Beneficial effects of capsaicin and dihydrocapsaicin on endothelial inflammation, nitric oxide production and antioxidant activity

Capsaicin and dihydrocapsaicin (DHC) are major pungent capsaicinoids produced in chili peppers. Capsaicin has been previously shown to promote vascular health by increasing nitric oxide (NO) production and reducing inflammatory responses. While capsaicin has been extensively studied, whether DHC exerts cardiovascular benefits through similar mechanisms remains unclear. The current study aimed to investigate the direct effects of DHC on endothelial inflammation, NO release, and free radical scavenging properties. DHC at concentrations up to 50 µM did not affect cell viability, while concentrations of 100 and 500 µM of DHC led to endothelial cytotoxicity. Capsaicin decreased cell viability at concentration of 500 µM. To investigate the effects of capsaicinoids on endothelial activation, we first demonstrated that TNFα induced Ser536 phosphorylation of p65 NFκB, expressions of adhesion molecules, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1, and IL-6 production in primary human endothelial cells. These effects were robustly abrogated by DHC. Consistently, DHC treatment led to a marked reduction in TNFα-mediated monocyte adhesion to endothelial cells. Additionally, NO production was significantly induced by DHC and capsaicin compared to vehicle control. Similar to capsaicin and vitamin C, DHC scavenged DPPH (1,1-diphenyl-2-picrylhydrazyl) free radicals in vitro. Our present study highlights the benefits of DHC and capsaicin treatment on human endothelial cells and provides evidence to support cardiovascular benefits from capsicum consumption.