ABSTRACT
Bridelia ferruginea Benth. (Fam. 'Euphorbiaceae) is known to possess potent anti-inflammatory activity. Here, we investigated its vasomodulatory effect, as anti-inflammatory therapy that beneficially impact the cardiovascular system. Extracts (Bf1, Bf-HA) and fraction (Bf2) of B. ferruginea (Bf), were prepared from the bark of Bf to study their vasomodulatory effect using rat aortic rings. The vasorelaxant effect of Bf1 and Bf2 was mediated by the activation of nitric oxide synthase/endothelial isoform (NOS3) as confirmed by EA.hy926 endothelial cells, real-time PCR and Western blotting. Mass spectral analysis of these extracts and fraction was performed to understand the profile of compounds present in them. Mass spectral analysis showed the presence of similar ions in both Bf1 and Bf2 while Bf-HA showed different patterns. Vasorelaxant effect of Bf1 and Bf2 in phenylephrine (PE) pre-contracted endothelium intact aortic rings was blocked significantly in the presence of both N-nitro-L-arginine methyl ester (L-NAME) or soluble guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one [ODQ]). However, cyclo-oxygenase (COX) inhibitor (indomethacin) did not exert any change. In contrast, Bf-HA significantly inhibited ACh-induced vasorelaxation, but had no effect on sodium nitroprusside (SNP)-mediated relaxation, thereby suggesting NOS inhibitory activity in the extract. Studies with Bf1 and Bf2 on EA.hy926 cells demonstrated NOS3 mediated nitric oxide (NO) generation. Purified fractions of Bf, thus possess vasorelaxant compounds, which remain to be identified.
ABSTRACT
Background & objectives: Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Methods: Male Golden Syrian hamsters on high fructose diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. Results: Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1)α and PGC-1β genes known to be involved in lipid and glucose metabolism. Interpretation & conclusions: High fructose feeding to rats and hamsters led to the development of insulin resistance, hyperglycaemia, endothelial dysfunction and oxidative stress. C. oil prevented development of thrombotic complications associated with insulin resistance perhaps by modulating genes involved in lipid and glucose metabolism. Further studies are required to confirm these findings.
ABSTRACT
Recently reports of a variable platelet response to aspirin and potential resistance to therapy have emerged with thienopyridines group of drugs. However the data available on clopidogrel resistance is scarce. The present study was initiated to prospectively evaluate the prevalence of clopidogrel resistance in patients of acute coronary syndrome(ACS) presently on dual anti platelet therapy by using an established method of optical platelet aggregation. We studied 39 patients of ACS, who were on clopidogrel 300 mg bolus followed by 75 mg per day for 3 days along with aspirin 325 mg per day. Fasting blood samples were assessed using optical platelet aggregation (Chronolog Corp, USA). Clopidogrel resistance was defined as <10% decrease from baseline in platelet aggregation. Clopidogrel semi-responders were defined as 10-29% ( <30%) decrease from baseline in platelet aggregation. Clopidogrel non-responders were defined as a composite of resistant and semi-responders. A baseline mean platelet aggregation obtained from 18 healthy subjects was 63.8 +/- 14.75% with 5 mu and 68.8 +/-13.91% with 10 mu of Adenosine Diphosphate. Hence, the definition of clopidogrel resistance was set as aggregation of >57% with 5 mu ADP and >61.9% with 10 mu ADP (< 10% decrease from baseline). The definition of clopidogrel semi-responder was set as aggregation of >or=45% with 5 mu ADP and >or=48% with 10 mu ADP (10-29% decrease from baseline). The mean platelet aggregation with 5 mu and 10 mu of Adenosine Diphosphate in the patient group was 30.77 +/- 17.19% and 35.71 +/- 17.0% respectively. Based on these criteria, 2.54% patients were found to be clopidogrel resistant, 12.7% were clopidogrel semi-responders and 84.7% were clopidogrel responders. On comparison of clopidogrel responders with non-responders, females ( p=0.07) and patients with higher serum triglyceride levels (p=0.08), had a trend to be more inclined towards clopidogrel non-responders. All other parameters tested namely age, smoking, diabetes, hypertension, obesity, cholesterol, hemoglobin, platelet count, ejection fraction and concurrent drug intake did not show any statistically significant difference among the groups. CONCLUSIONS: This study shows that clopidogrel resistant and clopidogrel semi-responders do occur in Indian patients with ACS and there are no reliable clinical predictors for this condition. The diagnosis therefore relies primarily on laboratory tests.