Study on the mechanism and active components of Radix et Rhizoma Rhei in the treatment of Alzheimer's disease based on molecular docking

Objective:To explore the mechanism and active components of Radix et Rhizoma Rhei in the treatment of Alzheimer's disease(AD)based on molecular docking.Methods:22 major components of Radix et Rhizoma Rhei were screened from TCMSP and related literatures,which docked with the key targets of NLRP3/Caspase-1/GSDMD signaling pathway.NLRP3,Caspase-1,GSDMD inhibitors MCC950,ML132 and LDC7559 were used as positive control to analyze the docking results.Results:The docking results showed that the main components of Radix et Rhizoma Rhei had different degrees of binding with NLRP3,Caspase-1 and GSDMD targets,and the potential active components were mutanochrome and physciondiglucoside.Conclusion:Molecular docking predicts that the main components of Radix et Rhizoma Rhei may act on NLRP3/Caspase-1/GSDMD signaling pathway,and the active components may be mutanochrome and physciondiglucoside,which provides theoretical basis for revealing the anti-inflammatory mechanism and active components of Radix et Rhizoma Rhei in the treatment of AD.

Effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric kidney transplantation:a systematic review and meta-analysis of observational studies

Background:CYP3A5 genetic polymorphisms have been reported to be strongly associated with the tacrolimus pharmacokinetics in adult kidney transplantation.However,there is no published meta-analysis in the influence of CYP3A5 variants on the requirements of the tacrolimus dose in pediatric renal-transplant recipients (RTRs).We wished to determine the effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric RTRs.Methods:A literature search was conducted to include relevant articles by searching PubMed,EMBASE and the Cochrane Central Register of Controlled Trials.Pharmacokinetic-associated parameters such as dose administration,as well as concentrations and dose-adjusted concentrations of tacrolimus were extracted and the metaanalysis undertaken.Results:The meta-analysis involved four studies and one study series involving 268 pediatric RTRs.A significant difference was observed in the mean trough concentration/ dose of tacrolimus between recipients carrying CYP3A5* 3/*3 variants (referred to as 'non-expressers') and those carrying CYP3A5*1 (referred to as 'expressers') [standard mean difference (SMD)=-1.09,95% confidence interval (CI):-1.92 to-0.25,P=0.011].Moreover,significance was observed in the mean daily dose of tacrolimus between nonexpressers and expressers in pediatric RTRs (SMD=0.44,95% CI:0.20 to 0.68,P<0.001).Conclusion:Our meta-analysis identified a positive correlation between CYP3A5 genotypes and tacrolimus pharmacokinetics in pediatric RTRs.