This study described for the first time that scutellarin has hypocholesterolimic effect and
is orally active. In the present study, we Buy Cheap Clomid have illustrated that oral scutellarin
administration significantly reduced serum total cholesterol and increased serum
HDL/LDL ratio. In addition, the elevated atherogenic index induced by atherogenic diet
was reversed thus suggesting atheroscleroprotection by scutellarin. Although the testing
dosage for scutellarin was up to 100 mg/kg/day, it can be considered as non-toxic for the
fact that intraperitoneal LD50 values in mice is 2402 mg/kg . To evaluate the
applicability of the current animal model, simvastatin (positive control) was used. Buy Clomid And Nolvadex It is a
potent hypocholesterolemic and hypolipidemic Cheap Clomid Online drug of statin series and is commonly for
the treatment of coronary heart disease, hypercholesterolemia and hyperlipidemia . In
this study, simvastatin has been shown to improve serum lipid profile and atherogenic
index similar to the effects seen with scutellarin. Buy Clomid In The Uk However, the effects of simvastatin in
the present study were associated with an increase in Where Can I Buy Clomid In The Uk HDL level but no change in LDL
level in animals fed with atherogenic diet. This is different from the function of statins in
lowering LDL. This warrants further study in the current experimental setting.
In the current study, the HCD had abnormal serum lipid levels with significantly
increased total cholesterol and LDL but no significant changes in triglyceride and HDL
levels. This is consistent with previous studies with similar experimental settings [3,16].
In fact, elevated plasma total cholesterol and LDL levels are How To Order Clomid Online significant enough to
demonstrate the atherogenic effect of the model since both parameters play a significant
role in atherosclerosis development and subsequent coronary heart disease .
Hypercholesterolemia and atherosclerosis have a close relationship with vascular
dysfunction . The present findings showed endothelial dysfunction in aortic rings from
hypercholesterolemic rats. Vascular relaxation in response to acetylcholine was clearly
blunted in aortas from the HCD. This provides supporting evidence to other studies
where hypercholesterolemia and early stages of atherosclerosis in experimental animals
and humans, the most common vascular functional abnormality is a reduction of
endothelium-dependent relaxation . Scutellarin could prevent the high cholesterol
diet-induced reduction of eNOS gene expression. This in turn, increased the
acetylcholine-induced nitrate/nitrite production and acetylcholine-induced vasorelaxation
in aortic rings dose dependently.
NO responds to various pathophysiological stimuli in order to protect the integrity of the
vasculature . It is rapidly oxidized to nitrite/nitrate. The measurement of plasma
nitrite/nitrate after an overnight fast was used as an index of NO Clomid Order Online synthase (NOS) activity
. Indeed, either activation or inhibition of NOS activity was associated with
corresponding increases or decreases in circulation nitrite concentrations . However,
it should be noted that approximately 70% of Buy Clomid Uk plasma nitrite has been shown to be derived
from NOS activity in the endothelium . To enhance the accuracy of NOS activity
estimation, we adopted a method to measure acetylcholine-induced nitrate/nitrite
production in vitro instead of monitoring nitrite concentration in the circulation.
Atherogenic lipoprotein, LDL, was shown to increase eNOS generation of superoxide
anion . An increase in reactive oxygen species (ROS) resulted in oxidative stress and
cellular oxidative damage . In a hypercholesterolemic condition, increased ROS in
the endothelium increases NO breakdown . Scutellarin possesses a potent
antioxidative activity and protected cells (including endothelium) from oxidative damage
. It was demonstrated as a good ROS scavenger [8,26]. Therefore, scutellarin could
protect the vasculature through its antioxidative Clomid Uk Buy activity.
In the present study, scutellarin treatment dose dependently improved
acetylcholine-induced relaxation on aortic rings. This can be explained by the
up-regulation of eNOS RNA expression and/or increase in acetylcholine-induced
nitrate/nitrite production, which represented an increase in NO availability. Scutellarin
was shown to increase eNOS expression in a rat model of cerebral ischemia/reperfusion
. However, whether the vasoprotective effect is due to the up-regulation of eNOS
gene, the antioxidative activity Taking Clomid To Get Pregnant of scutellarin or both is presently unclear and awaits
further investigation. In the HCD group, eNOS RNA expression was down-regulated in
isolated aorta. However, several studies have shown that cardiovascular risk Buy Clomid Online Cheap factors,
including hypercholesterolemia are associated with an increase rather than a decrease in
eNOS expression [27,28]. The reason for a decrease in NO availability is more likely Buy Clomid On Line
related to eNOS dysfunction (eNOS uncoupling), which in many cases is resulted from a
reduced availability of tetrahydrobiopterin, an essential co-factor for NOS . eNOS
uncoupling will lead to superoxide and H2O2 production . The discrepancy in eNOS
RNA expression warrants further study.
In conclusion, the current results indicate for the first time that scutellarin possess
prominent hypocholesterolemic and atheroscleroprotective effects. The effects may be
brought about by scutellarin on the gene expression of eNOS in endothelial cells,
antioxidative activity or both. Confirmatory studies in other models would provide more
evidence of scutellarin's effects.
The authors greatly acknowledge Ms. Siu-Hung Tsui for providing critical comments 150 Mg Clomid and
Dr. Susan Ho for proofreading the manuscript. This work was supported by a Online Pharmacy Clomid grant from
the ?Shenzhen Virtual University Park?, Shenzhen Government and the Niche Area
Research Grant from the Hong Kong Polytechnic University.
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