{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:45:10Z","timestamp":1790959510255,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Fund of Hubei Province","award":["2016CFB638"],"award-info":[{"award-number":["2016CFB638"]}]},{"name":"Hubei Medicine Top-Notch Young Talents","award":["2016CFB638"],"award-info":[{"award-number":["2016CFB638"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2021,8,10]]},"abstract":"<jats:p>Kangxian ruangan (KXRG) is a traditional Chinese medicine (TCM) formula consisting of 12 herbs. TCM syndrome differentiation proposes that KXRG exerts pharmacological effects against nonalcoholic fatty liver disease (NAFLD) fibrosis. This work investigates the effect of KXRG on NAFLD fibrosis in vivo and in vitro. In vivo, the NAFLD fibrosis model was constructed in Wistar rats using methionine- and choline-deficient (MCD) diet, followed by KXRG (0.92\u2009g\/kg\/d) treatment for 8 weeks. In vitro, primary hepatic stellate cells (HSCs) were activated using platelet-derived growth factor (PDGF) and treated with KXRG. Molecular mechanisms underlying fibrosis were investigated. After 8 weeks, compared with the control groups, the histological lesions, degree of fibrosis, and inflammatory reaction increased with the MCD diet as demonstrated by histological changes and increased fibrosis-related (\u03b1-SMA, TGF-\u03b2, COL1A1, and desmin, <jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>P<\/a:mi>\n                        <a:mo>&lt;<\/a:mo>\n                        <a:mn>0.01<\/a:mn>\n                     <\/a:math>\n                  <\/jats:inline-formula>) and inflammation-related factors (TNF-\u03b1, MCP-1, and F4\/80, <jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mi>P<\/c:mi>\n                        <c:mo>&lt;<\/c:mo>\n                        <c:mn>0.01<\/c:mn>\n                     <\/c:math>\n                  <\/jats:inline-formula>), whereas they decreased with KXRG treatment (<jats:inline-formula>\n                     <e:math xmlns:e=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                        <e:mi>P<\/e:mi>\n                        <e:mo>&lt;<\/e:mo>\n                        <e:mn>0.01<\/e:mn>\n                     <\/e:math>\n                  <\/jats:inline-formula>). KXRG not only inhibited the proliferation of activated HSCs and promoted their apoptosis but also resulted in G0-G1 arrest. Furthermore, KXRG suppressed HSC activation (<jats:inline-formula>\n                     <g:math xmlns:g=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\">\n                        <g:mi>P<\/g:mi>\n                        <g:mo>&lt;<\/g:mo>\n                        <g:mn>0.01<\/g:mn>\n                     <\/g:math>\n                  <\/jats:inline-formula>), collagen synthesis (<jats:inline-formula>\n                     <i:math xmlns:i=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\">\n                        <i:mi>P<\/i:mi>\n                        <i:mo>&lt;<\/i:mo>\n                        <i:mn>0.01<\/i:mn>\n                     <\/i:math>\n                  <\/jats:inline-formula>), and \u03b1-SMA expression (<jats:inline-formula>\n                     <k:math xmlns:k=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\">\n                        <k:mi>P<\/k:mi>\n                        <k:mo>&lt;<\/k:mo>\n                        <k:mn>0.01<\/k:mn>\n                     <\/k:math>\n                  <\/jats:inline-formula>) with PDGF stimulation. In both the MCD diet-induced animal model and PDGF-induced cell model, KXRG inhibited TGF-\u03b2 and TLR4 signaling (<jats:inline-formula>\n                     <m:math xmlns:m=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\">\n                        <m:mi>P<\/m:mi>\n                        <m:mo>&lt;<\/m:mo>\n                        <m:mn>0.01<\/m:mn>\n                     <\/m:math>\n                  <\/jats:inline-formula>), similar to corresponding small-molecule inhibitors. These results demonstrated that KXRG might exert suppressive effects against NAFLD fibrosis via regulating TGF-\u03b2 and TLR4 signaling. KXRG may act as a natural and potent therapeutic agent against NAFLD.<\/jats:p>","DOI":"10.1155\/2021\/5649575","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T23:20:11Z","timestamp":1628637611000},"page":"1-14","source":"Crossref","is-referenced-by-count":4,"title":["Antifibrotic Effects of Kangxian Ruangan Capsule on Rats with Nonalcoholic Fatty Liver Fibrosis and Hepatic Stellate Cells through Regulation of TGF-\u03b2 and TLR4 Signaling Pathways"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4581-7730","authenticated-orcid":true,"given":"Liming","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Liver Medicine, Hubei No. 3 People's Hospital, Jianghan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6989-8352","authenticated-orcid":true,"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Liver Medicine, Hubei No. 3 People's Hospital, Jianghan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2750-0227","authenticated-orcid":true,"given":"Dan","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Liver Medicine, Hubei No. 3 People's Hospital, Jianghan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7444-4718","authenticated-orcid":true,"given":"Hongmei","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Liver Medicine, Hubei No. 3 People's Hospital, Jianghan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6199-7428","authenticated-orcid":true,"given":"Kang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Liver Medicine, Hubei No. 3 People's Hospital, Jianghan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8033-6991","authenticated-orcid":true,"given":"Jianjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Liver Medicine, Hubei No. 3 People's Hospital, Jianghan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"issue":"52","key":"1","first-page":"2051","article-title":"[Nonalcoholic fatty liver disease, as a component of the metabolic syndrome, and its causal correlations with other extrahepatic diseases]","volume":"158","author":"T. 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