RT Journal Article
T1 The cannabinoid quinol VCE-004.8 alleviates bleomycin-induced scleroderma and exerts potent antifibrotic effects through peroxisome proliferator-activated receptor-γ and CB2 pathways
A1 Río, Carmen del
A1 Gómez Cañas, María
A1 Pazos Rodríguez, María Ruth
A1 Fernández Ruiz, José Javier
A1 Muñoz, Eduardo
AB Scleroderma is a group of rare diseases associated with early and transient inflammation and vascular injury, followed by fibrosis affecting the skin and multiple internal organs. Fibroblast activation is the hallmark of scleroderma, and disrupting the intracellular TGFβ signaling may provide a novel approach to controlling fibrosis. Because of its potential role in modulating inflammatory and fibrotic responses, both PPARγ and CB2 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 PPARγ and CB2 receptors, VCE-004.8 inhibited TGFβ-induced Col1A2 gene transcription and collagen synthesis. Moreover, VCE-004.8 inhibited TGFβ–mediated myofibroblast differentiation and impaired wound-healing activity. The anti-fibrotic efficacy in vivowas 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 PPARγ antagonist T0070907 and the CB2 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
PB Sci Rep
SN 2045-2322
YR 2016
FD 2016-02-18
LK https://hdl.handle.net/20.500.14352/93364
UL https://hdl.handle.net/20.500.14352/93364
LA eng
NO Del  Río  C, Navarrete  C, Collado  JA, Bellido  ML, Gómez-Cañas  M, Pazos   MR, Fernández-Ruiz  J, Pollastro F, Appendino G, Calzado MA, Cantarero I, Muñoz E. The cannabinoid quinol VCE-004.8 alleviates bleomycin-induced scleroderma and exerts potent antifibrotic effects through peroxisome proliferator-activated receptor-γ and CB2 pathways.Sci Rep. 2016, 6:21703.
NO Ministerio de Economía, Comercio y Empresa
DS Docta Complutense
RD 16 abr 2025