{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:35:52Z","timestamp":1792424152316,"version":"4.5.0"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T00:00:00Z","timestamp":1579046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>For hepatic failure, stem cell transplantation has been chosen as an alternative therapy, especially for mesenchymal stem cells (MSCs). The aim of this study was to investigate the effect of eugenol (EUG) on the in vivo antifibrotic activity of adipose tissue-derived MSCs (AT-MSCs) and the underlying mechanism. After characterization of MSCs, rats were divided into five groups, Group 1 (normal control), Group 2 (CCl4), Group 3 (CCl4 + AT-MSCs), Group 4 (CCl4 + EUG) and Group 5 (CCl4 + AT-MSCs + EUG). Biochemical and histopathological investigations were performed. Furthermore, expression of type 1 collagen, \u03b1-SMA, TGF-\u03b21, Smad3 and P-Smad3 was estimated. Compared to the single treatment with AT-MSCs, the combination treatment of the fibrotic rats with AT-MSCs and EUG significantly improved the plasma fibrinogen concentration, IL-10 level and proliferating cell nuclear antigen expression, and also significantly decreased the serum levels of liver enzymes, IL-6, IL-1\u03b2, TNF-\u03b1, type III collagen, hyaluronic acid, hydroxyproline and the TGF-\u03b2 growth factor. Furthermore, the combination treatment significantly decreased the hepatic expression of fibrotic markers genes (Type 1 collagen and \u03b1-SMA) and proteins (\u03b1-SMA, TGF-\u03b21 and phospho-Smad3) more than the treatment with AT-MSCs alone. We demonstrated that the combination treatment with EUG and AT-MSCs strongly inhibited the advancement of CCl4-induced hepatic fibrosis, compared with AT-MSCs alone, through TGF-\u03b2\/Smad pathway inhibition. This approach is completely novel, so more investigations are necessary to improve our perception of the underlying molecular mechanisms accountable for the effects of EUG on the antifibrotic potential of AT-MSCs.<\/jats:p>","DOI":"10.3390\/molecules25020348","type":"journal-article","created":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T11:50:28Z","timestamp":1579089028000},"page":"348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["AT-MSCs Antifibrotic Activity is Improved by Eugenol through Modulation of TGF-\u03b2\/Smad Signaling Pathway in Rats"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0734-5007","authenticated-orcid":false,"given":"Moustafa","family":"Fathy","sequence":"first","affiliation":[{"name":"Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan"},{"name":"Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motonori","family":"Okabe","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba M.","family":"Saad Eldien","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, Jouf University, Jouf 74311, Saudi Arabia"},{"name":"Department of Histology and Cell Biology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiko","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1089\/cell.2013.0090","article-title":"Characterization of amniotic stem cells","volume":"16","author":"Koike","year":"2014","journal-title":"Cell. 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