[Retracted] Tongyang Huoxue Decoction (TYHX) Ameliorating Hypoxia/Reoxygenation‐Induced Disequilibrium of Calcium Homeostasis and Redox Imbalance via Regulating Mitochondrial Quality Control in Sinoatrial Node Cells

Evidence-Based Complementary and Alternative Medicine

Hua

et al. 2022

Background. Myocardial ischemia (MI) is a major public health problem with high mortality and morbidity worldwide. Huoxue Wentong formula (HX), a traditional Chinese medicine (TCM) formula, exhibits unambiguous effects on treating MI and preventing cardiovascular diseases. However, the molecular mechanism of the therapeutic effects of HX on MI remains largely unknown. Objective. This study combined microbiology, metabolomics, and network pharmacology to explore the relationship between the gut microbiota and its metabolites in MI rats and the efficacy of HX. Methods. First, the MI rat model was established by ligation of left anterior descending. Echocardiography, Masson’s staining, and hematoxylin and eosin staining were used to evaluate the effect of HX on MI. Then, fecal metabolomics and 16S rRNA sequencing were used to obtain the microbial and metabolic characteristics of HX on MI. After that, network pharmacology was used to predict the target and action pathway of HX in treating MI. Finally, the relationship between fecal metabolites and target was explored through bioinformatics. Results. HX can improve the cardiac function and ameliorated myocardial fibrosis in MI rats. Moreover, HX can affect the gut microbiota community and metabolites of MI rats, especially Bacteroides, Deferribacteres, Ruminococcus_sp._zagget7, Acidobacteria, daidzein, L-lactic acid, and malate. Network pharmacology found that HX can function through tumor necrosis factor (TNF), tumor protein p53 (TP53), interleukin 6 (IL6), vascular endothelial growth factor A (VEGFA), fos proto-oncogene (FOS), bcl2-associated X (BAX), myeloperoxidase (MPO), PI3K-Akt signaling pathways, and HIF-1 signaling pathway. The mechanism study showed that the anti-MI effect of HX was related to valine, leucine, and isoleucine biosynthesis, fatty acid biosynthesis, and arachidonic acid metabolism. Conclusion. This study demonstrates that HX treated MI rats in a multitarget and multipathway manner. Its mechanism is related to the change of gut microbiota and the regulation of valine, leucine and isoleucine biosynthesis, fatty acid biosynthesis, and arachidonic acid metabolism.

Section: Discussionmentioning

confidence: 99%

Integrated Gut-Heart Axis and Network Pharmacology to Reveal the Mechanisms of the Huoxue Wentong Formula Against Myocardial Ischemia

Lin

Evidence-Based Complementary and Alternative Medicine

Hua

et al. 2022

“…In addition to the active ingredients of traditional Chinese medicine, the compound preparation of traditional Chinese medicine can also have a certain regulatory effect on the interaction mechanism of mitochondrial dynamics and mitophagy. Tongyang Huoxue Recipe, a traditional Chinese medicine compound, can protect sinoatrial node cells under stress through PINK/parkin-mediated mitophagy, and can also inhibit DRP1-mediated mitochondrial fusion/fission dysfunction, increase mitochondrial membrane potential, maintain calcium homeostasis, and inhibits oxidative stress damage (194). Zishen Huoxue Decoction is an effective compound for the treatment of patients with coronary heart disease.…”

Section: Mitochondrial Targeted Natural Medicines Therapymentioning

confidence: 99%

Mitochondrial Dynamics and Mitophagy in Cardiometabolic Disease

Lin

Duan

Front. Cardiovasc. Med.

et al. 2022

Mitochondria play a key role in cellular metabolism. Mitochondrial dynamics (fusion and fission) and mitophagy, are critical to mitochondrial function. Fusion allows organelles to share metabolites, proteins, and mitochondrial DNA, promoting complementarity between damaged mitochondria. Fission increases the number of mitochondria to ensure that they are passed on to their offspring during mitosis. Mitophagy is a process of selective removal of excess or damaged mitochondria that helps improve energy metabolism. Cardiometabolic disease is characterized by mitochondrial dysfunction, high production of reactive oxygen species, increased inflammatory response, and low levels of ATP. Cardiometabolic disease is closely related to mitochondrial dynamics and mitophagy. This paper reviewed the mechanisms of mitochondrial dynamics and mitophagy (focus on MFN1, MFN2, OPA1, DRP1, and PINK1 proteins) and their roles in diabetic cardiomyopathy, myocardial infarction, cardiac hypertrophy, heart failure, atherosclerosis, and obesity.

“…The degradation of the fusion protein Mfn1/2 up to a certain level can maintain the mitochondria in a fission state, which may be necessary for mitophagy. Increased levels of mitophagy protect cardiomyocytes under certain stress conditions [ 106 ]. For example, Parkin-mediated mitophagy protects against high glucose- and palmitate-induced cardiomyocyte injury.…”

Section: Mitophagymentioning

confidence: 99%

“…Natural medicines and their active compounds have multitarget comprehensive curative effects [ 136 , 137 ] ( Figure 7 ). Many natural medicines and their active compounds, such as aconite, bupleurum, and astragalus, protect cardiomyocytes, enhance myocardial contractility, dilate blood vessels, induce diuresis, and reduce ventricular remodeling; these are widely used in the treatment of heart failure [ 12 , 106 ]. Studies have also found that natural active compounds extracted from traditional natural medicinal plants have anti-inflammatory, antioxidative, and antiapoptotic actions, while improving fatty acid oxidation and autophagic effects [ 130 , 136 ].…”

Section: Natural Medicinal Plants and Active Ingredients In The Regul...mentioning

confidence: 99%

Protective Effect of Natural Medicinal Plants on Cardiomyocyte Injury in Heart Failure: Targeting the Dysregulation of Mitochondrial Homeostasis and Mitophagy

Oxidative Medicine and Cellular Longevity

Liu

2022

Self Cite

Heart failure occurs because of various cardiovascular pathologies, such as coronary artery disease or cardiorenal syndrome, eventually reaching end-stage disease. Various factors contribute to cardiac structural or functional changes that result in systolic or diastolic dysfunction. Several studies have confirmed that the key factor in heart failure progression is myocardial cell death, and mitophagy is the major mechanism regulating myocardial cell death in heart failure. The clinical mechanisms of heart failure are well understood in practice. However, the essential role of mitophagic regulation in heart failure has only recently received widespread attention. Receptor-mediated mitophagy is involved in various mitochondrial processes like oxidative stress injury, energy metabolism disorders, and calcium homeostasis, which are also the main causes of heart failure. Understanding of the diverse regulatory mechanisms in mitophagy and the complexity of its pathophysiology in heart failure remains incomplete. Related studies have found that various natural medicinal plants and active ingredients, such as flavonoids and saponins, can regulate mitophagy to a certain extent, improve myocardial function, and protect myocardial cells. This review comprehensively covers the relevant mechanisms of different types of mitophagy in regulating heart failure pathology and controlling mitochondrial adaptability to stress injury. Further, it explores the relationship between mitophagy and cardiac ejection dysfunction. Natural medicinal plant-targeted regulation strategies and scientific evidence on mitophagy were provided to elucidate current and potential strategies to apply mitophagy-targeted therapy for heart failure.