Circulating metabolites of Borneolum syntheticum(Bingpian)ameliorate atherosclerosis in ApoE−/−mice via inhibiting macrophage foam-cell formation  

作　　者：Rong-rong He Chuan-rui Ma Xin He Yan-xi Dong Hui Li Zi-xuan Chu Xi-he Yang Jia-qi Wang Ting Wang Feng-qing Wang Fei-fei Du Ying Rao Wen-xuan Yu Xiu-mei Gao Guan-wei Fan Chen Cheng Chuan Li 

机构地区：[1]Graduate School,Tianjin University of Traditional Chinese Medicine,Tianjin,301617,China [2]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China [3]First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin,300073,China [4]School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing,210023,China [5]School of Pharmacy,University of Chinese Academy of Sciences,Shanghai,201203,China [6]Zhongshan Institute for Drug Discovery,Zhongshan,528400,China

出　　处：《Acta Pharmacologica Sinica》2025年第3期759-776,共18页中国药理学报(英文版)

基　　金：funded by grants from the National Natural Science Foundation of China(82192912);National Engineering Research Center of TCM Standardization Technology(2023-ZYBZH-10);National Key R&D Program“Strategic Scientific and Technological Innovation Cooperation”Key Project(2022YFE0203600).

摘　　要：Translational pharmacological research on traditional medicines lays the foundation for precisely understanding how the medicines function in the body to deliver therapeutic benefits.Borneolum syntheticum(Bingpian)is commonly used in Chinese herbal medicines for coronary heart disease,but its specific cardiovascular impact remains poorly understood.Isoborneol,a constituent of Bingpian,has been found to reduce lipid accumulation in macrophages in vitro,but its oral bioavailability is limited.This investigation aimed to evaluate anti-atherosclerotic effects of Bingpian,based on understanding its first-pass metabolism.Human subjects orally received an herbal medicine containing Bingpian and their plasma samples were analyzed to identify the major circulating compounds of Bingpian,with the metabolism that was also characterized in vitro and in mice.The identified compounds were evaluated for their ability to inhibit macrophage foam-cell formation induced by oxidized low-density lipoprotein.Furthermore,the anti-atherosclerotic effect of repeatedly dosed Bingpian was assessed in ApoE−/−mice fed a high-fat diet.In human subjects,the major circulating compounds of Bingpian were metabolites,rather than their precursor constituents borneol and isoborneol.These constituents were efficiently absorbed in the intestinal tract but underwent significant first-pass metabolism,involving UGT2B7-mediated glucuronidation into borneol-2-O-glucuronide and isoborneol-2-O-glucuronide,respectively,and CYP2A6/2B6/3A-mediated oxidation both into camphor.Despite their poor membrane permeability,hepatic efflux of borneol-2-O-glucuronide and isoborneol-2-O-glucuronide into the systemic circulation was enhanced by MRP3/4.The circulating metabolites,particularly their combinations,markedly inhibited macrophage foam-cell formation induced by oxidized low-density lipoprotein in vitro.Sub-chronic administration of Bingpian(30 mg·kg^(-1)·d^(-1),i.g.)for 12 weeks significantly decreased atherosclerotic lesion size and enhanced plaque stability

关 键 词：Borneolum syntheticum Bingpian BORNEOL ISOBORNEOL metabolism ATHEROSCLEROSIS 

分 类 号：R285.5[医药卫生—中药学]