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, 3000 µ mol/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 1 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 1 significantly decreased the level of intracellular Ca 2+ ( P <0.01 or P <0.05), and the co-treatment of 3000 µ mol/L AC with 1 µ mol/L Rg 1 significantly decreased the level of intracellular Ca 2+ via regulating Nav1.5, RyR 2 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 1 with AC reduced the cell damage, 0.1 µ mol/L AC with 1 µ mol/L Rg 1 significantly inhibited the level of intracellular Na + ( P <0.05), 1500 µ mol/L AC with 1 µ mol/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+ ].