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Fibroblast activation is the hallmark of scleroderma and disrupting the intracellular TGF\u03b2 signaling may provide a novel approach to controlling fibrosis. Because of its potential role in modulating inflammatory and fibrotic responses, both PPAR\u03b3 and CB\n                    <jats:sub>2<\/jats:sub>\n                    receptors represent attractive targets for the development of cannabinoid-based therapies. We have developed a non-thiophilic and chemically stable derivative of the CBD quinol (VCE-004.8) that behaves as a dual agonist of PPAR\u03b3 and CB\n                    <jats:sub>2<\/jats:sub>\n                    receptors, VCE-004.8 inhibited TGF\u03b2-induced Col1A2 gene transcription and collagen synthesis. Moreover, VCE-004.8 inhibited TGF\u03b2\u2013mediated myofibroblast differentiation and impaired wound-healing activity. The anti-fibrotic efficacy\n                    <jats:italic>in vivo<\/jats:italic>\n                    was investigated in a murine model of dermal fibrosis induced by bleomycin. VCE-004.8 reduced dermal thickness, blood vessels collagen accumulation and prevented mast cell degranulation and macrophage infiltration in the skin. These effects were impaired by the PPAR\u03b3 antagonist T0070907 and the CB\n                    <jats:sub>2<\/jats:sub>\n                    antagonist AM630. In addition, VCE-004.8 downregulated the expression of several key genes associated with fibrosis, qualifying this semi-synthetic cannabinoid as a novel compound for the management of scleroderma and, potentially, other fibrotic diseases.\n                  <\/jats:p>","DOI":"10.1038\/srep21703","type":"journal-article","created":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T06:15:03Z","timestamp":1455776103000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["The cannabinoid quinol VCE-004.8 alleviates bleomycin-induced scleroderma and exerts potent antifibrotic effects through peroxisome proliferator-activated receptor-\u03b3 and CB2 pathways"],"prefix":"10.1038","volume":"6","author":[{"given":"Carmen","family":"del R\u00edo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Navarrete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan A.","family":"Collado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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