Investigation On The Anti-Atherogenic Properties Of LongShengZhi Capsule And The Involved Mechanisms

Atherosclerosis?AS?is considered as the main cause of acute cardiovascular events,the leading cause of death in many countries including China.The risk factors for atherosclerosis are disorders of lipid metabolism,endothelial dysfunction and systematic inflammation.Buchang LongShengZhi capsule?LSZ?,a traditional Chinese medicine,has been widely used for treatment of patients with cardiovascular diseases.However,the detailed cardioprotective actions of LSZ and the underlying mechanisms have not been fully investigated.In this study,we used apoE^-/-mice to investigate the function of LSZ in the development of AS and the involved mechanisms.Female apoE^-/-mice?⁸-weeks old?were pre-fed high-fat diet?HFD?for 8 weeks to induce atherosclerosis to a middle stage,and then divided into two groups:control?Ctrl?group and LSZ group.In Ctrl group,mice were continued fed HFD for another 10 weeks,while in LSZ group,mice were fed HFD containing LSZ for 10 weeks.At the end of the experiment,mouse serum,liver and aorta samples were collected for determination of lesions,lipid content in serum and liver,expression of lipid/cholesterol metabolism-related molecules.Our results showed that LSZ played an anti-atherogenic role in a serum lipid lowering-independent manner.The underlying mechanisms by which LSZ reduced atherosclerosis include the following 3 points:first,LSZ decreased macrophage accumulation in the lesion area by activating ABCA1/ABCG1 expression,and enhanced plaque stability by increasing contractile smooth muscle cell and collagen content.Second,LSZ attenuated fatty liver by inhibiting expression of lipogenic genes,such as SREBP1c,while activating expression of triglyceride catabolism genes,such as ATGL.Third,LSZ was demonstrated potent anti-inflammatory effects by decreasing serum TNF-?level as well as inflammatory response in the liver.In vitro,LSZ also decreased the expression of inflammatory cytokines induced by lipopolysaccharide/palmitate.In summary,our study demonstrates that LSZ reduces the progress of atherosclerosis by inhibiting inflammation,decreasing hepatic lipid accumulation as well as foam cell formation and increasing plaque stability.Our study also suggests the base for use of LSZ to patients with cardiovascular diseases.