Scutellarin is the main effective constituent of breviscapine, a flavonoid mixture isolated from the dried whole plant of Erigeron breviscapus (Vant.) Hand-Mazz, and valsartan is used as an antihypertensive drug. These two drugs have already been clinically used together to treat diabetic nephropathy (DN) in China, and the combined medications showed some enhanced protection against DN. The aim of this study is to investigate the potential pharmacokinetic interaction between scutellarin and valsartan in rats. Breviscapine injection (20 mg x kg(-1), i.v.) and valsartan (15 mg x kg-, i.g.), either alone or together were given to 18 male Sprague-Dawley rats. Concentrations of scutellarin and valsartan were quantified by HPLC, and pharmacokinetic parameters were calculated by non-compartmental methods. We found that the pharmacokinetic parameters of scutellarin altered significantly after co-administration of oral valsartan. The plasma clearance (CL(p)) and the bile clearance (CL(b)) of scutellarin were reduced significantly in the presence of valsartan. After oral administration of valsartan with or without intravenous scutellarin, however, the pharmacokinetic parameters of valsartan were comparable. In conclusion, our data suggests that the concurrent use of valsartan reduces the biliary excretion of scutellarin, and this may be due to the inhibitory effect of valsartan on the biliary excretion of scutellarin mediated by Mrp2 (Multidrug resistance-associated protein 2).

OBJECTIVE:To promote rational use of traditional Chinese medicines. METHODS:The practical importance of applying basic pharmacoeconomic theory to the rational use of traditional Chinese medicines was analyzed and the measures regarding how to apply the pharmacoeconomic theory to guide rational use of traditional Chinese medicines were put forward. RESULT & CONCLUSION: It is quite necessary and practical to apply the basic pharmacoeconomic theory to the rational use of traditional Chinese medicine, which plays a positive role in promoting rational use of traditional Chinese medicines.

OBJECTIVE:To study the pharmacokinetics effects of naloxone combination on Shenmai injection in rats in vivo. METHODS:12 rats were randomly divided into monotherapy group (Shenmai injection 9.00 ml/kg,iv) and combination group (Shenmai injection 9.00 ml/kg+naloxone 1.80 ml/kg,iv). The blood samples were collected before administration and 0.083,0.25, 0.5,0.75,1,1.5,2,3,6,12,24,48,96 and 144 h after administration. HPLC was adopted to determine the plasma concentra-tions of ginsenosides Rg1,Re and Rb1,and DAS 2.0 software was used to calculate the pharmacokinetic parameters. RESULTS:Compared with monotherapy group,the plasma concentration of ginsenosides Rg1 in combination group was increased,CL was de-creased,t1/2 and MRT were prolonged,and AUC0-144 h was increased;the plasma concentration of ginsenosides Re was increased,Ke was decreased,t1/2 was prolonged,MRT was shortened,and AUC0-144 h was increased;the plasma concentration of ginsenosides Rb1 was decreased,Ke was increased,t1/2 and MRT were shortened,and AUC0-144 h was decreased,with significant differences(P<0.01 or P<0.05). CONCLUSIONS:Shenmai injection combined with naloxone can slow down the removing of ginsenosides Rg1 and Re in vivo,and obviously the plasma concentration of Shenmai injection is higher than monotherapy group;speed up the removing of ginsenosides Rb1,and the plasma concentration of Shenmai injection is lower than monotherapy group obviously.

Various omics and their combined techniques have certain applications in the study of the mechanism of toxicity of Chinese materia medica, the screening of toxic biomarkers, and the prediction of the toxicity of Chinese materia medica. It has been found that the current application scope of exploring the toxicity of Chinese materia medica based on omics technology still needs to be expanded. In terms of organ damage caused by Chinese materia medica, omics technology is mostly used to study hepatotoxicity. In terms of the attenuation mechanism of TCM, proteomics and metabolomics have more advantages, and the two have potential prospects in exploring the processing or compatibility of TCM to reduce toxicity and increase efficiency. The combination of omics technology with network pharmacology, bioinformatics and other technologies is more conducive to providing references for the in-depth study of the toxicity of Chinese materia medica.

OBJECTIVE To explore the lipid-regulating mechanism of the classic prescription Zexie Decoction on hyperlipidemia model mice.METHODS ELISA method was used to detect the four blood lipid indexes,liver function indicators and cholesterol acyltransferase levels in serum.HE and Oil Red O staining were used to determine the pathology of liver tissue.Network pharmacology was used to predict the lipid-lowering related targets of Zexie Decoction,and the GO function and KEGG pathway enrichment analyses of the intersection targets were realized.PCR chip technology was used to detect the target genes for network pharmacology screening,and qPCR and Western blot were used to detect gene and protein expression levels.RESULTS Zexie Decoction significantly regula-ted the four blood lipid indexes in hyperlipidemia model mice,improved the increase in liver damage indicators caused by high lipids,and had a reverse regulatory effect on the key enzymes HMGR and CYP7A1 of lipid metabolism and the lipid transporters ABCA1 and Apo-A1 in liver tissue.HE and Oil Red O staining showed that Zexie Decoction improved the pathological morphology of liver tissue,reduced lipid deposition in liver tissue,and significantly decreased the positive area ratio(P<0.01).The PCR chip obtained 44 re-verse-regulated genes,GO functional enrichment analysis obtained 266 entries,and KEGG pathway enrichment analysis screened 99 signaling pathways.The results of qPCR and Western blot showed that Zexie Decoction significantly downregulated the expression of PIK3CG,AKT1,and IL-6 genes(P<0.05,P<0.01),upregulated the expression of ABCG1 gene(P<0.05),downregulated PI3Kinase p110β,p-AKT(Ser473)and SREBP-1c protein expression levels(P<0.01),and reversely regulated miR21-5p(P<0.01).CONCLUSION Zexie Decoction has a significant regulatory effect on lipid metabolism in hyperlipidemia model mice and can improve liver damage caused by hyperlipidemia.Its lipid-regulating effect may be related to regulating cholesterol metabolism and transport in the body,and is closely linked to the miR21/PI3K-Akt/SREBP pathway.The lipid-regulating effect of the whole formula of Zexie Decoction is better than that of a single herb.