ELECTROPHYSIOLOGICAL EFFECTS OF TETRAHYDROPALMATINE ON CANINE PURKINJE FIBER AND VENTRICULAR MUSCLE IN VITRO

The cellular electrophysiologic properties of a new antiarrkythmic substance,tetrahydropalmatine(TRP),were studied in isolated canine cardiac Purldnje fibers and ventricular muscles.In lharkinjc fibers,the shortening of APD50 produced by THP was concentration dependent,APD90was shortened only at higher concentrations of THP,APA and Vmax were decreased by increasing theTHP concentration to 100 and 300 μmol/L. In Veutricular muscles,THP,at higher Concentration,shortened APDs,and APD90 The reductions of Vmax and APA were significant only at highest concentration,300 μmol/L,ERP was relatively prolonged in both Purldnje fibers and ventricular muscles.These studies suggest that THP may inhibit Ca2+ and Na+ movement across the membrane of myocardlal cells.

Network Pharmacology and Experimental Validation to Explore Mechanism of Tetrahydropalmatine on Acute Myocardial Ischemia

Objective:To explore the potential molecular mechanism of tetrahydropalmatine(THP)on acute myocardial ischemia(AMI).Methods:First,the target genes of THP and AMI were collected from SymMap Database,Traditional Chinese Medicine Database and Analysis Platform,and Swiss Target Prediction,respectively.Then,the overlapping target genes between THP and AMI were evaluated for Grene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and protein-protein interaction network analysis.The binding affinity between the protein and THP was assessed by molecular docking.Finally,the protective effects of THP on AMI model and oxygen and glucose deprivation(OGD)model of H9C2 cardiomyocyte were explored and the expression levels of target genes were detected by RT-qP CR in vivo and in vitro.Results:MMP9,PPARG,PTGS2,SLC6A4,ESR1,JAK2,GSK3B,NOS2 and AR were recognized as hub genes.The KEGG enrichment analysis results revealed that the potential target genes of THP were involved in the regulation of PPAR and hormone pathways.THP improved the cardiac function,as well as alleviated myocardial cell damage.Furthermore,THP significantly decreased the RNA expression levels of MMP9,PTGS2,SLC6A4,GSK3B and ESR1(P<0.05,P<0.01)after AMI.In vitro,THP significantly increased H9C2 cardiomyocyte viability(P<0.05,P<0.01)and inhibited the RNA expression levels of PPARG,ESR1 and AR(P<0.05,P<0.01)in OGD model.Conclusions:THP could improve cardiac function and alleviate myocardial injury in AMI.The underlying mechanism may be inhibition of inflammation,the improvement of energy metabolism and the regulation of hormones.

Tetrahydropalmatine protects against methamphetamine-induced spatial learning and memory impairment in mice

Objective The purpose of this study was to investigate the effect of methamphetamine （MA） on spatial learning and memory and the role of tetrahydropalmatine （THP） in MA-induced changes in these phenomena in mice. Methods Male C57BL/6 mice were randomly divided into eight groups, according to different doses of MA, different doses of THP, treatment with both MA and THP, and saline controls. Spatial learning and memory were assessed using the Morris water maze. Western blot was used to detect the expression of extracellular signal-regulated protein kinase （ERK） in the mouse prefrontal cortex （PFC） and hippocampus. Results Repeated MA treatment significantly increased the escape latency in the learning phase and decreased the number of platform site crossings in the memory-test phase. ERK1/2 expression was decreased in the PFC but not in the hippocampus of the MA-treated mice. Repeated THP treatment alone did not affect the escape latency, the number of platform site crossings or the total ERK1/2 expression in the brain. Statistically significantly shorter escape latencies and more platform site crossings occurred in MA＋THP-treated mice than in MA-treated mice. Conclusion Repeated MA administration impairs spatial learning and memory in mice, and its co-administration with THP prevents this impairment, which is probably attributable to changed ERK1/2 expression in the PFC. This study contributes to uncovering the mechanism underlying MA abuse, and to exploring potential therapies.