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.