title: Danhong injection inhibits the development of atherosclerosis in both Apoe⁻/⁻ and Ldlr⁻/⁻ mice.
abstract: Danhong injection (DHI), a certificated Chinese medical product made from radix salviae miltiorrhizae and flos carthami, is prescribed to patients with coronary heart disease in China. To investigate if DHI can inhibit atherosclerosis, apolipoprotein E-deficient (Apoe⁻/⁻) or low-density lipoprotein receptor-deficient (Ldlr⁻/⁻) mice on high-fat diet were divided into 2 groups and received daily intraperitoneal injection of saline and DHI, respectively, for 16 or 20 weeks. After the treatment, mouse aortas were collected to determine lesions, expression of adenosine triphosphate-binding cassette transporter A1 and tumor necrosis factor-α (TNF-α), and macrophage accumulation. Additionally, serum lipid profiles and expression of hepatic HMG-CoA reductase messenger RNA and low-density lipoprotein receptor protein were determined. We observed that DHI inhibited lesions in both Apoe⁻/⁻ and Ldlr⁻/⁻ mice. Associated with the decreased lesions, the aortic adenosine triphosphate-binding cassette transporter A1 expression was increased, whereas the macrophage accumulation was decreased in male Apoe⁻/⁻ mice and both male and female Ldlr⁻/⁻ mice. Although DHI reduced HMG-CoA reductase messenger RNA expression in both female Apoe⁻/⁻ and Ldlr⁻/⁻ mice, it decreased low-density lipoprotein cholesterol levels only in female Apoe⁻/⁻ mice. In addition to attenuation of lipopolysaccharide-induced expression of TNF-α, IL-1β, IL-6 in macrophages, and human C-reactive protein in hepatocytes, respectively, at the transcriptional level in vitro, DHI also reduced TNF-α protein expression in aortic root of both Apoe⁻/⁻ and Ldlr⁻/⁻ mice, suggesting the importance of the anti-inflammatory properties of DHI in the inhibition of lesion development. Taken together, our study demonstrates that DHI inhibits atherosclerosis in both Apoe⁻/⁻ and Ldlr⁻/⁻ mice with various mechanisms, including anti-inflammation. The inhibition of atherosclerosis can be attributed to the cardioprotective properties of DHI.
authors.affiliation: *State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China; †College of Life Sciences, Nankai University, Tianjin, China; ‡Buchang Pharmaceutical Co, Ltd, Xi'an, China; §Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; and ¶Collaborative Innovation Center of Biotherapy, Nankai University, Tianjin, China.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Chen
authors.forename: Mengyang
authors.initials: M
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Zhao
authors.forename: Buchang
authors.initials: B
authors.lastname: Zhao
authors.forename: Lifu
authors.initials: L
authors.lastname: Jia
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Boli
authors.initials: B
authors.lastname: Zhang
authors.forename: Xiumei
authors.initials: X
authors.lastname: Gao
authors.forename: Guangliang
authors.initials: G
authors.lastname: Li
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.forename: Jihong
authors.initials: J
authors.lastname: Han
authors.forename: Yajun
authors.initials: Y
authors.lastname: Duan
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics* / Q000502:physiology*; D050197:Atherosclerosis / Q000139:chemically induced* / Q000235:genetics*; D002460:Cell Line; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood; D005260:Female; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics* / Q000502:physiology*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D001057:Apolipoproteins E; D002784:Cholesterol; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D004958:Estradiol; D011973:Receptors, LDL; C577833:Abca1 protein, mouse; C540581:danhong