Astragalus Flavone Ameliorates Atherosclerosis and Hepatic Steatosis Via Inhibiting Lipid-Disorder and Inflammation in apoE-/- Mice

Chuanrui Ma; Jing Zhang; Shu Yang; Yunqing Hua; Jing Su; Yuna Shang; Zhongyan Wang; Ke Feng; Jian Zhang; Xiaoxiao Yang; Hao Zhang; Jingyuan Mao; Guanwei Fan

doi:10.3389/fphar.2020.610550

Astragalus Flavone Ameliorates Atherosclerosis and Hepatic Steatosis Via Inhibiting Lipid-Disorder and Inflammation in apoE^-/- Mice

Front Pharmacol. 2020 Dec 14:11:610550. doi: 10.3389/fphar.2020.610550. eCollection 2020.

Authors

Chuanrui Ma^{1

2}, Jing Zhang^{1

2}, Shu Yang^{3

4}, Yunqing Hua^{1

2}, Jing Su⁵, Yuna Shang⁶, Zhongyan Wang⁷, Ke Feng⁶, Jian Zhang⁸, Xiaoxiao Yang⁹, Hao Zhang^{1

2}, Jingyuan Mao^{1

2}, Guanwei Fan^{1

2}

Affiliations

¹ First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
² Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin, China.
³ Department of Endocrinology, The Second Clinical Medical College, Shenzhen People's Hospital, Jinan University, Shenzhen, China.
⁴ Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China.
⁵ Tianjin State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
⁶ College of Life Sciences, Nankai University, Tianjin, China.
⁷ Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
⁸ Department of Pharmacology, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
⁹ Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.

Abstract

Atherosclerosis is a major pathogenic driver of cardiovascular diseases. Foam cell formation plays a key role in atherogenesis, which is affected by lipid disorder and inflammation. Therefore, inhibition of foam cell formation is a therapeutic approach for atherosclerosis treatment. Total flavone of Astragalus membranaceus (TFA) is extracted from A. membranaceus that has protective effect on cardiovascular disease. However, the effect of TFA on atherosclerosis and the underlying mechanism remains unknown. In this study, we determined whether TFA could inhibit atherosclerosis and uncovered the underlying mechanism. In vivo, ApoE deficient mice were treated with TFA and high-fat diet for 16 weeks. Subsequently, atherosclerotic lesions, hepatic steatosis and associated genes expression in vitro and in vivo were determined. We found that TFA reduced atherosclerotic lesion size and enhanced plaque stability, which might be attributed to improved lipid disorder, reduced inflammation and decreased monocyte adhesion. Mechanistically, TFA inhibited hepatic steatosis via regulating the genes responsible for lipid metabolism, by which ameliorating the lipid disorder. Moreover, in macrophage, TFA reduced the expression of scavenger receptors such as CD36 and SRA; and promoted the expression of ATP-binding cassette transporter A1 and G1 (ABCA1/G1). More importantly, TFA reduced miR-33 expression and dampened NFκB activity, by which de-repressing ABCA1/G1 activity and inhibiting the inflammation. Collectively, TFA can attenuate atherosclerosis via dual suppression of miR-33 and NFκB pathway, and partially through inhibition of scavenger receptors in macrophage. In addition, TFA ameliorates the hepatic steatosis and lipid disorder, which in turn contributes to the amelioration of atherosclerosis, suggesting that TFA might be a novel therapeutic approach for inhibition of atherosclerosis and hepatic steatosis.

Keywords: Astragalus flavone; atherosclerosis; hepatic steatosis; inflammation; lipid disorder.