{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T01:23:29Z","timestamp":1790558609758,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T00:00:00Z","timestamp":1650585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770497, 82070829 and 81600389"],"award-info":[{"award-number":["81770497, 82070829 and 81600389"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2017T100757"],"award-info":[{"award-number":["2017T100757"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and Technology (National Key R&amp;D Program)","award":["2018YFA0800600"],"award-info":[{"award-number":["2018YFA0800600"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Procyanidin B2 (PCB2), a natural flavonoid, has been demonstrated to exert anti-oxidation and anti-inflammatory effects on hepatic diseases. Increasing evidence shows the hepatoxicity of nicotine. However, whether PCB2 protects against nicotine-induced hepatoxicity and the underlying mechanisms remains uncharacterized. Here, we reported that nicotine promoted hepatocyte pyroptosis, as evidenced by the elevation of propidium iodide (PI)-positive cells, the activation of Caspase-1 and gasdermin D (GSDMD), the enhanced expression of NOD-like receptor containing pyrin domain 3 (NLRP3) and the increased release of lactate dehydrogenase (LDH), interleukin (IL)-1\u03b2 and IL-18. The silencing of GSDMD by small interfering RNA (siRNA) efficiently inhibited the release of LDH and the secretion of IL-1\u03b2 and IL-18. In addition, rosiglitazone (RGZ) prevented hepatocyte pyroptosis induced by nicotine. Furthermore, we showed that PCB2 attenuated nicotine-induced pyroptosis through the activation of peroxisome proliferator-activated receptor-\u03b3 (PPAR\u03b3) in hepatocytes. Moreover, administration of PCB2 ameliorated liver injury and hepatocyte pyroptosis in nicotine-treated mice. Hence, our findings demonstrated that PCB2 attenuated pyroptosis and liver damage in a PPAR\u03b3-dependent manner. Our results suggest a new mechanism by which PCB2 exerts its liver protective effects.<\/jats:p>","DOI":"10.3390\/nu14091756","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T21:39:45Z","timestamp":1650749985000},"page":"1756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Procyanidin B2 Attenuates Nicotine-Induced Hepatocyte Pyroptosis through a PPAR\u03b3-Dependent Mechanism"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2733-0013","authenticated-orcid":false,"given":"Jia","family":"Liu","sequence":"first","affiliation":[{"name":"Cardiovascular Research Center, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases, Xi\u2019an Jiaotong University, Ministry of Education of China, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyu","family":"Yao","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinya","family":"Xie","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Cui","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Jiang","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Du","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baochang","family":"Lai","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8962-8280","authenticated-orcid":false,"given":"Lei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases, Xi\u2019an Jiaotong University, Ministry of Education of China, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanping","family":"Wang","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.amepre.2016.12.024","article-title":"A Safer, Healthier U.S.: The Centers for Disease Control and Prevention, 2009\u20132016","volume":"52","author":"Frieden","year":"2017","journal-title":"Am. 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