Mechanism of Aconiti Kusnezoffii Radix Processed with Chebulae Fructus Against H9c2 Cardiomyocyte Toxicity Based on TRPV1 Channel
10.13422/j.cnki.syfjx.20211748
- VernacularTitle:基于TRPV1通道分析诃子制草乌减轻H9c2心肌细胞毒性的作用机制
- Author:
Shu HAN
1
;
Li-yuan BAO
1
;
Kai-yang LIU
1
;
Xi-tao HAN
1
;
Ya-nan TANG
1
;
Zi-qin LIU
1
;
Hong-yue WANG
1
;
Ang-ran FAN
1
;
Fei LI
1
;
Hong DU
1
Author Information
1. Beijing University of Chinese Medicine,Beijing 100029,China
- Publication Type:Journal Article
- Keywords:
raw Aconiti Kusnezoffii Radix;
Aconiti Kusnezoffii Radix processed with Chebulae Fructus;
transient receptor potential vanilloid 1 (TRPV1);
H9c2 cardiomyocytes;
detoxification by processing;
polymerase chain reaction (PCR);
lactate dehydrogenase (LDH)
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(1):173-181
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the role of transient receptor potential vanilloid 1 (TRPV1) channel in reducing cardiomyocyte toxicity of Aconiti Kusnezoffii Radix processed with Chebulae Fructus. MethodH9c2 cardiomyocytes cultured in vitro were used as a model to assess cell viability by methyl thiazolyl tetrazolium (MTT) assay, the expression of TRPV1 mRNA was detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and the leakage rate of lactate dehydrogenase (LDH), the changes of nucleus, reactive oxygen species (ROS), mitochondrial membrane potential and Ca2+ contents were detected by enzyme linked immunosorbent assay (ELISA). ResultCompared with the blank group, when the concentration was ≥0.5 g·L-1, the cell viability was significantly decreased (P<0.01), the leakage rate of LDH, the release of ROS and Ca2+ were increased, the mitochondrial membrane potential was decreased, and the nucleus was pyknosis or even broken in raw Aconiti Kusnezoffii Radix and Aconiti Kusnezoffii Radix processed with Chebulae Fructus groups. When the concentration was ≥0.5 g·L-1, compared with the same mass concentration of raw Aconiti Kusnezoffii Radix group, the cell viability increased significantly (P<0.01), the leakage rate of LDH, the release of ROS and Ca2+ decreased, the mitochondrial membrane potential increased, and the nuclear morphology improved in Aconiti Kusnezoffii Radix processed with Chebulae Fructus group. Application of the same mass concentration of raw Aconiti Kusnezoffii Radix to H9c2 cardiomyocytes pretreated with the TRPV1 inhibitor BCTC significantly increased cell viability, decreased leakage rate of LDH, ROS and Ca2+ release, increased mitochondrial membrane potential and improved nuclear pyknosis compared with untreated H9c2 cardiomyocytes. Application of the same mass concentration of Aconiti Kusnezoffii Radix processed with Chebulae Fructus to H9c2 cardiomyocytes pretreated with BCTC decreased cell viability, increased LDH leakage rate, ROS and Ca2+ release, reduced mitochondrial membrane potential compared with untreated H9c2 cardiomyocytes. Real-time PCR results showed that both raw Aconiti Kusnezoffii Radix and Chebulae Fructus decoction could increase the expression of TRPV1 mRNA in cardiomyocytes in a concentration dependent manner. ConclusionRaw Aconiti Kusnezoffii Radix can induce cardiomyocyte apoptosis and cardiotoxicity by activating TRPV1 channel, while Aconiti Kusnezoffii Radix processed with Chebulae Fructus can attenuate the toxicity through TRPV1 channel, which may be related to the synergistic effect of acid components in Chebulae Fructus and alkaloids in Aconiti Kusnezoffii Radix on TRPV1 channel.