RESUMEN
The PK-PD correlation models by using pharmacodynamics and pharmacokinetics were applied to study the material basis of Naomaitong,a clinical empirical prescription for the treatment of cerebral apoplexy,in inhibiting the death of PC12 nerve cells induced by Na_2S_2O_4 and Glu. In this experiment,PC12 cell death models induced by Na_2S_2O_4 and Glu were established respectively.With LDH lateral leakage and NO content as pharmacodynamic indexes,PK-PD model was established by SVM algorithm to evaluate the effective components of Naomaitong in inhibiting neural cell death. The results showed that the positive correlation of emodin methyl ether-8-O-β-D-glucopyranoside,aloe emodin,chrysophanol,rhein,emodin,ginsenoside Rg1,ginsenoside Rc,3'-methoxypuerarin and ligustilide was significant,obviously improving the LDH release and NO content. The results indicated that the contribution of Radix Puerariae Lobatae Radix and Rhei Radix et Rhizoma in Naomaitong could protect the nerve cell death induced by Na_2S_2O_4 and Glu respectively. PK-PD model was used to screen the neuroprotective components in Naomaitong,revealing the possible pharmacodynamic material basis of Naomaitong in the treatment of cerebral ischemia injury.
Asunto(s)
Animales , Ratas , Medicamentos Herbarios Chinos , Farmacología , Neuronas , Biología Celular , Fármacos Neuroprotectores , Farmacología , Células PC12RESUMEN
This research aims to develop an UHPLC method, based on core-shell column(i.e. superficially porous particles), for simultaneous determination of eight isoflavonoids including formononetin,(6αR,11αR)-3-hydroxy-9,10-dimethoxypterocarpan, calycosin-7-O-β-D-glucopyranoside,(3R)-7,2-dihydroxy-3,4-dimethoxyisoflavone, calycosin, ononin,(6αR,11αR)-9,10-dimethoxypterocarpan-3-O-β-D-glucopyranoside, and(3R)-7,2-dihydroxy-3,4-dimethoxyisoflavan-7-O-β-D-glucopyranoside in Astragali Radix. The analysis was performed on an Agilent Poroshell EC-C_(18 )column(2.1 mm×100 mm, 2.7 μm) with 0.2% formic acid solution(A)-acetonitrile(B) as mobile phase for gradient elution. The flow rate was 0.5 mL·min~(-1), with column temperature of 40 ℃ and the wavelengths were set at 260 and 280 nm. According to the results, all calibration curves showed good linearity(R~2>0.999 8) within the tested concentration ranges. Both the intra-and inter-day precisions for 8 isoflavonoids were less than 0.80%, with the mean recovery at the range of 94.71%-104.6%. Thus, the newly developed UHPLC method using core-shell column owned the advantages in terms of rapid analysis, low column pressure and less solvent consumption, thus enabling the usage of conventional HPLC systems. Meanwhile, quantitative evaluation was carried out for 22 batches of commercial Astragali Radix. It has been found that great variations occurred for the content of the individual isoflavonoids among different batches; in contrast, the total content of total 8 isoflavonoids(>0.1%) was stable in most samples, indicating that it was reasonable to involve all isoflavonoids as the chemical markers for the quality control of Astragali Radix.