Caffeic acid ethanolamide induces antifibrosis, anti-inflammatory, and antioxidant effects protects against bleomycin-induced pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease; its cause is unknown, and it leads to notable health problems. Currently, only two drugs are recommended for IPF treatment. Although these drugs can mitigate lung function decline, neither can improve nor stabilize IPF or the symptoms perceived by patients. Therefore, the development of novel treatment options for pulmonary fibrosis is required. The present study investigated the effects of a novel compound, caffeic acid ethanolamide (CAEA), on human pulmonary fibroblasts and evaluated its potential to mitigate bleomycin-induced pulmonary fibrosis in mice. CAEA inhibited TGF-ß-induced α-SMA and collagen expression in human pulmonary fibroblasts, indicating that CAEA prevents fibroblasts from differentiating into myofibroblasts following TGF-ß exposure. In animal studies, CAEA treatment efficiently suppressed immune cell infiltration and the elevation of TNF-α and IL-6 in bronchoalveolar lavage fluid in mice with bleomycin-induced pulmonary fibrosis. Additionally, CAEA exerted antioxidant effects by recovering the enzymatic activities of oxidant scavengers. CAEA directly inhibited activation of TGF-ß receptors and protected against bleomycin-induced pulmonary fibrosis through inhibition of the TGF-ß/SMAD/CTGF signaling pathway. The protective effect of CAEA was comparable to that of pirfenidone, a clinically available drug. Our findings support the potential of CAEA as a viable method for preventing the progression of pulmonary fibrosis.

A novel caffeic acid derivative prevents renal remodeling after ischemia/reperfusion injury.

Acute kidney disease due to renal ischemia/reperfusion (I/R) is a major clinical problem without effective therapies. The injured tubular epithelial cells may undergo epithelial-mesenchymal transition (EMT). It will loss epithelial phenotypes and express the mesenchymal characteristics. The formation of scar tissue in the interstitial space during renal remodeling is caused by the excessive accumulation of extracellular matrix components and induced fibrosis. This study investigated the effect of caffeic acid ethanolamide (CAEA), a novel caffeic acid derivative, on renal remodeling after injury. The inhibitory role of CAEA on EMT was determined by western blotting, real-time PCR, and immunohistochemistry staining. Treating renal epithelial cells with CAEA in TGF-ß exposed cell culture successfully maintained the content of E-cadherin and inhibited the expression of mesenchymal marker, indicating that CAEA prevented renal epithelial cells undergo EMT after TGF-ß exposure. Unilateral renal I/R were performed in mice to induce renal remodeling models. CAEA can protect against I/R-induced renal remodeling by inhibiting inflammatory reactions and consecutively inhibiting TGF-ß-induced EMT, characterized by the preserved E-cadherin expression and alleviated α-SMA and collagen expression, as well as the alleviated of renal fibrosis. We also revealed that CAEA may exhibits biological activity by targeting TGFBRI. CAEA may antagonize TGF-ß signaling by interacting with TGFBR1, thereby blocking binding between TGF-ß and TGFBR1 and reducing downstream signaling, such as Smad3 phosphorylation. Our data support the administration of CAEA after I/R as a viable method for preventing the progression of acute renal injury to renal fibrosis.