Andrographolide protect against lipopolysacharides induced vascular endothelium dysfunction by abrogation of oxidative stress and chronic inflammation in Sprague–Dawley rats

Abstract

AbstractThe development of heart disease involves interconnected factors such as oxidative stress, inflammation, and vascular dysfunction. Andrographolide (AG), known for its potent antioxidant and anti‐inflammatory properties, has the potential to counteract lipopolysaccharides (LPS)‐induced endothelial dysfunction by reducing oxidative stress and inflammation. Our research aimed to investigate the effects of AG on alleviating vascular endothelium dysfunction, oxidative stress, and inflammation in an experimental model induced by LPS. To create chronic vascular endothelium dysfunction, inflammation, and oxidative stress, rats received weekly injections of LPS via their tail vein over a 6‐week period. The study evaluated the therapeutic effects of orally administered AG (50 mg/kg/day) on diseased conditions. We conducted aortic histology and measured nitric oxide (NO) thresholds, superoxide dismutase (SOD) activity, constitutive nitric oxide (cNOS) activity, and inducible nitric oxide (iNOS) levels, alongside several inflammatory biomarkers. To evaluate endothelial dysfunction, we assessed endothelium‐dependent and endothelium‐independent vasorelaxation in aortas through histopathological and various immunoassays examinations. Vascular Endothelial inflammatory activity was consequently enhanced in LPS groups animals when compared to normal control, also endothelial performance were dependently improved by AG therapy. IL‐1β and tumors necrosis factor levels in the aorta decreased in a dose‐dependent manner after exogenous AG delivery to LPS‐treated rats. However, in current research work aortic SOD activity, NO levels, and cNOS activity increased, whereas aortic malondialdehyde levels and iNOS activity decreased after the AG treatment. These findings suggest that long‐term AG therapy could be considered as a potential therapy to avoid vascular endothelial dysfunction and major nonobstructive coronary artery disease.