{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T21:57:31Z","timestamp":1785794251542,"version":"3.56.0"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:00:00Z","timestamp":1613088000000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Hepatic fibrosis is a consequence of chronic liver diseases. Metalloproteinase and its inhibitor have crucial roles in the resolution of liver fibrosis. The current relevant study is aimed to evaluate the therapeutic effect of <jats:italic>Haematococcus pluvialis<\/jats:italic> (<jats:italic>H. pluvialis)<\/jats:italic> extract, astaxanthin\u2010rich fraction, astaxanthin ester\u2010rich fraction, and <jats:italic>\u03b2<\/jats:italic>\u2010carotene\u2010rich fraction as well as their mechanisms of action in curing hepatic fibrosis induced by thioacetamide (TAA). Liver fibrosis was induced using TAA (intraperitoneal injection, two times a week for 6 weeks), in a rat model and <jats:italic>H. pluvialis<\/jats:italic> extract (200\u2009mg\/kg), and other fractions (30\u2009mg\/kg) were orally administered daily for 4 weeks after the last TAA injection. Based on HPLC analysis, <jats:italic>H. pluvialis<\/jats:italic> extract contains <jats:italic>\u03b2<\/jats:italic>\u2010carotene (12.95\u2009mg\/g, extract) and free astaxanthin (10.85\u2009mg\/g, extract), while HPLC\/ESI\u2010MS analysis revealed that <jats:italic>H. pluvialis<\/jats:italic> extract contains 28 carotenoid compounds including three isomers of free astaxanthin, <jats:italic>\u03b1<\/jats:italic> or <jats:italic>\u03b2<\/jats:italic>\u2010carotene, lutein, 14 astaxanthin mono\u2010esters, 5 astaxanthin di\u2010esters, and other carotenoids. <jats:italic>H. pluvialis<\/jats:italic> and its fractions reduced liver enzymes, nitric oxide, collagen 1, alpha\u2010smooth muscle actin, and transforming growth factor\u2010beta as well as elevated catalase antioxidant activity compared to the TAA group. Also, <jats:italic>H. pluvialis<\/jats:italic> extract and its fractions exceedingly controlled the balance between metalloproteinase and its inhibitor, activated Kupffer cells proliferation, and suppressed liver apoptosis, necrobiosis, and fibrosis. These findings conclude that <jats:italic>H. pluvialis<\/jats:italic> extract and its fractions have an antifibrotic effect against TAA\u2010induced liver fibrosis by regulating the oxidative stress and proinflammatory mediators, suppressing multiple profibrogenic factors, and modulating the metalloproteinase and its inhibitor pathway, recommending <jats:italic>H. pluvialis<\/jats:italic> extract and its fractions for the development of new effective medicine for treating hepatic fibrosis disorders.<\/jats:p>","DOI":"10.1155\/2021\/6631415","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T04:47:31Z","timestamp":1613278051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<i>Haematococcus pluvialis<\/i> Carotenoids Enrich Fractions Ameliorate Liver Fibrosis Induced by Thioacetamide in Rats: Modulation of Metalloproteinase and Its Inhibitor"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4750-3559","authenticated-orcid":false,"given":"Farouk K.","family":"El-Baz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9870-5583","authenticated-orcid":false,"given":"Abeer","family":"Salama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7403-4372","authenticated-orcid":false,"given":"Sami I.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2948-5449","authenticated-orcid":false,"given":"Rania","family":"Elgohary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,12]]},"reference":[{"key":"e_1_2_8_1_2","first-page":"001","volume-title":"Seminars in liver disease","author":"Campana L.","year":"2017"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.33411"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840360710"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.12.008"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1369\/0022155412438104"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.8.5288"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.25589"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2017.44"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjt042"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1119964109"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.5754\/hge11750"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2000.279.2.G245"},{"key":"e_1_2_8_13_2","first-page":"315","article-title":"Hepatic fibrosis: role of matrix metalloproteases and TGFbeta","volume":"141","author":"Sent\u00edes-G\u00f3mez M. 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