Ginsenoside Rg1 Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro.
10.1007/s11655-022-3509-0
- Author:
Xin XU
1
;
Xiao-Fang XIE
1
;
Yan-Hong DONG
2
;
Hui-Qiong ZHANG
1
;
Cheng PENG
3
Author Information
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.
3. State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School of Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. cdtcmpengcheng@126.com.
- Publication Type:Journal Article
- Keywords:
aconitine;
cardiomyocytes;
compatibility;
ginsenoside Rg1;
ion channel pathway
- MeSH:
Aconitine/pharmacology*;
Animals;
Apoptosis;
Cardiotonic Agents/pharmacology*;
Cardiotoxicity/drug therapy*;
Cell Survival;
Ginsenosides/pharmacology*;
Rats
- From:
Chinese journal of integrative medicine
2022;28(8):693-701
- CountryChina
- Language:English
-
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+].
