[Research progress on regulation of mitophagy by traditional Chinese medicine in prevention and treatment of chronic kidney diseases].

The prevalence of chronic kidney disease(CKD) increases year by year and has become a highly prevalent disease, seriously affecting the quality of life of patients and bringing heavy family burden. There are many diseases causing CKD, including va-rious primary and secondary glomerulonephritis, renal tubular injury, and renal vascular lesions. Although routine medical treatment for CKD can alleviate the clinical symptoms to a certain extent, it is sometimes difficult to prevent the progression of CKD. Traditional Chinese medicine(TCM) is advantageous in high safety, few adverse reactions, and definite clinical efficacy in the treatment of CKD. The active components contained can play a synergistic effect through multiple pathways and multiple targets to delay disease progression, but its mechanism of action has not been fully elucidated. As revealed by the literature in this field in China and abroad, abnormal mitophagy is a common feature of the pathogenesis of CKD of different types. In recent years, a large number of studies have proved that the regulation of mitophagy through the PINK1/Parkin signaling pathway and mitophagy receptor pathway could delay the progression of CKD and protect renal function. Therefore, the regulation of mitophagy by TCM in the prevention and treatment of CKD through related pathways has become a potential therapeutic target in recent years. This paper reviewed the research articles on the definite efficacy of TCM in preventing and treating CKD by regulating mitophagy through relevant pathways to provide new targets and stra-tegies for preventing and treating CKD and delaying their entry into end-stage renal diseases.

Preclinical study of Shen Qi Li Xin formula in improving the development of chronic heart failure.

Chronic heart failure (CHF) is a common clinical heart disease. In recent years, traditional Chinese medicines have shown good outcomes in CHF treatment. We aimed to explore the therapeutic effect of Shen Qi Li Xin formula (SQLXF) in CHF. CHF rats were treated with SQLXF at the doses of 8.48, 16.96, and 33.92 g/kg/d once a day for 4 weeks by intragastric administration. The hemodynamic and cardiac function parameters of the rats were monitored by conduction echocardiography. In our results, SQLXF treatment at the doses of 16.96 and 33.92 g/kg/d significantly improved the haemodynamics and cardiac function of CHF rats by enhancing the levels of LVSP, +dp/dtmax, -dp/dtmax, LVEF and LVFS and reducing the levels of LVEDP, LVEDD and LVESD. SQLXF treatment at 16.96 and 33.92 g/kg/d also attenuated the damage of myocardial tissues in CHF rats. In addition, compared with normal rats, the number of pericytes was reduced in myocardial tissues of CHF rats. SQLXF treatment at the doses of 16.96 and 33.92 g/kg/d obviously increased the number of pericytes and proliferation of endothelial cells and promoted angiogenesis in myocardial tissues of CHF rats. In vitro, SQLXF impaired low-oxygen-induced inhibition of cell viability and promotion of apoptosis in primary pericytes. Importantly, SQLXF enhanced the adhesion ability of pericytes to endothelial cells. In conclusion, SQLXF improved myocardial injury in CHF rats by enhancing the interaction between pericytes and endothelial cells, suggesting that SQLXF may be a potential drug for CHF treatment.

Shen Qi Li Xin formula improves chronic heart failure through balancing mitochondrial fission and fusion via upregulation of PGC-1α.

BACKGROUND: Our previous study proved that Shen Qi Li Xin formula (SQLXF) improved the heart function of chronic heart failure (CHF) patients, while the action mechanism remains unclear. METHODS: H&E staining and TUNEL staining were performed to measure myocardial damages. Western blot was used to examine the expression of proteins. Moreover, CCK-8 assay and flow cytometry were used to measure cell viability and cell apoptosis, respectively. Concentrations of ATP and ROS in cells, and mitochondrial membrane potential (MMP) were detected to estimate oxidative stress. RESULTS: In vivo, we found that SQLXF improved cardiac hemodynamic parameters, reduced LDH, CK-MB and BNP production, and attenuated myocardial damages in CHF rats. Besides, SQLXF promoted mitochondrial fusion-related proteins expression and inhibited fission-related proteins expression in CHF rats and oxygen glucose deprivation/reoxygenation (OGD/R)-induced cardiac myocytes (CMs). In vitro, our data show that certain dose of SQLXF inhibited OGD/R-induced CMs apoptosis, cell viability decreasing and oxidative stress. CONCLUSION: Overall, certain dose of SQLXF could effectively improve the cardiac function of CHF rats through inhibition of CMs apoptosis via balancing mitochondrial fission and fusion. Our data proved a novel action mechanism of SQLXF in CHF improvement, and provided a reference for clinical.

The role of Nrf2 in astragaloside IV-mediated antioxidative protection on heart failure.

CONTEXT: Heart failure is one of the most serious diseases worldwide. Astragaloside IV (ASI) is widely used in the treatment of cardiovascular diseases. OBJECTIVE: To elucidate the antioxidative mechanism of ASI in a rat model of left coronary artery ligation. MATERIALS AND METHODS: Left coronary artery of Sprague-Dawley rats was ligated to establish the model of heart failure, and then vehicle (saline) or ASI (1 mg/kg/day) was orally administered to the rats (n = 15) for 6 weeks. Echocardiography was used to evaluate the cardiac function. Myocardial infarct size was measured by triphenyltetrazolium chloride staining. Oxidative stress in the ventricular myocardium was determined. Molecular mechanisms were investigated by Western blot and chromatin immunoprecipitation. RESULTS: ASI improved the cardiac function, especially ejection fraction (75.27 ± 5.75% vs. 36.26 ± 4.14%) and fractional shortening (45.39 ± 3.66% vs. 17.88 ± 1.32%), and reduced the infarct size of left ventricle (20.69 ± 2.98% vs. 39.11 ± 3.97%). ASI maintained the levels of glutathione, catalase and superoxide dismutase and prevented the leakage of creatine kinase. In addition, ASI induced the protein expression of Nrf2 (1.97-fold) and HO-1 (2.79-fold), while reduced that of Keap-1 (0.77-fold) in the ventricular myocardium. In H9c2 cells, a rat cardiomyocyte cell line, ASI induced the translocation of Nrf2 from cytoplasm to nucleus, followed by transcriptional activation of NQO-1 (8.27-fold), SOD-2 (3.27-fold) and Txn-1 (9.83-fold) genes. DISCUSSION AND CONCLUSIONS: ASI prevented heart failure by counteracting oxidative stress through the Nrf2/HO-1 pathway. Application in clinical practice warrants further investigation.

Astragaloside IV alleviates heart failure by promoting angiogenesis through the JAK-STAT3 pathway.

CONTEXT: Heart failure (HF) is one of the most serious diseases worldwide. Astragaloside IV (ASI) is widely used for the treatment of cardiovascular disease in China. OBJECTIVE: To evaluate the protective effect of ASI on the HF in a Sprague-Dawley rat model of left coronary artery ligation, and investigate the angiogenesis-related mechanisms. MATERIALS AND METHODS: Left coronary artery was ligated to induce a rat model of HF, and the rats were treated with vehicle (saline) or different doses of ASI (0.1, 0.3 and 1 mg/kg/day) by oral gavage for 6 weeks. Cardiac function was evaluated by echocardiography. Infarct size was determined by triphenyltetrazolium chloride staining. Cardiac vascular density was analyzed by microangiography. Real-time PCR, Western blot and chromatin immunoprecipitation were performed to investigate the mechanisms. RESULTS: ASI treatment improved the body weight and survival rate of HF rats, as well as the cardiac function of HF rats, with significantly improved ejection fraction (75.27 ± 5.75% vs. 36.26 ± 4.14%) and fractional shortening (45.39 ± 3.66% vs. 17.88 ± 1.32%). ASI reduced the infarct size of the HF rats by 47%. ASI promoted angiogenesis, with increased vascular density (2.08-fold) and induced mRNA expression of CD31 (1.81-fold) and VEGF (2.70-fold) in the ischemic heart. Furthermore, ASI induced the phosphorylation of JAK (1.89-fold) and STAT3 (2.95-fold), as well as the activity of VEGF promoter which was regulated by STAT3. DISCUSSION AND CONCLUSIONS: ASI alleviated HF by promoting angiogenesis through JAK-STAT3 pathway, providing novel alternative strategies to prevent HF in the future.

A retrospective study of traditional Chinese medicine as an adjunctive therapy for patients with chronic heart failure.

This study retrospectively evaluated the effectiveness and safety of traditional Chinese medicine Shenqilixin Formula (SQLXF) as an adjunctive intervention for treating patients with chronic heart failure (CHF).This retrospective study included 135 patients with CHF. They were allocated to a treatment group or a control group according to the different treatments they received. Seventy five patients in the treatment group underwent SQLXF plus routine treatment, while 60 subjects in the control group received routine treatment only. The primary outcome was cardiac function. It was measured by the left ventricular end diastolic diameter (LVDD), left ventricular ejection fraction (LVEF), cardiac output (CO), every cardiac output (ECO), and cardiac index (CI). The secondary outcome included motor function. It was measured by the standard 6-MinuteWalk Test (6MWT). In addition, adverse events (AEs) were also recorded.Compared to subjects in the control group, patients in the treatment group revealed greater effectiveness in cardiac function, measured by LVEF (P < .05), CO (P < .05), and ECO (P < .05), and motor function, measured by the 6MWT scale (P < .05). Moreover, no significant differences of AEs were found between the 2 groups.SQLXF as an adjunctive therapy to routine treatment may help to improve both cardiac and motor function in patients with CHF.

[Effect of blood activating water relieving method on heart functions and serum levels of NT-proBNP in patients with heart failure with normal ejection fraction].

OBJECTIVE: To study the effect of blood activating water relieving method (BAWRM) on heart functions and serum levels of NT-proBNP in patients with heart failure with normal ejection fraction (HFNEF). METHODS: Sixty-four HFNEF patients were admitted to our hospital during January 2011 to June 2012. They were randomly assigned to the treatment group (32 cases) and the control group (32 cases). Patients in the control group received routine Western medical treatment, while those in the treatment group additionally took Chinese medical recipes for activating blood circulation and relieving water retention. Changes of Chinese medical syndromes, E/E', serum NT-proBNP contents were observed between the two groups. RESULTS: Compared with before treatment, their Chinese medical syndromes and E/E' were significantly improved, and serum NT-proBNP contents decreased in the two groups (P < 0.05). Compared with the control group, Chinese medical syndromes, E/E', serum NT-proBNP contents obviously decreased in the treatment group, showing statistical difference (P < 0.05). CONCLUSION: BAWRM was an effective way to improve the diastolic function of HFNEF patients and lower the serum level of NT-proBNP with confirmative efficacy.