{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:03:34Z","timestamp":1790787814676,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T00:00:00Z","timestamp":1626048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81660689"],"award-info":[{"award-number":["81660689"]}],"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":["81760668"],"award-info":[{"award-number":["81760668"]}],"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":["81973555"],"award-info":[{"award-number":["81973555"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:p>The current study focused on the regulatory effects of parthenolide (PNL), a bioactive component derived from <jats:italic>Chrysanthemum parthenium<\/jats:italic> L., against hepatic fibrosis via regulating the crosstalk of toll\u2010like receptor 4 (TLR4) and signal transducer and activator of transcription 3 (STAT3) in activated hepatic stellate cells (HSCs). HSCs or Raw 264.7 macrophages were activated by TGF\u2010\u03b2 or LPS for 1\u00a0hr, respectively, and then treated with PNL, CLI\u2010095 (TLR4 inhibitor), or Niclosamide (STAT3 inhibitor) for the indicated time to detect the crosstalk of TLR4 and STAT3. PNL significantly decreased the expressions of \u03b1\u2010SMA, collagen I, and the ratio of TIMP1 and MMP13 in TGF\u2010\u03b2\u2010activated HSCs. PNL significantly reduced the releases of pro\u2010inflammatory cytokines, including IL\u20106, IL\u20101\u03b2, IL\u20101\u03b1, IL\u201018, and regulated signaling P2X7r\/NLRP3 axis activation. PNL obviously induced the apoptosis of activated HSCs by regulating bcl\u20102 and caspases family. PNL significantly inhibited the expressions of TLR4 and STAT3, including their downstream signaling. PNL could regulate the crosstalk of TLR4 and STAT3, which were verified by their inhibitors in activated HSCs or Raw 264.7 cell macrophages. Thus, PNL could decrease the expressions of fibrosis markers, reduce the releases of inflammatory cytokines, and also induce the apoptosis of activated HSCs. In conclusion, PNL could bi\u2010directionally inhibit TLR4 and STAT3 signaling pathway, suggesting that blocking the crosstalk of TLR4 and STAT3 might be the potential mechanism of PNL against hepatic fibrosis.<\/jats:p>","DOI":"10.1002\/ptr.7214","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T08:44:27Z","timestamp":1626079467000},"page":"5680-5693","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Parthenolide, bioactive compound of <scp><i>Chrysanthemum parthenium<\/i><\/scp> L., ameliorates fibrogenesis and inflammation in hepatic fibrosis via regulating the crosstalk of <scp>TLR4<\/scp> and <scp>STAT3<\/scp> signaling pathway"],"prefix":"10.1002","volume":"35","author":[{"given":"Zhen\u2010Yu","family":"Cui","sequence":"first","affiliation":[{"name":"Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy Yanbian University  Yanji 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