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Previous reports have shown some beneficial effects of stevioside (SVT) in different diseases, but the ability of SVT to inhibit liver cirrhosis has not been reported. Therefore, we studied the potential of this diterpenoid to inhibit liver cirrhosis induced by thioacetamide, a model that shares many similarities with the human disease, and investigated the possible underlying molecular mechanism using in vivo and in vitro approaches. Cirrhosis was induced in male Wistar rats by chronic thioacetamide administration (200\u00a0mg\/kg) intraperitoneally three times per week. Rats received saline or SVT (20\u00a0mg\/kg) two times daily intraperitoneally. In addition, co\u2010cultures were incubated with either lipopolysaccharide or ethanol. Liver fibrosis, hepatic stellate cells activation, metalloproteinases activity, canonical and non\u2010canonical Smads pathway and expression of several profibrogenic genes were evaluated. Thioacetamide activated hepatic stellate cells and distorted the liver parenchyma with the presence of abundant thick bands of collagen. In addition, thioacetamide up\u2010regulated the protein expression of \u03b1\u2010smooth muscle actin, transforming growth factor\u2010\u03b21, metalloproteinases\u20109,\u20102 and \u201013 and overstimulate the canonical and non\u2010canonical Smad pathways. SVT administration inhibited all of these changes. In vitro<jats:italic>, <\/jats:italic>SVT inhibited the up\u2010regulation of several genes implicated in cirrhosis when cells were exposed to lipopolysaccharides or ethanol. We conclude that SVT inhibited liver damage by blocking hepatic stellate cells activation, down\u2010regulating canonical and non\u2010canonical profibrotic Smad pathways.<\/jats:p>","DOI":"10.1111\/bcpt.13194","type":"journal-article","created":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T15:31:04Z","timestamp":1545147064000},"page":"670-680","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Stevioside inhibits experimental fibrosis by down\u2010regulating profibrotic Smad pathways and blocking hepatic stellate cell activation"],"prefix":"10.1111","volume":"124","author":[{"given":"Sael","family":"Casas\u2010Grajales","sequence":"first","affiliation":[{"name":"Department of Pharmacology Cinvestav\u2010IPN Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Alvarez\u2010Suarez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Cinvestav\u2010IPN Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Ramos\u2010Tovar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Cinvestav\u2010IPN Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Dayana Buend\u00eda\u2010Monta\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Cinvestav\u2010IPN Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Reyes\u2010Gordillo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine and Health Science The George Washington University Medical Center Washington District of Columbia"},{"name":"Lipid Research Laboratory VA Medical Center Washington District of Columbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Camacho","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Cinvestav\u2010IPN Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"Department of Infectomics and Molecular Pathogenesis Cinvestav\u2010IPN Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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