Soyasaponin A1 and A2 Exert Anti-atherosclerotic Functionality by Decreasing Hypercholesterolemia and Inflammation in High Fat Diet (HFD)-Fed ApoE-/- Mice

Atherosclerosis is a chronic inflammatory disease causing coronary heart attack and stroke. Soyasaponins (SS), the phytochemicals naturally existing in soybean and its products, have been shown to reduce hypercholesterolemia and inflammation which are intimately involved in the genesis and development of atherosclerosis. However, the anti-atherosclerotic functionality of soyasaponins remains unknown. The aim of this study was to investigate the effects of two types of soyasaponin monomers (A1 and A2) supplementation on atherosclerotic plaques formation, serum lipid profiles and inflammation in ApoE gene knockout (ApoE-/-) mice. Sixty 5-week-old ApoE-/- male mice were fed with high fat diet (HFD) and intervened by SSA1 and SSA2 (10 and 20 μmol/kg•BW) or simvastatin (10 μmol/kg•BW) for 24 weeks. The atherosclerotic lesions in aorta, aortic root and innominate artery, the lipid profile and inflammatory markers in serum, and TLR4/MyD88/NF-κB signaling in artery tissues were determined. SSA1 and SSA2 decreased the plaque ratio in aortic root and innominate artery but not in entire aorta. In serum, SSA1 reduced TG, TC and LDL-C, and increased HDL-C; SSA2 decreased TC, TG and LDL-C, but did not affect HDL-C. Meanwhile, SSA1 increased TG; SSA2 increased TC; and both increased bile acids in feces. SSA1 and SSA2 lowered TNF-α, MCP-1 and hs-crp in serum. Furthermore, SSA1 and SSA2 reduced TLR4 and MyD88 expression in aorta and innominate artery, and inhibited NF-κB p65 and IκBα phosphorylation in aorta. These results suggest that SSA1 and SSA2 exert anti-atherosclerotic functionality by decreasing hypercholesterolemia and inflammation in HFD-fed ApoE-/- mice.