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Dihydromyricetin increases endothelial nitric oxide production and inhibits atherosclerosis through microRNA‐21 in apolipoprotein E‐deficient mice

Dafeng YangDepartment of Cardiovascular Surgery Second Xiangya Hospital Central South University Changsha ChinaZhousheng YangDepartment of Pharmacy The People’s Hospital of Guangxi Zhuang Autonomous Region Nanning ChinaLei ChenDepartment of Pharmacy, Institute of Clinical Pharmacy, Second Xiangya Hospital, Central South University, Changsha, ChinaDa‐Bin KuangDepartment of Pharmacy, Affiliated Changsha Hospital of Hunan Normal University, Changsha, ChinaYang ZouDepartment of Pharmacy The People’s Hospital of Guangxi Zhuang Autonomous Region Nanning ChinaJie LiDepartment of Geriatrics, National Key Clinic Specialty, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, ChinaXu DengDepartment of Cardiology Third Xiangya Hospital Central South University Changsha ChinaSongyuan LuoDepartment of Cardiology Vascular Center Guangdong Cardiovascular Institute Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention Guangdong Provincial People’s Hospital Guangdong Academy of Medical Sciences Guangzhou ChinaJianfang LuoDepartment of Cardiology, Vascular Center, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaJun HeDepartment of General Surgey, Second Xiangya Hospital, Central South University, Changsha, ChinaMiao YanDepartment of Pharmacy, Institute of Clinical Pharmacy, Second Xiangya Hospital, Central South University, Changsha, ChinaGui-Xia HeSchool of Pharmacy Hunan University of Chinese Medicine Changsha ChinaYang DengDepartment of Pharmacy The Third Hospital of Changsha Changsha ChinaRong LiThe Second Affiliated Hospital of University of South China Hengyang ChinaQiong YuanNew Drugs Innovation and Development Institute Department of Pharmacy College of Medicine Wuhan University of Science and Technology Wuhan ChinaYangzhao ZhouDepartment of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, ChinaPei JiangJining Medical UniversityShenglan TanDepartment of Pharmacy, Institute of Clinical Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China

2020en

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Litsenziya: cc-by

ABI

Annotatsiya

Abstract Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata , in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4‐positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E‐deficient ( Apoe − / − ) mice. Yet, those protective effects are abrogated by using NOS inhibitor L‐NAME in Apoe − / − mice received DMY. Mechanistically, DMY decreases microRNA‐21 (miR‐21) and increases its target gene dimethylarginine dimethylaminohydrolase‐1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR‐21 in Apoe − / − mice or miR‐21 overexpression in cultured HUVECs abrogates those DMY‐mediated protective effects. These data demonstrate that endothelial miR‐21‐inhibited DDAH1‐ADMA‐eNOS‐NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management.

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DOI: 10.1111/jcmm.15278

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