Aloperine Alleviates Atherosclerosis by Inhibiting NLRP3 Inflammasome Activation in Macrophages and ApoE^-/- Mice

Atherosclerosis is a chronic cardiovascular disease which is regarded as one of the most common causes of death in the elderly. Recent evidence has shown that atherosclerotic patients can benefit by targeting interleukin-1 beta (IL-1β). Aloperine (ALO) is an alkaloid which is mainly isolated from Sophora alopecuroides L. and has been recognized as an anti-inflammatory disease. Herein, the effect of ALO on atherosclerosis was investigated.

ApoE^-/- mice fed with western diet received ALO once daily. Plaques in the aortas were evaluated using oil red O and hematoxylin & eosin (H&E) staining. Inflammation, lipids and kinases phosphorylation levels were evaluated using ELISA assay and western blot. Pyroptosis was examined by THP-1 cells treated with oxidized low-density lipoprotein (ox-LDL).

Plaque development in aortic sinus and en face aortas were reduced after ALO treatment in ApoE^-/- miceTreatment with ALO ameliorated inflammation and profile of blood lipid. Western blot assay showed that ALO treatment substantially inhibited phosphorylation of p38 and Jun Nterminal kinase (JNK) in aorta of ApoE^-/- mice. Meanwhile, ALO significantly inhibited levels of IL-1β and IL-18 in serum and cleaved caspase-1 and IL-1β expression in aorta of ApoE^-/- mice. Interestingly, ALO mildly increased pro-caspase-1 expression in ApoE^-/- aorta in comparison with saline group. In a dose dependent fashion, ALO treatment markedly inhibited ox-LDL-induced IL-1β and IL-18 levels in THP-1 cells and reduced cleaved caspase-1 and IL-1β expression and caspase-1 activity, while ALO had little effect on nod-like receptor protein containing pyrin-3 (NLRP3), apoptosis associated speck-like protein containing a caspase-1 recruitment domain (ASC).

It is of great practical significance to find the natural product to regulate macrophage pyroptosis, which are key drivers to accelerate the progression of atherosclerosis. ALO could inhibit NLRP3 inflammasome activation in macrophages during atherogenesis, which may serve as a potential candidate for the treatment of atherosclerosis.