{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:11:40Z","timestamp":1786752700385,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T00:00:00Z","timestamp":1600387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hepatic stellate cell (HSC) activation is an essential event during liver fibrogenesis. Phosphatase and tension homolog deleted on chromosome 10 (PTEN) is a negative regulator of this process. DNA methyltransferase 1 (DNMT1), which catalyzes DNA methylation and subsequently leads to the transcriptional repression of PTEN, is selectively induced in myofibroblasts from diseased livers. Sennoside A (SA), a major purgative constituent of senna and the Chinese herb rhubarb, is widely used in China and other Asian countries as an irritant laxative. SA is reported to improve hepatic steatosis. However, the effect and mechanism of SA on liver fibrosis remain largely unknown. We recently identified a novel strategy for protecting liver fibrosis via epigenetic modification by targeting DNMT1. A Surface Plasmon Resonance (SPR) assay first reported that SA could directly bind DNMT1 and inhibit its activity. Administration of SA significantly prevented liver fibrosis, as evidenced by the dramatic downregulation of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) and type I collagen alpha\u20101 (Col1\u03b11) protein levels in a CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced mouse hepatic fibrosis model and in TGF\u2010\u03b21\u2010activated HSC\u2010T6 cells, in vivo and in vitro. SA decreased the expression of Cyclin D1, CDK, and C\u2010myc, indicating that SA may inhibit the activation and proliferation of TGF\u2010\u03b21\u2010induced HSC\u2010T6. Moreover, SA significantly promoted the expression of PTEN and remarkably inhibited the expression of p\u2010AKT and p\u2010ERK in vitro. Blocking PTEN or overexpressing DNMT1 could reduce the effect of SA on liver fibrosis. These data suggest that SA directly binds and inhibits the activity and that attenuated DNMT1\u2010mediated PTEN hypermethylation caused the loss of PTEN expression, followed by the inhibition of the AKT and ERK pathways and prevented the development of liver fibrosis. Hence, SA might be employed as a promising natural supplement for liver fibrosis drug therapy.\n                  <\/jats:p>","DOI":"10.1096\/fj.202000494rr","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T13:21:46Z","timestamp":1600435306000},"page":"14558-14571","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Sennoside A prevents liver fibrosis by binding DNMT1 and suppressing DNMT1\u2010mediated PTEN hypermethylation in HSC activation and proliferation"],"prefix":"10.1096","volume":"34","author":[{"given":"Hong","family":"Zhu","sequence":"first","affiliation":[{"name":"Anhui Provincial Laboratory of Inflammatory and Immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy Anhui Medical University Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changsheng","family":"He","sequence":"additional","affiliation":[{"name":"Anhui 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