Objective:To explore the synergic mechanism of ginsenoside Rg,(Rg,)and aconitine(AC)by acting on normal neonatal rat cardiomyocytes(NRCMs)and pentobarbital sodium(PS)-induced damaged NRCMs.Methods:The toxic,non-toxic,and effective doses of AC and the most suitable compatibility concentration of Rg,for both normal and damaged NRCMs exposed for 1 h were filtered out by 3-(4,5)-dimethytthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide,respectively.Then,normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg,for 1 h,and the cellular activity,cellular ultrastructure,apoptosis,leakage of acid phosphatase(ACP)and lactate dehydrogenase(LDH),intracellular sodium ions[Na+],potassium ions[K+]and calcium ions[Ca2+]levels,and Nav1.5,Kv4.2,and RyR2 genes expressions in each group were examined.Results:For normal NRCMs,3000 μmol/L AC significantly inhibited cell viability(P＜0.01),promoted cell apoptosis,and damaged cell structures(P＜0.05),while other doses of AC lower than 3000 μ mol/L and the combinations of AC and Rg,had little toxicity on NRCMs.Compared with AC acting on NRCMs alone,the co-treatment of 3000 and 10 μ mol/L AC with 1 μ mol/L Rg,significantly decreased the level of intracellular Ca2+(P＜0.01 or P＜0.05),and the co-treatment of 3000 μ mol/L AC with 1 μ mol/L Rg,significantly decreased the level of intracellular Ca2+via regulating Nav1.5,RyR2 expression(P＜0.01).For damaged NRCMs,1500 μ mol/L AC aggravated cell damage(P＜0.01),and 0.1 and 0.001 μ mol/L AC showed moderate protective effect.Compared with AC used alone,the co-treatment of Rg,with AC reduced the cell damage,0.1 μ mol/L AC with 1 μ mol/L Rg,significantly inhibited the level of intracellular Na+(P＜0.05),1500 μ mol/L AC with 1 μ mol/L Rg,significantly inhibited the level of intracellular K+(P＜0.01)via regulating Nav1.5,Kv4.2,RyR2 expressions in impaired NRCMs.Conclusion:Rg,inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of[Na+],[K+],and[Ca2+].

XU Xin;XIE Xiao-fang;DONG Yan-hong;ZHANG Hui-qiong;PENG Cheng

State Key Laboratory of Southwestern Chinese Medicine Resources,Pharmacy School of Chengdu University of Traditional Chinese Medicine,Chengdu(611137),China;Department of Pharmacy,Sichuan Veterans'Hospital,Chengdu(611236),China

中国结合医学杂志（英文版）

[1]XU Xin;XIE Xiao-fang;DONG Yan-hong;ZHANG Hui-qiong;PENG Cheng-.Ginsenoside Rg1 Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro)[J].中国结合医学杂志（英文版）,2022(08):693-701

Reduces,Cardiotonic,Aconitine,aconitine,pentobarbital,dimethytthiahiazo,Ca2+via,cardiotonic

Ginsenoside,Rg1,Cardiotoxicity,While,Increases,Effect,vitro,Objective,To,explore,synergic,mechanism,ginsenoside,by,acting,normal,neonatal,cardiomyocytes,NRCMs,sodium,PS,induced,damaged,Methods,effective,doses,most,suitable,compatibility,both,exposed,were,filtered,out,y1,phenytetrazoliumromide,respectively,Then,impaired,treated,chosen,concentrations,alone,activity,ultrastructure,apoptosis,leakage,acid,phosphatase,ACP,lactate,dehydrogenase,LDH,intracellular,Na+,potassium,K+,calcium,levels,Nav1,Kv4,RyR2,genes,expressions,each,group,examined,Results,For,significantly,inhibited,viability,promoted,structures,while,other,lower,than,combinations,had,little,Compared,treatment,decreased,regulating,aggravated,showed,moderate,protective,used,reduced,Conclusion,cardiotoxicity,enhanced,channels,pathway

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