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Pharmacol."],"abstract":"<jats:p>Nonalcoholic steatohepatitis (NASH) is a highly prevalent metabolic disorder. Currently, there are no effective pharmacotherapeutic options for preventing and treating NASH. <jats:italic>Portulaca oleracea<\/jats:italic> L. (POL) is an edible herb that has been used for preventing and treating some metabolic disorders in China, but the bioactive constituents in POL and the related mechanisms for treating NASH are still unclear. Here, a comprehensive research strategy was used to identify the core genes and the key constituents in POL for treating NASH, <jats:italic>via<\/jats:italic> integrating bioinformatics analysis and experimental pharmacology both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. The phenotypes and mechanisms of POL were carefully investigated by performing a set of <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> experiments. Bioinformatics analysis suggested that prostaglandin-endoperoxide synthase 2 (PTGS2) was the core target and myricetin (Myr) was the key constituent in POL for treating NASH. In NASH mice model induced by methionine choline deficiency diet, POL significantly alleviated hepatic steatosis and liver injury. In free fatty acids-induced hepatocytes, POL and Myr significantly down-regulated the expression of PTGS2, decreased the number of lipid droplets, and regulated the mRNA expression of lipid synthesis and homeostasis genes, including <jats:italic>FASN<\/jats:italic>, <jats:italic>CPT1a<\/jats:italic>, <jats:italic>SERBP1c<\/jats:italic>, <jats:italic>ACC1<\/jats:italic>, and <jats:italic>SCD1<\/jats:italic>. In lipopolysaccharide-induced macrophages, POL and Myr significantly reduced the expression of PTGS2 and blocked the secretion of inflammatory mediators TNF-\u03b1, IL-6, and IL-1\u03b2. Further investigations demonstrate that Myr acts as both suppressor and inhibitor of PTGS2. Collectively, POL and its major component Myr can ameliorate NASH <jats:italic>via<\/jats:italic> down-regulating and inhibiting PTGS2, suggesting that POL and Myr can be developed as novel medicines for treating NASH.<\/jats:p>","DOI":"10.3389\/fphar.2021.818227","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T05:44:57Z","timestamp":1642571097000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Deciphering the Effective Constituents and Mechanisms of Portulaca oleracea L. for Treating NASH via Integrating Bioinformatics Analysis and Experimental Pharmacology"],"prefix":"10.3389","volume":"12","author":[{"given":"Xiaoli","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiren","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanghao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruoxi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawen","family":"You","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanting","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunhao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanming","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangbo","family":"Ge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjie","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"139","DOI":"10.3390\/molecules24010139","article-title":"Anti-inflammatory and Anti-oxidant Activity of Portulaca Oleracea Extract on LPS-Induced Rat Lung Injury","volume":"24","author":"Baradaran Rahimi","year":"2019","journal-title":"Molecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The Multiple-Hit Pathogenesis of Non-alcoholic Fatty Liver Disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"B3","doi-asserted-by":"publisher","first-page":"787152","DOI":"10.1155\/2012\/787152","article-title":"Myricetin Increases Hepatic Peroxisome Proliferator-Activated Receptor \u03b1 Protein Expression and Decreases Plasma Lipids and Adiposity in Rats","volume":"2012","author":"Chang","year":"2012","journal-title":"Evid. 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