Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

OBJECTIVE: To investigate the inhibitory effect of Zhenwu Decoction on ventricular hypertrophy in rats with uremic cardiomyopathy and explore the mechanism. METHODS: Cardiocytes isolated from suckling rats were divided into control group and indoxyl sulfate (IS) group, and the protein synthesis was assayed with [H]- leucine incorporation and cellular protein expressions were detected using Western blotting. Fifty SD rats were randomly divided into sham operation group, model group, and low- and high-dose Zhenwu Decoction treatment groups, and except for those in the sham operation group, all the rats underwent 5/6 nephrectomy. Four weeks after the operation, the rats in low- and high-dose treatment groups were given Zhenwu Decoction gavage at the dose of 4.5 g/kg and 13.5 g/kg, respectively; the rats in the sham-operated and model groups were given an equal volume of distilled water. After 4 weeks of treatment, serum levels of IS were determined, and cardiac and ventricular mass indexes were measured in the rats; cardiac ultrasound was performed and Western blotting was used to measure the expressions of BNP, p-ERK1/2, p-p38 and p-JNK in the myocardium. RESULTS: Rat cardiomyocytes treated with IS showed significantly enhanced protein synthesis and increased expression levels of BNP, p-erk1/2, and p-p38 as compared with the control cells ( < 0.01), but the expression of p-jnk was comparable between the two groups. In the animal experiment, the rats in the model group showed significantly increased serum creatinine (SCr) and urea nitrogen (BUN) levels, 24-h urine protein (24 hUpro), plasma IS level, left ventricular mass index (LVMI) and whole heart mass index (HMI) compared with those in the sham group ( < 0.01); Both LVESD and LVEDD were significantly reduced and LVAWS, LVAWD, LVPWS and LVPWD were significantly increased in the model rat, which also presented with obvious cardiomyocyte hypertrophy and increased myocardial expressions of BNP, p-ERK1/2, p-p38 and p-jnk ( < 0.01). Compared with the rats in the model group, the rats treated with low-dose and high-dose Zhenwu Decoction had significantly lowered levels of SCr, BUN, 24 hUpro and IS ( < 0.05) and decreased LVMI and HMI; LVESD, LVEDD, LVPWS, LVAWS, and LVAWD were improved more obviously in the high-dose group, and the myocardial expressions of BNP, p-ERK1/2, p-p38 and p-JNK was significantly downregulated after the treatment. CONCLUSIONS Zhenwu Decoctin can reduce plasma IS levels and inhibit ventricular hypertrophy to delay ventricular remodeling in rats with uremic cardiomyopathy.
Animals ; Blood Urea Nitrogen ; Cardiomegaly ; prevention & control ; Cardiomyopathies ; complications ; Creatinine ; blood ; Drugs, Chinese Herbal ; pharmacology ; Heart Ventricles ; Indican ; blood ; pharmacology ; Myocytes, Cardiac ; drug effects ; metabolism ; Nephrectomy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

BACKGROUND AND OBJECTIVES: This study was performed to describe clinical characteristics of patients with left ventriculars (LV) dysfunction and implantable cardioverter-defibrillator (ICD), and to evaluate the effect of ICD therapy on survival in Yeongnam province of Korea. SUBJECTS AND METHODS: From a community-based device registry (9 centers, Yeongnam province, from November 1999 to September 2012), 146 patients with LV dysfunction and an ICD implanted for primary or secondary prophylaxis, were analyzed. The patients were divided into two groups, based on the etiology (73 with ischemic cardiomyopathy and 73 with non-ischemic cardiomyopathy), and indication for the device implantation (36 for primary prevention and 110 for secondary prevention). The cumulative first shock rate, all cause death, and type and mode of death, were determined according to the etiology and indication. RESULTS: Over a mean follow-up of 3.5 years, the overall ICD shock rate was about 39.0%. ICD shock therapy was significantly more frequent in the secondary prevention group (46.4% vs. 16.7%, p=0.002). The cumulative probability of a first appropriate shock was higher in the secondary prevention group (p=0.015). There was no significant difference in the all-cause death, cardiac death, and mode of death between the groups according to the etiology and indication. CONCLUSION: Studies from this multicenter regional registry data shows that in both ischemic and non-ischemic cardiomyopathy patients, the ICD shock therapy rate was higher in the secondary prevention group than primary prevention group.
Cardiomyopathies ; Convulsive Therapy ; Death ; Defibrillators, Implantable* ; Follow-Up Studies ; Heart Failure* ; Heart* ; Humans ; Korea* ; Mortality ; Primary Prevention ; Secondary Prevention ; Shock ; Ventricular Dysfunction, Left

The insertion of implantable cardioverter-defibrillators (ICD) in patients with non-ischemic cardiomyopathy (NICM) has been recommended by recent guidelines. However, current evidence shows limited benefits to inserting ICDs in patients with NICM. Recently, the defibrillator implantation in patients with non-ischemic systolic heart failure (DANISH) trial, a large randomized trial of more than 1,100 patients with NICM, was conducted to compare the primary prevention of all-cause mortality between optimal medical therapy, cardiac resynchronization therapy, and ICD implantation. The DANISH trial revealed no differences in all-cause mortality between the groups after 5 years. However, in patients younger than 68 years of age, the rate of death from any cause was significantly lower in the ICD group compared to the control group. In addition, the rate of sudden cardiac death was lower in the ICD group compared to the control group in patients under 68 years. The results of DANISH will likely change guidelines about the insertion of ICD in patients with NICM, and encourage the use of ICD in patients with NICM.
Cardiac Resynchronization Therapy ; Cardiomyopathies* ; Death, Sudden, Cardiac* ; Defibrillators ; Defibrillators, Implantable* ; Heart Failure, Systolic ; Humans ; Mortality ; Primary Prevention*

A 56-year-old man with an implantable cardioverter-defibrillator (ICD) presented with unexplained heart palpitations, which were usually aggravated after ingesting alcohol. He had a history of coronary artery bypass graft surgery 8 years ago, and an ICD was placed (i.e. a single ventricular shock coil with integrated atrial-sensing rings [VDD ICD lead]) 1.5 years ago for primary prevention of sudden cardiac death associated with ischemic cardiomyopathy. Repeated electrocardiograms and echocardiograms showed no evidence of atrial flutter-fibrillation; this was clearly demonstrated using several atrial electrogram strips during the ICD analysis.
Atrial Fibrillation ; Cardiomyopathies ; Coronary Artery Bypass ; Death, Sudden, Cardiac ; Defibrillators* ; Defibrillators, Implantable ; Electrocardiography ; Electrophysiologic Techniques, Cardiac ; Heart ; Humans ; Middle Aged ; Primary Prevention ; Shock ; Stroke ; Transplants

Implantable cardioverter-defibrillators (ICDs) are an effective treatment strategy for patients with aborted sudden cardiac death (SCD) and ventricular tachyarrhythmias. rimary prevention of SCD is a strategy involving the use of ICDs in patients who are at high risk for, but have not had, any previous events of ventricular arrhythmias or cardiac arrest. Several randomized clinical trials have demonstrated the efficacy of ICDs in the primary prevention of SCD. Therefore, ICD implantation is recommended as a standard of care by the guidelines in patients who have ischemic or nonischemic cardiomyopathy and a low left ventricular ejection fraction. However, the rates of ICD implantation as a primary prevention in Korea is quite low compared to western countries. In this review, we will summarize the results and efficacy of ICDs in the clinical trials about primary prevention of SCD, the current treatment guidelines, and the reimbursement policy of Korean health insurance. We hope that this review will help broaden the recognition of importance of ICD implantation for the primary prevention of SCD.
Arrhythmias, Cardiac ; Cardiomyopathies ; Death, Sudden, Cardiac* ; Defibrillators, Implantable* ; Heart Arrest ; Hope ; Humans ; Insurance, Health ; Korea ; Primary Prevention* ; Standard of Care ; Stroke Volume ; Tachycardia

Angiotensin receptor blockers (ARBs) have organ-protective effects in heart failure and may be also effective in doxorubicin-induced cardiomyopathy (DOX-CMP); however, the efficacy of ARBs on the prevention of DOX-CMP have not been investigated. We performed a preclinical experiment to evaluate the preventive effect of a novel ARB, fimasartan, in DOX-CMP. All animals underwent echocardiography and were randomly assigned into three groups: treated daily with vehicle (DOX-only group, n=22), 5 mg/kg of fimasartan (Low-fima group, n=22), and 10 mg/kg of fimasartan (High-fima group, n=19). DOX was injected once a week for six weeks. Echocardiography and hemodynamic assessment was performed at the 8th week using a miniaturized conductance catheter. Survival rate of the High-fima group was greater (100%) than that of the Low-fima (75%) and DOX-only groups (50%). Echocardiography showed preserved left ventricular (LV) ejection fraction in the High-fima group, but not in the DOX-only group (P=0.002). LV dimensions increased in the DOX-only group; however, remodeling was attenuated in the Low-fima and High-fima groups. Hemodynamic assessment showed higher dP/dt in the High-fima group compared with the DOX-only group. A novel ARB, fimasartan, may prevent DOX-CMP and improve survival rate in a dose-dependent manner in a rat model of DOX-CMP and could be a treatment option for the prevention of DOX-CMP.
Angiotensin Receptor Antagonists/*therapeutic use ; Animals ; Biphenyl Compounds/*therapeutic use ; Cardiomyopathies/chemically induced/mortality/*prevention & control ; Doxorubicin/*toxicity ; Echocardiography ; Hemodynamics ; Pyrimidines/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1/chemistry/*metabolism ; Survival Rate ; Tetrazoles/*therapeutic use ; Ventricular Function, Left/physiology

OBJECTIVEThe beneficial effects of silymarin have been extensively studied in the context of inflammation and cancer treatment, yet much less is known about its therapeutic effect on diabetes. The present study was aimed to investigate the cytoprotective activity of silymarin against diabetes-induced cardiomyocyte apoptosis.

METHODSRats were randomly divided into: control group, untreated diabetes group and diabetes group treated with silymarin (120 mg/kg•d) for 10 d. Rats were sacrificed, and the cardiac muscle specimens and blood samples were collected. The immunoreactivity of caspase-3 and Bcl-2 in the cardiomyocytes was measured. Total proteins, glucose, insulin, creatinine, AST, ALT, cholesterol, and triglycerides levels were estimated.

RESULTSUnlike the treated diabetes group, cardiomyocyte apoptosis increased in the untreated rats, as evidenced by enhanced caspase-3 and declined Bcl-2 activities. The levels of glucose, creatinine, AST, ALT, cholesterol, and triglycerides declined in the treated rats. The declined levels of insulin were enhanced again after treatment of diabetic rats with silymarin, reflecting a restoration of the pancreatic β-cells activity.

CONCLUSIONThe findings of this study are of great importance, which confirmed for the first time that treatment of diabetic subjects with silymarin may protect cardiomyocytes against apoptosis and promote survival-restoration of the pancreatic β-cells.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Glucose ; Cholesterol ; blood ; Creatinine ; blood ; Diabetes Mellitus, Experimental ; complications ; Diabetic Cardiomyopathies ; prevention & control ; Heart ; drug effects ; Immunohistochemistry ; Insulin ; blood ; Male ; Myocardium ; pathology ; Myocytes, Cardiac ; drug effects ; Rats ; Silymarin ; pharmacology ; Triglycerides ; blood

Adult ; Cardiomyopathies ; epidemiology ; prevention & control ; Cardiomyopathy, Dilated ; epidemiology ; prevention & control ; Child ; China ; epidemiology ; Enterovirus Infections ; epidemiology ; prevention & control ; Environmental Monitoring ; Humans ; Male

Anthracyclines ; administration & dosage ; adverse effects ; Antineoplastic Agents ; administration & dosage ; adverse effects ; Biomarkers ; blood ; Cardiomyopathies ; chemically induced ; diagnosis ; prevention & control ; Cardiotonic Agents ; therapeutic use ; Child ; Child, Preschool ; Echocardiography ; Heart ; drug effects ; Heart Diseases ; chemically induced ; diagnosis ; prevention & control ; Humans ; Risk Factors ; Survival Analysis ; Troponin I ; analysis