Hezi inhibits Tiebangchui-induced cardiotoxicity and preserves its anti-rheumatoid arthritis effects by regulating the pharmacokinetics of aconitine and deoxyaconitine

Liu, Xianfeng; Tao, Honglin; Tian, Ruimin; Huang, Weicai; Zhang, Tao; Liu, Yue; Zhang, Yi; Meng, Xianli

doi:10.1016/j.jep.2022.115915

Cited by 3 publications

(3 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with the research results of Wang et al [24] Acon caused damage to rat H9C2 cardiomyocytes and increased AST levels. Liu et al [25] used Acon to induce myocardial injury model in rats to study detoxi cation drugs. The levels of LDH and CK-MB increased in the serum of rats with myocardial injury.…”

Section: Discussionmentioning

confidence: 99%

Aconitine promotes myocardial damage in rats by activating JNK1/2 pathway

Hu,

Huang,

et al. 2024

Preprint

View full text Add to dashboard Cite

Background Aconitine (Acon) poisoning can cause arrhythmia and myocardial damage, but the specific mechanism of myocardial damage caused by acon poisoning is still unclear. This study explored the mechanism of myocardial damage caused by acute acon poisoning by constructing a rat acuteacon poisoning model. Methods First, the rats were divided into 4 groups (n = 9): control group, Acet group, Acon-1 mg group, and Acon-2 mg group (Detect 3 rats in each group at 1/2/3 h; 36 rats in total), When conducted the second part of the experiment to examine the role of the JNK pathway in acon poisoning, the rats were divided into 5 groups (n=3): control group, Acon-2 mg group, DMSO group, Acon-2 mg+SP600125 group, and Acon-2 mg+Anis group (15 rats in total). Rat model of acute acon poisoning was constructed by intragastric administration. Electrocardiogram tracings were used to record rat heart rhythm changes, and H&E staining Masson staining were performed to evaluate myocardial pathological damage and myocardial fibrosis. The expression levels of cardiac enzymes and cardiac proteins in venous blood were detected by ELISA Kits. The expression levels of JNK1 / 2 phosphorylation proteins were detected by Western blotting. Results In this study, 1/3/6 hour after Acon-1mg and Acon-2mg was perfused to the rats, the electrocardiogram results showed that the rats in theAcon group (the Acon-1mg group and the Acon-2mg group) developed one or more ventricular arrhythmias. In myocardial tissue, the arrangement of myocardial fibers and myocardial cells is disordered, myocardial cells are swollen and degenerated, and the cytoplasm of myocardial fibers is rounded and vacuolated; myocardial collagen hyperplasia is abnormal, and myocardial fibrosis occurs. At the same time, the expression levels of cardiac enzymes and cardiac proteins in venous blood increased. In addition, JNK1/2 phosphorylation levels increased. Further study showed that use of a JNK inhibitor (SP600125) partially reversed Acon's damage to rat myocardium. Conclusions Taken together, these results indicate that JNK1 / 2 phosphorylation is involved in the development of myocardial damage induced by acute Acon poisoning. In addition, the intervention effect of JNK specific inhibitor on myocardial damage induced by acute Acon poisoning was obvious, which may provide new insights into the important role of inhibiting the JNK1/2 pathway in alleviating myocardial damage caused by acute Acon intoxication.

show abstract

Section: Discussionmentioning

confidence: 99%

Aconitine promotes myocardial damage in rats by activating JNK1/2 pathway

Hu,

Huang,

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…3) CF can play a role in reducing toxicity by affecting the absorption, distribution and metabolic process of aconitums in the body. For absorption: the pharmacokinetics of alkaloids can be changed after the processing of aconitums or the compatibility with CF, and the absorption level and absorption rate of alkaloids are reduced, thus reducing the toxicity ( Zhi et al, 2020b ; Liu et al, 2023 ). For distribution: CF can reduce the distribution of DDAs in various organs and tissues, and the tannins can bind to DDAs and slowly distribute and eliminate them in the body to play a role in detoxification ( Wang et al, 2002 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated virtual screening and in vitro studies for exploring the mechanism of triterpenoids in Chebulae Fructus alleviating mesaconitine-induced cardiotoxicity via TRPV1 channel

Song,

Mi,

Zhao

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

Background: In traditional Mongolian or Tibetan medicine in China, Chebulae Fructus (CF) is widely used to process or combine with aconitums to decrease the severe toxicity of aconitums. Researches in this area have predominantly focused on tannins, with few research on other major CF components for cardiotoxicity mitigation. The present study aimed to clarify whether triterpenoids can attenuate the cardiotoxicity caused by mesaconitine (MA) and investigate the mechanism of cardiotoxicity attenuation.Methods: Firstly, the pharmacophore model, molecular docking, and 3D-QSAR model were used to explore the mechanism of CF components in reducing the toxicity of MA mediated by the TRPV1 channel. Then three triterpenoids were selected to verify whether the triterpenoids had the effect of lowering the cardiotoxicity of MA using H9c2 cells combined with MTT, Hoechst 33258, and JC-1. Finally, Western blot, Fluo-3AM, and MTT assays combined with capsazepine were used to verify whether the triterpenoids reduced H9c2 cardiomyocyte toxicity induced by MA was related to the TRPV1 channel.Results: Seven triterpenoids in CF have the potential to activate the TRPV1 channel. And they exhibited greater affinity for TRPV1 compared to other compounds and MA. However, their activity was relatively lower than that of MA. Cell experiments revealed that MA significantly reduced H9c2 cell viability, resulting in diminished mitochondrial membrane potential and nuclear pyknosis and damage. In contrast, the triterpenoids could improve the survival rate significantly and counteract the damage of MA to the cells. We found that MA, arjungenin (AR), and maslinic acid (MSA) except corosolic acid (CRA) upregulated the expression of TRPV1 protein. MA induced a significant influx of calcium, whereas all three triterpenoids alleviated this trend. Blocking the TRPV1 channel with capsazepine only increased the cell viability that had been simultaneously treated with MA, and AR, or MSA. However, there was no significant difference in the CRA groups treated with or without capsazepine.Conclusion: The triterpenoids in CF can reduce the cardiotoxicity caused by MA. The MSA and AR function as TRPV1 agonists with comparatively reduced activity but a greater capacity to bind to TRPV1 receptors, thus antagonizing the excessive activation of TRPV1 by MA.

show abstract

“…Prior research has demonstrated that AC can exert a cardioprotective effect in cases of myocardial ischemia through the regulation of nuclear respiratory factor-2 (NRF-2)-mediated anti-inflammatory signaling and nuclear transcription factor-κB (NF-κB)-mediated pro-inflammatory signaling ( Liu et al, 2023 ). Furthermore, AC has the capability to regulate the levels of nitric oxide synthase, thereby enhancing blood circulation in the infarction area and subsequently mitigating myocardial damage resulting from acute myocardial infarction ( Mitamura et al, 2002 ; Wang et al, 2022a ).…”

Section: Pharmacological Activities Of Acmentioning

confidence: 99%

Aconitine and its derivatives: bioactivities, structure-activity relationships and preliminary molecular mechanisms

Zhao,

Tian,

Geng

et al. 2024

Front. Chem.

View full text Add to dashboard Cite

Aconitine (AC), which is the primary bioactive diterpene alkaloid derived from Aconitum L plants, have attracted considerable interest due to its unique structural feature. Additionally, AC demonstrates a range of biological activities, such as its ability to enhance cardiac function, inhibit tumor growth, reduce inflammation, and provide analgesic effects. However, the structure-activity relationships of AC are remain unclear. A clear understanding of these relationships is indeed critical in developing effective biomedical applications with AC. In line with these challenges, this paper summarized the structural characteristics of AC and relevant functional and bioactive properties and the structure-activity relationships presented in biomedical applications. The primary temporal scope of this review was established as the period spanning from 2010 to 2023. Subsequently, the objective of this review was to provide a comprehensive understanding of the specific action mechanism of AC, while also exploring potential novel applications of AC derivatives in the biomedical field, drawing upon their structural characteristics. In conclusion, this review has provided a comprehensive analysis of the challenges and prospects associated with AC in the elucidation of structure-bioactivity relationships. Furthermore, the importance of exploring modern biotechnology approaches to enhance the potential biomedical applications of AC has been emphasized.

show abstract

Hezi inhibits Tiebangchui-induced cardiotoxicity and preserves its anti-rheumatoid arthritis effects by regulating the pharmacokinetics of aconitine and deoxyaconitine

Cited by 3 publications

References 18 publications

Aconitine promotes myocardial damage in rats by activating JNK1/2 pathway

Aconitine promotes myocardial damage in rats by activating JNK1/2 pathway

Integrated virtual screening and in vitro studies for exploring the mechanism of triterpenoids in Chebulae Fructus alleviating mesaconitine-induced cardiotoxicity via TRPV1 channel

Aconitine and its derivatives: bioactivities, structure-activity relationships and preliminary molecular mechanisms

Contact Info

Product

Resources

About