Ginsenoside Rg_(1)Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro

Objective To explore the synergic mechanism of ginsenoside Rg_(1)(Rg_(1))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_(1) for both normal and damaged NRCMs exposed for 1 h were filtered out by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide,respectively.Then,normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg_(1) 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[Ca^(2+)]levels,and Nav1.5,Kv4.2,and RyR_(2) genes expressions in each group were examined.Results For normal NRCMs,3000µmol/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 3000µmol/L and the combinations of AC and Rg_(1) had little toxicity on NRCMs.Compared with AC acting on NRCMs alone,the co-treatment of 3000 and 10µmol/L AC with 1µmol/L Rg_(1) significantly decreased the level of intracellular Ca^(2+)(P<0.01 or P<0.05),and the co-treatment of 3000µmol/L AC with 1µmol/L Rg_(1) significantly decreased the level of intracellular Ca^(2+)via regulating Nav1.5,RyR_(2) expression(P<0.01).For damaged NRCMs,1500µmol/L AC aggravated cell damage(P<0.01),and 0.1 and 0.001µmol/L AC showed moderate protective effect.Compared with AC used alone,the co-treatment of Rg_(1) with AC reduced the cell damage,0.1µmol/L AC with 1µmol/L Rg_(1) significantly inhibited the level of intracellular Na+(P<0.05),1500µmol/L AC with 1µmol/L Rg_(1) significantly inhibited the level of intracellular K+(P<0.01)via regulating Nav1.5,Kv4.2,RyR_(2) expressions in impaired NRCMs.Conclusion Rg_(1) inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of[Na^(+)],[K^(+)],and[Ca^(2+)].