Danhong Injection Inhibits the Development of Atherosclerosis in Both Apoe-/- and Ldlr-/- Mice

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-alpha (TNF-alpha), 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-alpha, IL-1 beta, IL-6 in macrophages, and human C-reactive protein in hepatocytes, respectively, at the transcriptional level in vitro, DHI also reduced TNF-alpha 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.