Serum nitric oxide synthase activity is a novel predictor of impaired vasorelaxation in rats.

1. It is well documented that both acetylcholine (ACh)-evoked arterial relaxation and brachial artery flow-mediated vasodilatation are blunted in hypercholesterolaemic patients. However, there are no simple diagnostic methods to detect the pathology of blood vessels of patients. 2. To establish the use of serum nitric oxide synthase (NOS) activity as a diagnostic parameter for impaired vasorelaxation, animals with different levels of vascular healthiness were made by feeding Sprague-Dawley rats a normal diet, a high-cholesterol diet (HCD) or an HCD supplemented with 10 mg/kg per day, p.o., simvastatin, a cholesterol-lowering drug, for 30 days. Serum total cholesterol levels, serum NOS activity and ACh-induced vasorelaxation of the isolated aorta were determined at the end of the experiment. 3. Consumption of HCD for 30 days resulted in an increase in serum total cholesterol, attenuated ACh-induced nitric oxide/endothelium-dependent aortic relaxation and decreased NOS activity. Concomitant administration of simvastatin lowered the elevated blood cholesterol levels with complete reversal of the attenuated ACh-induced aortic relaxation and serum NOS activity. An attempt was made to correlate serum NOS activity and the magnitude of ACh-elicited vascular relaxation among the different groups. A positive correlation (r = 0.8329; P < 0.001; n = 30) was found between serum NOS activity and vascular relaxation. 4. This finding is a good foundation for the development of a simple and low-cost alternative for diagnosing vascular diseases and evaluating the effectiveness of drugs on the vascular system in patients.

Enhancement of in vitro and in vivo anticancer activities of polysaccharide peptide from Grifola frondosa by chemical modifications.

CONTEXT: Grifola frondosa (Polyporaceae), maitake, is a widely consumed edible mushroom in some Asian countries. The fruit bodies and mycelia of maitake have shown different bioactive compounds with anticancer and other therapeutic properties. OBJECTIVE: This study evaluated three chemically modified maitake polysaccharide-peptides' (MPSP) adjuvant effect (in vivo) and anticancer activity (in vitro growth inhibitory effect) compared with crude MPSP from G. frondosa. MATERIALS AND METHODS: We investigated the possibility of enhancing the adjuvant effect and anticancer effect of crude MPSP by using simple chemical modification methods to convert crude MPSP to phosphorylated, acetylated or esterified MPSPs. The adjuvant effect and growth inhibitory effect were evaluated by C6 cell inoculated rat model with cyclophosphamide (CPA) treatment and in vitro cell viability assay, respectively. RESULTS: All four tested MPSPs showed significant adjuvant effect to CPA treatment on rats inoculated with C6 cancer cells. In addition, an obvious growth inhibitory effect was observed in C6 cancer cells but not in normal brain cells treated with various forms of MPSPs. Only phosphorylation could significantly (p < 0.05) improve the adjuvant effect (in vivo) and growth inhibitory effect. A same rank order (phosphorylated MPSP > esterified MPSP ≥ acetylated MPSP ≥ crude MPSP) of efficacy was observed in both the in vivo and in vitro assays. DISCUSSION AND CONCLUSION: This study showed chemical phosphorylation could markedly enhance both adjuvant effects and growth inhibitory effects. This study demonstrated the feasibility of enhancing the efficacy of MPSP by using a simple chemical modification method, and this provides a foundation for future study in this area.