Ginsenoside Rg<sub>1</sub> Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine <italic style="font-style: italic">in vitro</italic>

Your Location：

Home >

Browse articles >

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

Original Article | Updated：2022-07-20

|

- Ginsenoside Rg₁ Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro
- Chinese Journal of Integrative Medicine Vol. 28, Issue 8, Pages: 693-701(2022)
- Affiliations：
  
  1.State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School of Chengdu University of Traditional Chinese Medicine, Chengdu (611137), China
  2.Department of Pharmacy, Sichuan Veterans' Hospital, Chengdu (611236), China
- Author bio：
  
  Prof. PENG Cheng, E-mail:cdtcmpengcheng@126.com
- Funds：
- DOI：10.1007/s11655-022-3509-0
  CLC：
- Published：2022-08，
  
  Published Online：20 June 2022，
  
  Accepted：06 January 2021
Scan for full text
Xin XU, Xiao-fang XIE, Yan-hong DONG, et al. Ginsenoside Rg₁ Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro. [J]. Chinese Journal of Integrative Medicine 28(8):693-701(2022)
DOI：

Xin XU, Xiao-fang XIE, Yan-hong DONG, et al. Ginsenoside Rg₁ Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro. [J]. Chinese Journal of Integrative Medicine 28(8):693-701(2022) DOI： 10.1007/s11655-022-3509-0.

摘要

目的:

2

探讨人参皂苷Rg1 (Rg1) 和乌头碱 (AC) 对乳鼠心肌细胞 (NRCMs) 和戊巴比妥钠 (PS) 诱导的受损NRCMs的协同作用机制.

方法:

2

药物暴露1h后

用MTT法分别筛选出AC的毒性、无毒性和有效剂量

及Rg1对正常和受损NRCMs的最适配伍浓度. 然后

筛选出的不同浓度的AC单独或与Rg1配伍

与正常或受损的NRCMs 共同孵育1小时

观察细胞活性、细胞超微结构、凋亡、酸性磷酸酶 (ACP) 和乳酸脱氢酶 (LDH) 水平、细胞内钠离子[Na

+

]、钾离子[K

+

]和钙离子[Ca

2+

]水平以及Nav1.5、Kv4.2和RyR2基因的表达.

结果:

2

对于正常NRCMs

3000μmol/L AC显著抑制细胞活力 (

P

<

0.01)

促进细胞凋亡

破坏细胞结构 (

P

<

0.05)

低于3000μmol/L的低剂量AC和AC与Rg1的配伍对NRCMs的毒性较小. 与AC单独作用于NRCMs比较

3000μmol/L和10μmol/L AC与1μmol/L Rg1配伍显著降低细胞内Ca

2+

水平 (

P

<

0.01和

P

<

0.05)

3000μmol/L AC与1μmol/L Rg1配伍通过调节Nav1.5和RyR2表达显著降低细胞内Ca

2+

水平 (

P

<

0.01) . 对于受损NRCMs

1500μmol/L AC加重了细胞损伤 (

P

<

0.01)

0.1μmol/L和0.001μmol/L AC对受损NRCMs具有一定的保护作用. 与AC单独作用比较

Rg1与AC的配伍减少了细胞损伤

0.1μmol/L AC与1μmol/L Rg1配伍显著抑制细胞内Na

+

水平 (

P

<

0.05)

1500μmol/L AC与1μmol/L Rg1配伍通过调节受损NRCMs中Nav1.5、Kv4.2、RyR2的表达显著抑制细胞内K+水平 (

P

<

0.01) .

结论:

2

Rg1通过调节[Na

+

]、[K

+

]和[Ca

2+

]离子通道

抑制了AC的心脏毒性

增强了AC的强心作用.

Abstract

Objective:

2

To explore the synergic mechanism of ginsenoside Rg1 (Rg

1

) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced damaged NRCMs.

Methods:

2

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 [Ca

2+

] levels

and Nav1.5

Kv4.2

and RyR

2

genes expressions in each group were examined.

Results:

2

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 μmol/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 μmol/L AC with 1 μmol/L Rg

1

significantly decreased the level of intracellular Ca

2+

(

P

<

0.01 or

P

<

0.05)

and the co-treatment of 3000 μmol/L AC with 1 μmol/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 μmol/L AC aggravated cell damage (

P

<

0.01)

and 0.1 and 0.001 μmol/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 μmol/L AC with 1 μmol/L Rg

1

significantly inhibited the level of intracellular Na

+

(

P

<

0.05)

1500 μmol/L AC with 1 μmol/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:

2

Rg

1

inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of [Na

+

]

[K

+

]

and [Ca

2+

].

关键词

Keywords

aconitineginsenoside Rg1compatibilityion channel pathwaycardiomyocytes

references

Sun XL, Zhang B, Wang SH, Liu SY, Zhou QY. Analysis of the rule of TCM compatibility in TCM prescriptions containing Ginseng Radix et Rhizoma in ancient books for Xiaoke Bing.Evid Based Complement Alternat Med 2020;2020:9472304.

Xu YW, Yang L, Liang K, An R, Wang XH, Zhang H.Pharmacokinetic effects of ginsenoside Rg1 on aconitine,benzoylaconine and aconine by UHPLC-MS/MS. Biomed Chromatogr 2020;34:e4793.

Yan X, Wu HJ, Ren JX, Liu YN, Wang SQ, Yang JY, et al. Shenfu Formula reduces cardiomyocyte apoptosis in heart failure rats by regulating microRNAs. J Ethnopharmacol 2018;227:105-112.

Guo ZJ, Li CS. Therapeutic effects of Shenfu Injection on post-cardiac arrest syndrome. Chin J Integr Med 2013;19:716-720.

Xu ZM, Li CB, Liu QL, Li P, Yang H. Ginsenoside Rg1 prevents doxorubicin-induced cardiotoxicity through the inhibition of autophagy and endoplasmic reticulum stress in mice. Int J Mol Sci 2018;19:3658.

Xu ZM, Li CB, Liu QL, Yang H, Li P. Ginsenoside Rg1 protects H9c2 cells against nutritional stress-induced injury via aldolase/AMPK/PINK1 signalling. J Cell Biochem 2019;120:18388-18397.

Li L, Pan CS, Yan L, Cui YC, Liu YY, Mu HN, et al. Ginsenoside Rg1 ameliorates rat myocardial ischemia-reperfusion injury by modulating energy metabolism pathways. Front Physiol 2018;9:78.

Li QH, Xiang Y, Chen Y, Tang Y, Zhang Y. Ginsenoside Rg1 protects cardiomyocytes against hypoxia/reoxygenation injury via activation of Nrf2/HO-1 signaling and inhibition of JNK. Cell Physiol Biochem 2017;44:21-23.

Zhu C, Wang Y, Liu H, Mu HM, Lu Y, Zhang JY, et al. Oral administration of ginsenoside Rg1 prevents cardiac toxicity induced by doxorubicin in mice through anti-apoptosis.Oncotarget 2017;8:83792-83801.

Luo M, Yan DS, Sun QS, Tao JL, Xu L, Sun H, et al.Ginsenoside Rg1 attenuates cardiomyocyte apoptosis and inflammation via the TLR4/NF-kB/NLRP3 pathway. J Cell Biochem 2020;121:2994-3004.

Li X, Gu L, Yang L, Zhang D, Shen J. Aconitine: a potential novel treatment for systemic lupus erythematosus. J Pharmacol Sci 2017;133:115-121.

Gao X, Zhang X, Hu J, Xu X, Zuo Y, Wang Y, et al.Aconitine induces apoptosis in H9c2 cardiac cells via mitochondria-mediated pathway. Mol Med Rep 2018;17:284-292.

Chan TY. Aconite poisoning. Clin Toxicol (Phila) 2009;47:279-285.

Chan TY. Aconite poisoning presenting as hypotension and bradycardia. Hum Exp Toxicol 2009;28:795-797.

Smith SW, Shah RR, Hunt JL, Herzog CA. Bidirectional ventricular tachycardia resulting from herbal aconite poisoning.Ann Emerg Med 2005;45:100-101.

Yim KM, Tse ML, Lau FL. Reversible intraventricular conduction defect in aconitine poisoning. Singapore Med J 2009;50:e302-e305.

Wang SY, Wang GK. Voltage-gated sodium channels as primary targets of diverse lipid-soluble neurotoxins. Cell Signal 2003;15:151-159.

Wright SN. Comparison of aconitine-modified human heart(hH1) and rat skeletal (mu1) muscle Na+ channels: an important role for external Na+ ions. J Physiol 2002;538:759-771.

Li Y, Tu D, Xiao H, Du Y, Zou A, Liao Y, et al. Aconitine blocks HERG and Kv1.5 potassium channels. J Ethnopharmacol 2010;131:187-195.

Wang YJ, Chen BS, Lin MW, Lin AA, Peng H, Sung RJ, et al.Time-dependent block of ultrarapid-delayed rectifier K+ currents by aconitine, a potent cardiotoxin, in heart-derived H9c2 myoblasts and in neonatal rat ventricular myocytes. Toxicol Sci 2008;106:454-463.

Fu M, Wu M, Wang JF, Qiao YJ, Wang Z. Disruption of the intracellular Ca2+ homeostasis in the cardiac excitation-contraction coupling is a crucial mechanism of arrhythmic toxicity in aconitine-induced cardiomyocytes. Biochem Biophys Res Commun 2007;354:929-936.

Zhang Y, Yu L, Jin W, Fan H, Li M, Zhou T, et al. Reducing toxicity and increasing efficiency: aconitine with liquiritin and glycyrrhetinic acid regulate calcium regulatory proteins in rat mrocardial cell. Afr J Tradit Complement Altern Med 2017;14:69-79.

Tang L, Gong Y, Lv C, Ye L, Liu L, Liu Z. Pharmacokinetics of aconitine as the targeted marker of Fuzi (Aconitum carmichaeli)following single and multiple oral administrations of Fuzi extracts in rat by UPLC/MS/MS. J Ethnopharmacol 2012;141:736-741.

Xie X. Study on the mechanism of aconite cardiotoxicity[Dissertation]. Chendu: Chengdu University of Traditional Chinese Medicien;2012.

Zou B. Ion channel profiling to advance drug discovery and development. Drug Discov Today Technol 2015;18:18-23.

Kitaguchi T, Moriyama Y, Taniguchi T, Maeda S, Ando H, Uda T,et al. CSAHi study: detection of drug-induced ion channel/receptor responses, QT prolongation, and arrhythmia using multi-electrode arrays in combination with human induced pluripotent stem cell-derived cardiomyocytes. J Pharmacol Toxicol Methods 2017;85:73-81.

Landstrom AP, Dobrev D, Wehrens XHT. Calcium signaling and cardiac arrhythmias. Circ Res 2017;120:1969-1993.

Tan XQ, Cheng XL, Zhang L, Wu BW, Liu QH, Meng J, et al. Multi-walled carbon nanotubes impair Kv4.2/4.3 channel activities, delay membrane repolarization and induce bradyarrhythmias in the rat. PLoS One 2014;9:e101545.

Marchi S, Patergnani S, Missiroli S, Morciano G, Rimessi A,Wieckowski MR, et al. Mitochondrial and endoplasmic reticulum calcium homeostasis and cell death. Cell Calcium 2018;69:62-72.

Jiang X, Gao L, Zhang Y, Wang G, Liu Y, Yan C. A comparison of the effects of ketamine, chloral hydrate and pentobarbital sodium anesthesia on isolated rat hearts and cardiomyocytes. J Cardiovasc Med (Hagerstown) 2011;12:732-735.

More>

0

Views

0

Downloads

0

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Related Articles

Ginsenoside Rb1 Ameliorates Autophagy of Hypoxia Cardiomyocytes from Neonatal Rats via AMP-Activated Protein Kinase Pathway

Related Author

No data

Related Institution

Department of Cardiology, the People's Hospital of China Medical University, the People's Hospital of Liaoning Province

International Education College, Shenyang Normal University

Department of Cardiology, the First Affiliated Hospital of Dalian Medical University

Address：1 Caochang, xiyuan, Beijing, People's Republic of China Postal code：100091
Tel：010-62886827, 62877592 Fax：010-62874291
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备05067934号-1 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰