ABSTRACT
The aim of the present study is to evaluate the vasodilation effects of Tongmai Yangxin Pills (TMYX) on rat mesenteric artery as well as its mechanism of action. The relaxation effects of TMYX extracts with different concentrations were determined on isolated rat mesenteric artery in normal condition as well as pretreating by phenylephrine and KCl. Vascular relaxation effects of TMTX were also determined in mesenteric artery preincubated with L-ANME and indomethacin or in endothelium denuded mesenteric artery. Moreover, effects of TMYX by 50 mg·L⁻¹ on NO secretion and the phosphorylation of eNOS in a cellular model of human umbilical vein endothelial cell (HUVEC) pretreated with or without L-NAME were also observed. The experimental results showed that TMYX has no obvious effect on vasodilation of arteries in normal or KCl pretreated condition, while it can dose-dependently relax the rat mesenteric artery with intact endothelium stimulated with phenylephrine at a maximal diastolic rate of (64.71±10.03)%. After preincubating with L-NAME for 15 min or removal of mesenteric artery endothelium, the maximal diastolic rate was decreased to (35.77±8.93)% and (25.85±10.84)% respectively. However, preincubating with indomethacin had no inhibitory effect on TMYX induced vascular relaxation. Meanwhile, TMYX at 50 mg·L⁻¹ could increase the expression of P-eNOS and the secretion of NO in HUVEC. L-NAME significantly inhibited NO release and phosphorylation of eNOS induced by TMYX. The results suggested TMYX exerted endothelium-dependent relaxation effects against PE-induced contractions of isolated rat mesenteric artery through NO-cGMP signaling pathway.
Subject(s)
Animals , Humans , Rats , Endothelium, Vascular , Mesenteric Arteries , VasodilationABSTRACT
To conduct multiple-reaction monitoring(MRM) quantitative analysis with high-performance liquid chromatography coupled with mass spectrometry method, establish the quantification method of magnolol and honokiol in blood sample under negative ion mode with ibuprofen as internal standard, investigate the pharmacokinetic process of lignans constituents after oral administration of Weichang'an pill(WCA) at different doses, and provide theoretical basis to further reveal the material basis of WCA's anti-diarrhea effect. In the plasma samples, the linear relationship was good over the concentration range of 5.25 to 1 344.00 μg•L ⁻¹ for magnolol and 10.08 to 2 580.00 μg•L ⁻¹ for honokiol. The results of precision, stability, and extraction recovery tests showed that the determination method of plasma concentration for such compositions was stable and reliable. Dose-dependence was shown for magnolol and honokiol in the plasma concentration-time profile. The results indicated that the time to reach the maximum plasma concentration(Tmax) for lignanoids was 0.55-1.42 h, when the maximum plasma concentration(Cmax) could reach 996.36-2 330.96,189.87-1 469.43 μg•L ⁻¹ respectively for magnolol and honokiol. The lignanoids could be absorbed rapidly in the blood after oral administration of WAC pills, providing experimental basis to prove rapid and long-acting anti-diarrhea effect of WAC pills after oral administration.
ABSTRACT
A HPLC-MS/MS multiple-reaction monitoring (MRM) quantitative analysis was made to establish a determination method for drug concentrations of costunolide (Co) and dehydrocostuslactone (De) in blood samples in the positive ion mode, with diazepam as the internal standard substance, in order to study the pharmacokinetic process of sesquiterpene lactones costunolide and dehydrocostuslactone after the oral administration of Weichang'an pills, and provide an theoretical basis for further studies on the substance basis for the anti-diarrhea effect of Weichang'an pills. In the blood samples, Co and De showed a good linearity within concentration ranges 0.700 0-769.7, 2.510-956.0 μg x L(-1), respectively. The results of precision, stability and recovery experiences proved the stability and reliability of the plasma concentration determination method. After the oral administration, the concentrations of Co and De in plasma increased with the increase in dose, with T(max) between 10.65-12.98 h, indicating a long time to reach peak plasma concentrations; C(max) of costunolide and dehydrocostuslactone ranged between 3.750-5.450,15.34-44.52 μg x L(-1), respectively. The in vivo adsorption of Co and De conformed to the one-compartment model, with a longer time to attain the peak plasma concentrations. These results provided an experimental basis for revealing the active substance basis and clinical medication of Weichang'an pills.