期刊：
Frontiers in Medicine,2023年10:1259182 ISSN：2296-858X
通讯作者：
Hu, ZX
作者机构：
[Hu, Zhixi; Li, Lin; Hu, ZX; Hu, Siyuan] Hunan Univ Chinese Med, Domest class Discipline Construct Project Chinese, Changsha, Hunan, Peoples R China.;[Hu, Zhixi; Li, Lin; Hu, ZX] Hunan Univ Chinese Med, Prov Key Lab TCM Diagnost, Changsha, Hunan, Peoples R China.;[Li, Lin] Hunan Engn Technol Res Ctr Med & Funct Food, Changsha, Hunan, Peoples R China.;[Zhong, Senjie; Ye, Jiahao] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China.;[Ye, Jiahao] Hunan Univ Chinese Med, Postgrad Sch, Changsha, Hunan, Peoples R China.
通讯机构：
[Hu, ZX ] H;Hunan Univ Chinese Med, Domest class Discipline Construct Project Chinese, Changsha, Hunan, Peoples R China.;Hunan Univ Chinese Med, Prov Key Lab TCM Diagnost, Changsha, Hunan, Peoples R China.
关键词：
Heart Failure;Danhong injection;Metabolomics;transverse aortic constriction;Chinese medicine (CM)
摘要：
BackgroundHeart failure (HF) is characterized by reduced ventricular filling or ejection function due to organic or non-organic cardiovascular diseases. Danhong injection (DHI) is a medicinal material used clinically to treat HF for many years in China. Although prior research has shown that Danhong injection can improve cardiac function and structure, the biological mechanism has yet to be determined.MethodsSerum metabolic analysis was conducted via ultra-high-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UHPLC-QE/MS) to explore underlying protective mechanisms of DHI in the transverse aortic constriction (TAC)-induced heart failure. Multivariate statistical techniques were used in the research, such as unsupervised principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA). MetaboAnalyst and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to pinpoint pertinent metabolic pathways.ResultsAfter DHI treatment, cardiac morphology and function as well as the metabolism in model rats were improved. We identified 17 differential metabolites and six metabolic pathways. Two biomarkers, PC(18:3(6Z,9Z,12Z)/24:0) and L-Phenylalanine, were identified for the first time as strong indicators for the significant effect of DHI.ConclusionThis study revealed that DHI could regulate potential biomarkers and correlated metabolic pathway, which highlighted therapeutic potential of DHI in managing HF.
作者机构：
[Zhang, Xiang-Zhuo; Huang, Shu-Chun; Li, Jing; Yang, Yang; Kuang, Hui-Fang] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Su, Chang] Hunan Univ Chinese Med, Coll Xiangxing, Changsha 410208, Hunan, Peoples R China.;[Zhang, Qiu-Yan] Hunan Univ Chinese Med, Sch Infirm, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Kuang, Hui-Fang; Su, Chang; Zhang, Xiang-Zhuo; Huang, Shu-Chun; Yang, Yang; Li, Jing] C;[Zhang, Qiu-Yan] S;College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China. Electronic address:;College of Xiangxing, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China. Electronic address:;School Infirmary, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China. Electronic address:
摘要：
Coronary heart disease (CHD) has become the leading cause of mortality, morbidity, and disability worldwide. Though the therapeutic effect of Xuefu Zhuyu Decoction (XFZY) on CHD has been demonstrated in China, the active ingredients and molecular mechanisms of XFZY have not been elucidated. The purpose of the current study is to explore the molecular mechanisms of XFZY in the treatment of CHD via network pharmacology, metabolomics, and experimental validation. First, we established a CHD rat model by permanently ligating the left anterior descending coronary artery (LAD), and evaluated the therapeutic effect of XFZY by hemorheology and histopathology. Second, network pharmacology was employed to screen the active ingredients and potential targets of XFZY for the treatment of CHD. Metabolomic was applied to identify the molecules present in the serum after XFZY treatment. Third, the results of network pharmacology and metabolomics were further analyzed by Cytoscape to elucidate the core ingredients and pathways. Finally, the obtained key pathways were verified by transmission electron microscopy and immunofluorescence assay. The results showed that XFZY was effective in the treatment of CHD in the rat model, and the highest dose exerted the best effect. Network pharmacology analysis revealed 215 active ingredients and 129 key targets associated with XFZY treatment of CHD. These targets were enriched in pathways of cancer, lipid and atherosclerosis, fluid shear stress and atherosclerosis, proteoglycans in cancer, chemical carcinogenesis - receptor activation, HIF-1 signaling, et al. Serum metabolomic identified 1081 metabolites involved in the therapeutic effect of XFZY on CHD. These metabolites were enriched in taurine and hypotaurine metabolism, histidine metabolism, retrograde endocannabinoid signaling pathways, et al. Cytoscape analysis combining the data from serum metabolomic and network pharmacology revealed that energy metabolism as the core pathway for XFZY treatment of CHD. Electron microscope observation identified changes in the level of autophagy in the mitochondrial structure of cardiomyocytes. Immunofluorescence assay showed that the expression levels of autophagy-related proteins LC3-B and P62/SQSTM1 were consistent with the levels of autophagy observed in mitochondria. In conclusion, our findings suggest that the possible mechanisms of XFZY in the treatment of CHD are reducing the level of autophagy, improving energy metabolism, and maintaining mitochondrial homeostasis in cardiomyocytes. Our study also shows that the combined strategies of network pharmacology, metabolomics, and experimental validation may provide a powerful approach for TCM pharmacology study.
作者机构：
[朱梦晨; 刘卓琳; 马心悦; 黄家望] College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China;[李玲; 王康宇; 冯芷莹] College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China;[卢芳国] Medical School of Hunan University of Chinese Medicine, Changsha, 410208, China
通讯机构：
[Li, L.] C;College of Traditional Chinese Medicine, China
