ABSTRACT
Objective:To study on the correlation between integrated pharmacokinetics and pharmacodynamic effects of five active components(oxidized paeoniflorin,paeoniflorin,quercetin,gallic acid, paeonol) in Moutan Cortex. Method:Rats were divided into blank group,model group(syndrome of blood-heat and blood stasis) and drug-administered group.The concentration of five active components in serum were detected with UPLC-MS at different time points after being administrated ethanol extract of Moutan Cortex.The integrated concentrations were calculated according to area under the curve(AUC) self-defined weighting coefficiency.At the same time,the enzyme-linked immunosorbent assay(ELISA) was used to determine the contents of thromboxane B2(TXB2) and 6-keto-prostaglandin F1α(6-keto-PGF1α) in serum at different time points,and then correlation between pharmacodynamics and integrated pharmacokinetics of these five active ingredients was analyzed. Result:At different time points(0.083,0.25,0.5,0.75,1,2,3,4,6,8,10,12 h),the integrated plasma concentrations of these five active ingredients in Moutan Cortex(158.65,174.60,220.13,227.23,244.31,251.51,404.28,654.39,472.62,355.04, 231.56,199.40 mg·L-1) had a good correlation with concentration of TXB2(264.44,261.03,284.93,273.30,264.04, 278.90,274.83,303.58,260.03,264.78,264.40,256.62 μg·L-1) and value of TXB2/6-keto-PGFlα(4.50,4.47,3.66,3.37, 3.29,3.66,3.71,4.30,3.63,3.65,3.75,3.66). Conclusion:There is a good correlation between the dynamic changes in vivo of active components from Moutan Cortex and pharmacodynamic effects of activating blood circulation of this herb.
ABSTRACT
OBJECTIVE:To develop the determination method for plasma concentration of effective components in essential oil from Curcuma phaeocaulis,and to study its integrated pharmacokinetics. METHODS:Sixteen rats were given the extract of essential oil from C. phaeocaulis 1.0 g/kg(by crude drug)intragastrically;blood samples 300-400 μL from orbit were collected 0, 0.17,0.5,1,2,2.5,3,4,6,8,10,12,24 h after medication. The plasma concentration of α-pinene,1,8-cineole,borneol, β-elemene,curcumol,germacrone and curdione in rats were determined by GC-MS. The determination was performed on DB-5 capillary column,using helium as carrier gas,at the flow rate of 1.2 mL/min. The injector temperature was 270 ℃,by temperature programming,and split ratio was 20∶1. The sample size was 1 μ L. The ion source was electrospray ion source. The selective reaction monitoring mode was used for the positive ion scanning in the range of m/z 20-500. Pharmacokinetic parameters of above effective components were calculated by using DAS 2.0 software. The weight coefficients were customized according to the proportion of AUC0-∞in the sum of AUC0-∞. The integrated pharmacokinetic parameters of multiple effective components in essential oil from C. phaeocaulis were calculated. RESULTS:The linear range of α-pinene,1,8-cineole,borneol,β-elemene, curcumol, germacrone, and curdione were 2.71-173.54, 7.76-496.88, 3.37-215.72, 21.68-1 387.50, 40.21-2 573.44, 24.84-3 179.69,47.78-3 057.81 ng/mL,respectively (r＞0.99). The lower limits of quantitation were 2.71,7.76, 3.37,21.68,40.21,24.84,47.78 ng/mL,respectively. The precision,accuracy and matrix effects were in line with related requirements of quantitative analysis of biological samples. The pharmacokinetic parameters of α-pinene,1,8-cineole,borneol, β-elemene,curcumol,germacrone,and curdione were as follows that cmaxwere (34.72 ± 9.97),(99.86 ± 5.54),(16.10 ± 3.37), (248.98±86.19),(673.75±104.15),(2 353.64±637.83),(2 420.04±708.51)ng/mL;tmaxwere(2.33±0.29),(0.67±0.29), (1.33±0.58),(1.83±0.76),(0.83±0.29),(0.89±0.18),(1.17±0.76)h;t1/2were(8.64±1.46),(8.98±1.63),(12.43± 2.88),(19.86 ± 4.05),(15.63 ± 5.50),(14.17 ± 4.13),(7.14 ± 0.67)h;AUC0-twere (189.78 ± 89.10),(454.74 ± 82.43), (100.55±8.27),(1 067.37±216.55),(3 154.16±405.94),(16 501.24±663.88),(12 524.92±3 222.10)ng·h/mL;AUC0-∞were(229.57±93.50),(524.32±81.67),(146.28±10.74),(2 092.70±416.18),(5 388.65±661.86),(28 198.87±4 102.62), (14 139.35 ± 3 109.19)ng·h/mL,respectively. After integration,the pharmacokinetic parameters were as follows that cmaxwas 1 880.94 ng/mL; tmaxwas 0.50 h; t1/2was 11.22 h;AUC0-twas 13 050.89 ng·h/mL;AUC0- ∞was 19 015.21 ng·h/mL. CONCLUSIONS: The method can be used for the detection of plasma concentration of effective components in rats;pharmacokinetic parameters of essential oil from C. phaeocaulis after integration are greatly different from single effective component,which can provide reference for characterization of its overall pharmacokinetics.