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 del Rio, Carmen
A1 Navarrete, Carmen
A1 Collado, Juan A
A1 Bellido, M Luz
A1 Gomez-Cañas, Maria
A1 Pazos, M Ruth
A1 Fernandez-Ruiz, Javier
A1 Pollastro, Federica
A1 Appendino, Giovanni
A1 Calzado, Marco A
A1 Cantarero, Irene
A1 Muñoz, Eduardo
K1 Mice
K1 NIH 3T3 Cells
K1 PPAR gamma
K1 Receptor, Cannabinoid, CB2
K1 Scleroderma, Localized
K1 Signal Transduction
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 vivo 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 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 Nature Publishing Group
YR 2016
FD 2016-01-29
LK http://hdl.handle.net/10668/9845
UL http://hdl.handle.net/10668/9845
LA en
NO del Río C, Navarrete C, Collado JA, Bellido ML, Gómez-Cañas M, Pazos MR, et al. 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 Feb 18;6:21703
NO This work was supported by the MINECO grants RTC-2014-1877-1 and SAF2014-53763-P. We acknowledge Carmen Cabrero-Doncel for her assistance with the article. HEK-293T-CB2 cells were kindly provided by Prof.Akos Heinemann (Institute of Experimental and Clinical Pharmacology, Graz, Austria).
DS RISalud
RD Apr 9, 2025