{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:34:59Z","timestamp":1777872899254,"version":"3.51.4"},"reference-count":41,"publisher":"Frontiers Media SA","issue":"2","license":[{"start":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T00:00:00Z","timestamp":1390435200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:p>\n                    This study investigated a peripheral selective CB\n                    <jats:sub>1<\/jats:sub>\n                    antagonist 3,4,22-3-demethoxycarbonyl-3-hydroxylmethyl-4-deacetyl-vindoline 3,4-thionocarbonate (VD60) that efficiently inhibited hepatic fibrosis with lower psychological side effects. A competitive radiolabeled ligand binding experiment and 3\u2032-5\u2032-cyclic adenosine monophosphate (cAMP) response element-driven luciferase analysis were performed to evaluate the antagonistic activity of VD60. Cell viability and collagen production were examined in the human hepatic stellate cell (HSC) line LX-2 and primary cultured rat HSCs. The antifibrotic effects of VD60 were investigated in a CCl\n                    <jats:sub>4<\/jats:sub>\n                    -induced liver fibrosis mouse model. The concentration of VD60 in the blood and the brain was determined by high-performance liquid chromatography\u2013mass spectrum analysis. Furthermore, the potential underlying mechanisms of VD60 were investigated by Western blot. VD60 selectively competed with the radiolabeled CB\n                    <jats:sub>1<\/jats:sub>\n                    agonist to bind to CB\n                    <jats:sub>1<\/jats:sub>\n                    . VD60 antagonized CB\n                    <jats:sub>1<\/jats:sub>\n                    agonist-induced Akt phosphorylation and increased the accumulation of intracellular cAMP. VD60 strongly reduced the expression of \u03b1\n                    <jats:sub>2<\/jats:sub>\n                    (I) pro-collagen mRNA and exerted potent antiproliferative effects on primary HSCs and LX-2 cells. The inhibition of reactive oxygen species production and phosphorylation of Akt, extracellular-signal-regulated kinase (ERK), and Smad3 may explain the underlying mechanisms behind the antiproliferative effect of VD60. Moreover, the in\u00a0vivo antifibrotic activity of VD60 was confirmed in a CCl\n                    <jats:sub>4<\/jats:sub>\n                    -induced liver fibrosis mouse model. Most importantly, the concentration of VD60 in the peripheral blood was much higher than in the brain, suggesting that VD60 could act as a novel peripheral CB\n                    <jats:sub>1<\/jats:sub>\n                    antagonist to efficiently inhibit hepatic fibrosis and could be used as a lead compound with low brain side effects in peripheral antifibrotic agents.\n                  <\/jats:p>","DOI":"10.1177\/1535370213514922","type":"journal-article","created":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T22:05:26Z","timestamp":1390514726000},"page":"183-192","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["The peripheral cannabinoid receptor 1 antagonist VD60 efficiently inhibits carbon tetrachloride-intoxicated hepatic fibrosis progression"],"prefix":"10.3389","volume":"239","author":[{"given":"Yan","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200093, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-li","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200093, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology, College of Stomatology, Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People\u2019s Republic of 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