ABSTRACT
OBJECTIVE：To study the pr otective effect of schisandrin A （SA）on CCl 4-induced liver fibrosis model mice and its mechanism. METHODS ：Mice were randomly divided into blank control group ，model group ，silymarin group （positive control，100 mg/kg），SA low-dose and high-dose groups （20，40 mg/kg），with 10 mice in each group. Except for blank control group，other groups were given CCl 4 subcutaneously to induce liver fibrosis model. After successful modeling ，administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 6 weeks；blank control group and model group were given constant volume of 0.5％sodium carboxymethyl cellulose solution intragastrically by the same way. HE staining was used to observe the pathological changes of liver tissue in mice. UV spectrophotometry and ELISA assay were adopted to detect the serum levels of liver injury indexes （ALT and AST ）and the contents of inflammatory factors （TNF-α，IL-1β，IL-6）. Western blotting assay was used to detect the expression of NOD like receptor protein 3（NLRP3）/NF-κB and TGF-β/Smad signaling pathway protein. RESULTS ：Compared with blank control group ，obvious pathological changes of liver fibrosis were observed in model group. The serum levels of liver injury indexes and contents of inflammatory factors were significantly increased （P＜0.01）. The expression of NLRP 3，apoptosis associated spot-like protein ，Caspase-1 and IL- 1β，TGF-β1 and ratios ofp-NF-κB p65/NF-κB p65，p-IκBα/IκBα，p-Samd3/Smad3 were increased significantly （P＜0.01）. Compared with model group ，SA could significantly relieve hepatic fibrosis in mice ，reduce serum levels of liver injury indexes and contents of inflammatory factors ，as well as the expression of NLRP 3/NF-κB and TGF-β/Smad signaling pathway protein and phosphorylation level（P＜0.01）. CONCLUSIONS ： SA can effectively relieve liver injury and inflammation of CCl 4-induced hepatic fibrosis model mice ，which may be through the regulation of NLRP 3/NF-κB and TGF-β/Smad3 signaling pathways ，thus inhibiting the process of liver fibrosis.
ABSTRACT
The aim of the research was to investigate the pharmacokinetics (PK) of enteric-coated mycophenolate sodium (EC-MPS) by quantification of the active metabolite of mycophenolic acid (MPA) after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from 0 to 12 h after EC-MPS administration. MPA plasma concentrations were measured by UPLC-UV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to 900 mg,and AUCdid not increase with dose escalation. The AUC,,andfor the 540 720 and 900 mg doses were not significantly different, respectively (>0.05). AUCandwere increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC,andwere considerable. Nonlinear PK relationships were found from the doses of 540-900 mg of EC-MPS.
ABSTRACT
OBJECTIVE:To establish a method for simultaneous determination of tanshinol,caffeic acid,rosmarinic,salviano-lic acid B,salvianolic acid A,tanshinoneⅠ,cryptotanshinone,tanshinone ⅡA and ursolic acid in Compound xueshuantong cap-sules. METHODS:UPLC-MS/MS method was adopted. The determination was performed on ACQUITY UPLC? BEH C18 column with mobile phase consisted of acetonitrile-0.1%formic acid(gradient elution)at the flow rate of 0.2 mL/min. The column tempera-ture was 40 ℃,and the temperature of injector was 10 ℃. Analysis time was 7 min,and sample size was 5 μL. The electrospray ionization source(ESI)was used;ion source temperature was 150℃;capillary voltage was 3.5 kV;cone flow was 50 L/h;desol-vation temperature was 350 ℃;desolvation gas flow was 650 L/h;nebuliser pressure was 7 × 105 Pa;ion monitoring and multiple reaction monitoring (MRM) was performed. RESULTS:The linear ranges of tanshinol,caffeic acid,rosmarinic,salvianolic acid B,salvianolic acid A,tanshinoneⅠ,cryptotanshinone,tanshinone ⅡA and ursolic acid were 10.0-100.0 μg/mL (r=0.9998), 0.1-1.0 μg/mL(r=0.9998),4.0-40.0 μg/mL(r=0.9999),10.0-100.0 μg/mL(r=0.9999),15.0-150.0 μg/mL(r=0.9997), 8.0-80.0 μg/mL(r=0.9998),10.0-100.0 μg/mL(r=0.9997),50.0-500.0 μg/mL(r=0.9997)and 6.0-60.0 μg/mL(r=0.9998), respectively. The limits of quantitation were 40.0,9.6,38.0,88.0,130.0,39.0,4.4,3.2 and 10.0 ng/mL,separately. The limits of detection were 12.0,3.0,11.0,26.0,39.0,12.0,1.3,1.0 and 3.0 ng/mL,respectively. RSDs of precision,stability and repro-ducibility tests were all lower than 3%. The recoveries were 97.34%-103.20%(RSD=2.19%,n=6),97.22%-102.39%(RSD=2.03%,n=6),98.51%-101.70%(RSD=1.32%,n=6),97.86%-102.49%(RSD=2.09%,n=6),96.75%-103.12%(RSD=2.36%,n=6),98.43%-101.65%(RSD=1.25%,n=6), 97.59%-101.50%(RSD=1.50%,n=6), 96.45%-102.88%(RSD=2.58%,n=6),97.02%-103.11%(RSD=2.38%,n=6),separately. CONCLUSIONS:The method is simple and accurate,and can be used for simultaneous determination of 9 components in Compound xueshuantong capsules.