Bingying Deng , Guoyong Zhang , Yixuan Zeng , Nireng Li , Changlei Hu , Mingjie Pang , Sifan Lu , Yufeng Gu , Guanghong Chen , Yingchun Zhou , Yi Liu , Yue Hua
{"title":"瓜蒌解百半夏汤通过激活乙醛脱氢酶2抑制小鼠心肌梗死后的心脏凋亡","authors":"Bingying Deng , Guoyong Zhang , Yixuan Zeng , Nireng Li , Changlei Hu , Mingjie Pang , Sifan Lu , Yufeng Gu , Guanghong Chen , Yingchun Zhou , Yi Liu , Yue Hua","doi":"10.1016/j.jep.2024.119143","DOIUrl":null,"url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Cardiac apoptosis has been reported to be involved in the development of Heart failure (HF) after Myocardial infarction (MI). As a traditional Chinese medicine with cardioprotective properties, Gualou Xiebai Banxia Decoction (GXBD) is therapeutically effective in treating MI. However, whether GXBD regulates cardiac apoptosis in HF after MI remains unknown, and the underlying mechanisms still unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to explore the effects and potential mechanisms of GXBD on cardiac apoptosis after MI.</div></div><div><h3>Materials and methods</h3><div>The MI model was constructed by ligating the left anterior descending coronary artery (LAD) in mice. The cardioprotective effects of GXBD were determined by echocardiography, masson staining, and haematoxylin and eosin (HE) staining. Bioinformatics analysis and network Pharmacology were used to explore the underlying molecular mechanisms of GXBD in MI. The effects of GXBD on cardiomyocyte apoptosis as well as the ALDH2 were examined by TUNEL staining, Immunohistochemistry (IHC), and Western blot (WB). Additionally, the effects of GXBD on oxidative stress, apoptosis and the ALDH2 in H9c2 cells were investigated using reactive oxygen species (ROS) detection, Hoechst33342/PI stainingand and WB. Moreover, the effects of suppressing and overexpressing ALDH2 in H9c2 cells were further examined.</div></div><div><h3>Results</h3><div>Target prediction analysis showed that ALDH2 was a key target of GXBD which could ameliorate myocardial infarction. GXBD dose-dependently reduced cardiomyocyte apoptosis and ventricular dysfunction. In vivo experiments, GXBD activated ALDH2 enzymatic activity and inhibited the expression levels of Bax, Bcl-2, Cleaved Caspase 3, and Caspase 9. In vitro experiments, GXBD inhibited apoptosis in H9c2 cells. The inhibitory effects of GXBD on these were at least partially attributed to ALDH2 activation while silencing of ALDH2 significantly reversed these inhibitory effects of GXBD.</div></div><div><h3>Conclusion</h3><div>GXBD exerts inhibitory effects on cardiomyocyte apoptosis in mice after MI and suppresses H9c2 cells oxidative stress and apoptosis through activation of the enzyme activity of ALDH2.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119143"},"PeriodicalIF":4.8000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Gualou Xiebai Banxia Decoction suppresses cardiomyocyte apoptosis in mice after myocardial infarction through activation of acetaldehyde dehydrogenase 2\",\"authors\":\"Bingying Deng , Guoyong Zhang , Yixuan Zeng , Nireng Li , Changlei Hu , Mingjie Pang , Sifan Lu , Yufeng Gu , Guanghong Chen , Yingchun Zhou , Yi Liu , Yue Hua\",\"doi\":\"10.1016/j.jep.2024.119143\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Ethnopharmacological relevance</h3><div>Cardiac apoptosis has been reported to be involved in the development of Heart failure (HF) after Myocardial infarction (MI). As a traditional Chinese medicine with cardioprotective properties, Gualou Xiebai Banxia Decoction (GXBD) is therapeutically effective in treating MI. However, whether GXBD regulates cardiac apoptosis in HF after MI remains unknown, and the underlying mechanisms still unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to explore the effects and potential mechanisms of GXBD on cardiac apoptosis after MI.</div></div><div><h3>Materials and methods</h3><div>The MI model was constructed by ligating the left anterior descending coronary artery (LAD) in mice. The cardioprotective effects of GXBD were determined by echocardiography, masson staining, and haematoxylin and eosin (HE) staining. Bioinformatics analysis and network Pharmacology were used to explore the underlying molecular mechanisms of GXBD in MI. The effects of GXBD on cardiomyocyte apoptosis as well as the ALDH2 were examined by TUNEL staining, Immunohistochemistry (IHC), and Western blot (WB). Additionally, the effects of GXBD on oxidative stress, apoptosis and the ALDH2 in H9c2 cells were investigated using reactive oxygen species (ROS) detection, Hoechst33342/PI stainingand and WB. Moreover, the effects of suppressing and overexpressing ALDH2 in H9c2 cells were further examined.</div></div><div><h3>Results</h3><div>Target prediction analysis showed that ALDH2 was a key target of GXBD which could ameliorate myocardial infarction. GXBD dose-dependently reduced cardiomyocyte apoptosis and ventricular dysfunction. In vivo experiments, GXBD activated ALDH2 enzymatic activity and inhibited the expression levels of Bax, Bcl-2, Cleaved Caspase 3, and Caspase 9. In vitro experiments, GXBD inhibited apoptosis in H9c2 cells. The inhibitory effects of GXBD on these were at least partially attributed to ALDH2 activation while silencing of ALDH2 significantly reversed these inhibitory effects of GXBD.</div></div><div><h3>Conclusion</h3><div>GXBD exerts inhibitory effects on cardiomyocyte apoptosis in mice after MI and suppresses H9c2 cells oxidative stress and apoptosis through activation of the enzyme activity of ALDH2.</div></div>\",\"PeriodicalId\":15761,\"journal\":{\"name\":\"Journal of ethnopharmacology\",\"volume\":\"339 \",\"pages\":\"Article 119143\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-11-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of ethnopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0378874124014429\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378874124014429","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Gualou Xiebai Banxia Decoction suppresses cardiomyocyte apoptosis in mice after myocardial infarction through activation of acetaldehyde dehydrogenase 2
Ethnopharmacological relevance
Cardiac apoptosis has been reported to be involved in the development of Heart failure (HF) after Myocardial infarction (MI). As a traditional Chinese medicine with cardioprotective properties, Gualou Xiebai Banxia Decoction (GXBD) is therapeutically effective in treating MI. However, whether GXBD regulates cardiac apoptosis in HF after MI remains unknown, and the underlying mechanisms still unclear.
Aim of the study
This study aimed to explore the effects and potential mechanisms of GXBD on cardiac apoptosis after MI.
Materials and methods
The MI model was constructed by ligating the left anterior descending coronary artery (LAD) in mice. The cardioprotective effects of GXBD were determined by echocardiography, masson staining, and haematoxylin and eosin (HE) staining. Bioinformatics analysis and network Pharmacology were used to explore the underlying molecular mechanisms of GXBD in MI. The effects of GXBD on cardiomyocyte apoptosis as well as the ALDH2 were examined by TUNEL staining, Immunohistochemistry (IHC), and Western blot (WB). Additionally, the effects of GXBD on oxidative stress, apoptosis and the ALDH2 in H9c2 cells were investigated using reactive oxygen species (ROS) detection, Hoechst33342/PI stainingand and WB. Moreover, the effects of suppressing and overexpressing ALDH2 in H9c2 cells were further examined.
Results
Target prediction analysis showed that ALDH2 was a key target of GXBD which could ameliorate myocardial infarction. GXBD dose-dependently reduced cardiomyocyte apoptosis and ventricular dysfunction. In vivo experiments, GXBD activated ALDH2 enzymatic activity and inhibited the expression levels of Bax, Bcl-2, Cleaved Caspase 3, and Caspase 9. In vitro experiments, GXBD inhibited apoptosis in H9c2 cells. The inhibitory effects of GXBD on these were at least partially attributed to ALDH2 activation while silencing of ALDH2 significantly reversed these inhibitory effects of GXBD.
Conclusion
GXBD exerts inhibitory effects on cardiomyocyte apoptosis in mice after MI and suppresses H9c2 cells oxidative stress and apoptosis through activation of the enzyme activity of ALDH2.
期刊介绍:
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.