Flavocoxid is a mixed extract containing
baicalin and
catechin, and it acts as a dual balanced inhibitor of
cyclooxygenase-1 (COX-1) and COX-2
peroxidase enzyme activities with a significant inhibition of
5-lipoxygenase (5-LOX)
enzyme activity in vitro.
Flavocoxid downregulates gene or
protein expression of several inflammatory markers and exerts also strong
antioxidant activity in several experimental models.
Inflammation and oxidative stress contribute in the pathogenesis of
atherosclerosis. In the present study, an experimental rabbit model of
hypercholesterolemia was developed and the effects of
flavocoxid were evaluated. Rabbits were divided into four groups-normal control, high-
cholesterol-diet (HCD)-fed group, HCD plus
flavocoxid (20 mg/kg/day), or HCD plus
atorvastatin (10 mg/kg/day). Blood samples were collected at the end of the experiment for measuring serum total
cholesterol (TC),
triglycerides (TGs),
high-density lipoprotein cholesterol (HDL-C),
C-reactive protein (CRP),
malondialdehyde (MDA),
reduced glutathione (GSH), and
superoxide dismutase (SOD). In addition, the aorta was removed for measurement of
antioxidant status, vascular reactivity, and intima/media (I/M) ratio. Elevated levels of serum TC, TGs,
LDL-C, and CRP were measured in HCD group. Moreover, HCD caused a significant increase in serum and aortic MDA concomitantly with a reduction in serum and aortic GSH and SOD. Immunohistochemical staining of aortic specimens from HCD-fed rabbits revealed high expression levels of both
tumor necrosis factor-alpha (TNF-α) and nuclear factor (NF)-κB. Rabbits in
flavocoxid group showed significantly lower levels of serum CRP, serum, and aortic MDA and higher levels of serum HDL-C, serum, and aortic GSH and SOD compared to HCD group. HCD-induced elevations in serum TC and
LDL-C did not significantly affected by
flavocoxid treatment. Additionally,
flavocoxid significantly enhanced rabbit aortic endothelium-dependent relaxation to
acetylcholine and decreased the elevated I/M ratio. This effect was confirmed by histopathological examination of the aorta. Moreover,
flavocoxid effectively suppresses the release of inflammatory markers. In conclusion, these findings demonstrated that
flavocoxid would be useful in preventing oxidative stress,
inflammation, and vascular dysfunction induced by HCD.