Total alkaloids of Sophora alopecuroides alleviate atherosclerosis by regulating macrophage pyroptosis induced by reactive oxygen species-NLRP3 signaling axis

Cardiovascular and cerebrovascular diseases are common diseases. This study aimed to investigate the role of total alkaloids of Sophora alopecuroides (TASA) in atherosclerosis and exploring the underlying mechanism. Mice were given normal diet (ND), high-fat diet (HFD), and TASA plus ND or HFD. The mice were further administered with NLRP3 shRNA and shControl. After treatment, Hematoxylin and Eosin and Oil Red O staining assessed histological changes. CD31/caspase-1 double staining was detected by fluorescent staining and pyroptosis expression assessed by CD31/TUNEL double staining. Western blot results determined caspase-1 expression in HFD mice. TASA treatment suppressed plaque formation in HFD-fed ApoE-/- mice but insignificantly altered the lesion area in ND-fed ApoE-/- mice. Caspase-1 content and TUNEL positive cells were significantly elevated in mice fed with HFD or ND, whilst advent of TASA further enhanced the activation of caspase-1 in HFD mice. TASA treatment reduced activity of ROS, inhibited NLRP3 inflammasome and regulated macrophage pyroptosis. Inhibition of NLRP3 decreased the lesion area of atherosclerosis and lipid deposition. TASA inhibited the expression of ROS to reduce macrophages necrosis and secretion of inflammatory mediators, thereby alleviating inflammation, delaying plaque formation and stabilizing plaques in atherosclerosis.