Oral administration of EHP-101 prevented and inhibited cardiac, renal, pulmonary, and dermal inflammation and fibrosis in a mouse model of Angiotensin II-induced fibrosis.
Does EHP-101 reduce cardiac fibrosis and inflammation in an Angiotensin II-induced mouse model?
EHP-101 demonstrates antifibrotic and anti-inflammatory effects in a mouse model of Angiotensin II-induced cardiac fibrosis, suggesting potential therapeutic utility for fibrotic diseases.
Some cannabinoids showed anti-inflammatory and antifibrotic activities. EHP-101 is an oral lipidic formulation of the novel non-psychotropic cannabidiol aminoquinone VCE-004.8, which showed antifibrotic activity in murine models of systemic sclerosis induced by bleomycin. We herein examined the effect of EHP-101 on cardiac and other organ fibrosis in a mouse model induced by Angiotensin II. VCE-004.8 inhibited TGFβ- and Ang II-induced myofibroblast differentiation in cardiac fibroblasts detected by α-SMA expression. VCE-004.8 also inhibited Ang II-induced ERK 1 + 2 phosphorylation, NFAT activation and mRNA expression of IL1β, IL6, Col1A2 and CCL2 in cardiac fibroblasts. Mice infused with Ang II resulted in collagen accumulation in left ventricle, aortic, dermal, renal and pulmonary tissues; oral administration of EHP-101, Ajulemic acid and Losartan improved these phenotypes. In myocardial tissue, Ang II induced infiltration of T cells and macrophages together with the accumulation of collagen and Tenascin C; those were all reduced by either EHP-101 or Losartan treatment. Cardiac tissue RNA-Seq analyses revealed a similar transcriptomic signature for both treatments for inflammatory and fibrotic pathways. However, the gene set enrichment analysis comparing data from EHP-101 vs Losartan showed specific hallmarks modified only by EHP-101. Specifically, EHP-101 inhibited the expression of genes such as CDK1, TOP2A and MKi67 that are regulated to the E2 factor family of transcription factors. This study suggests that the oral administration of EHP-101 prevents and inhibits cardiac inflammation and fibrosis. Furthermore, EHP-101 inhibits renal, pulmonary and dermal fibrosis. EHP-101 could offer new opportunities in the treatment of cardiac fibrosis and other fibrotic diseases.
García‐Martín et al. (Mon,) conducted a other in Angiotensin II-induced fibrosis and inflammation. EHP-101 vs. Losartan and Ajulemic acid was evaluated on Cardiac and other organ fibrosis and inflammation. Oral administration of EHP-101 prevented and inhibited cardiac, renal, pulmonary, and dermal inflammation and fibrosis in a mouse model of Angiotensin II-induced fibrosis.