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Ginsenoside Rg1 Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro

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Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To explore the synergic mechanism of ginsenoside Rg1 (Rg1) 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 Rg1 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 Rg1 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 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 Rg1 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 Rg1 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 Rg1 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 Rg1 with AC reduced the cell damage, 0.1 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular Na+ (P<0.05), 1500 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular K+ (P<0.01) via regulating Nav1.5, Kv4.2, RyR2 expressions in impaired NRCMs.

Conclusion

Rg1 inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of [Na+], [K+], and [Ca2+].

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Authors and Affiliations

  1. State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School of Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China

    Xin Xu, Xiao-fang Xie, Hui-qiong Zhang & Cheng Peng

  2. Department of Pharmacy, Sichuan Veterans’ Hospital, Chengdu, 611236, China

    Yan-hong Dong

Authors
  1. Xin Xu
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  2. Xiao-fang Xie
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  3. Yan-hong Dong
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  4. Hui-qiong Zhang
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  5. Cheng Peng
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Corresponding author

Correspondence to Cheng Peng.

Additional information

Supported by the National Natural Science Foundation of China (Nos. 81630101 and 81891012), Department of Science and Technology of Sichuan Province (No. 2018JZ0081), the Open Research Fund of Chengdu University of Traditional Chinese Medicine Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China (No. 2020XSGG001), Special Project for the Central Government to Guide the Development of Local Science and Technology in Sichuan Province (No. 20ZYKJCX0006)

Conflict of Interest

The authors have no conflicts of interest to declare.

Author Contributions

Xu X and Xie XF contributed equally to this work. Xie XF and Dong YH designed the study, Xu X analyzed the data, Xu X and Xie XF worte the paper, Peng C provided research fund support. Dong YH, Xu Xin and Zhang HQ performed the experiments.

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Xu, X., Xie, Xf., Dong, Yh. et al. Ginsenoside Rg1 Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro. Chin. J. Integr. Med. 28, 693–701 (2022). https://doi.org/10.1007/s11655-022-3509-0

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  • DOI: https://doi.org/10.1007/s11655-022-3509-0

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