Abstract
Atherosclerosis is a common disease seriously detrimental to human health. Natural products are important sources of therapeutic candidates for atherosclerosis. We here evaluated the effects of ginkgetin on experimental atherosclerosis in rats and explored the underlying mechanisms. Atherosclerosis was induced by high-fat diet for 12 weeks combined with single intraperitoneal injection of vitamin D3 in rats. The atherosclerotic rats were then treated with ginkgetin at 25, 50 and 100 mg/kg/d or simvastatin at 2 mg/kg/d for 8 weeks. Blood and thoracic aortas were collected for analyses of histopathology, lipid deposition, serum biochemistry, matrix metalloproteinases (MMPs), and nitric oxide (NO)/NO synthase (NOS) system. We found that ginkgetin improved thoracic aortic intima structure, reduced intima-media thickness and intima/media ratio, and attenuated lipid deposition in aorta of atherosclerotic rats. Ginkgetin also decreased the serum levels of total cholesterol, triglyceride and low-density lipoprotein cholesterol, but restored the serum levels of high-density lipoprotein cholesterol in atherosclerotic rats. Additionally, ginkgetin reduced the mRNA and protein expression of MMP-2 and MMP-9 in thoracic aortas of rats with atherosclerosis. Further examinations showed that ginkgetin increased the NO and NOS levels in serum and thoracic aortas. Ginkgetin also unregulated the expression of endothelial NOS and downregulated the expression of inducible NOS at both mRNA and protein levels in thoracic aortas of atherosclerotic rats. Altogether, ginkgetin showed therapeutic effects on experimental atherosclerosis associated with improving lipid profile and modulating the MMPs and NO/NOS systems in rats. Ginkgetin could be a promising candidate for the treatment of atherosclerosis.
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