\u2019s staining, COL1A1 and \u03b1-SMA were detected liver fibrosis. Lipopolysaccharide (LPS) -treated AML12 cells were used to as the cell model to induce pyroptosis. Then, pyroptosis-related proteins, IL-1\u03b2 and LDH release were detected <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Finally, NF-\u03baB inhibitor, BAY11-7082, was used to further demonstrate the mechanism of Pip in NASH.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The study found that Pip alleviated liver steatosis, inflammation, hepatocyte injury, and fibrosis in mice fed with MCD diets. Moreover, the pyroptosis markers (NLRP3, ASC, caspase-1 p20, and GSDMD), IL-1\u03b2 and LDH release were decreased by Pip treatment. NF-\u03baB activation was suppressed by Pip treatment and pyroptosis-related proteins were down regulated by BAY11-7082.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Pip ameliorates NASH progression, and the therapeutical effect was associated with inhibition of hepatocyte pyroptosis induced by NF-\u03baB.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0301133","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T17:28:28Z","timestamp":1711646908000},"page":"e0301133","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Piperine alleviates nonalcoholic steatohepatitis by inhibiting NF-\u03baB-mediated hepatocyte pyroptosis"],"prefix":"10.1371","volume":"19","author":[{"given":"Suye","family":"Ran","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingyu","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangnan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0809-0621","authenticated-orcid":true,"given":"Yunhuan","family":"Zhen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5409-1356","authenticated-orcid":true,"given":"Qi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"issue":"1","key":"pone.0301133.ref001","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1053\/j.gastro.2005.05.041","article-title":"Natural history of NAFLD: remarkably benign in the absence of cirrhosis","volume":"129","author":"C. 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