郭彩霞
中国医学科学院阜外医院
ETHNOPHARMACOLOGICAL RELEVANCE:"Qi deficiency-blood stasis-water retention syndrome" was the most frequent syndrome among heart failure(HF) patients according to Traditional Chinese Medicine (TCM) theory. Xinfuli Granule (XG) was constructed on the basis of classical formula "Baoyuan decoction" to enhance the function of nourishing Qi, activating blood and removing water retention. XG treatment has obtained clinical effect on HF patients.AIM OF THE STUDY:The regulation of XG on energy metabolism of HF was investigated with special focus on endoplasmic reticulum stress (ERS) and mitochondrial function.MATERIALS AND METHODS:Components of XG was acquired by UPLC/Q-TOF-MS Analysis, left anterior descending ligation(LAD)-induced HF rats model and hypoxia-ischemia(H-I)-induced H9c2 cells model were constructed to evaluate the effect of XG treatment. Cardiac function was evaluated by echocardiographic parameters, energy metabolism was evaluated by metabolites and ATP/ADP/AMP levels in blood samples, cardiomyocyte morphology and myocardial fibrosis were assessed by HE staining and Masson staining, mitochondrial ultrastructure was observed under Transmission Electron Microscope, viability and apoptosis rate of H9c2 cells was detected by cell counting kit-8 reaction and flow cytometry analysis, respectively. Mitochondrial membrane potential (MMP) of H9c2 cells was observed by JC-1 kit under fluorescent microscope, expression of peroxisome-proliferator-activated receptor (PPAR)-coactivator (PGC1α), ERS-related genes and RHOA/ROCK pathway were analysed by Quantitative Real-time PCR (RT-qPCR) and Western Blot.RESULTS:Here, we showed that XG alleviated cardiac metabolic remodeling and stimulated ATP production through elevated expression of PGC1α in HF rats. XG also helped recover mitochondrial deformation and decrease apoptosis rate accompanied by an increase of the Bcl2/Bax ratio and the mitochondrial membrane potential in hypoxia-ischemia (H-I) H9c2 cells. In addition, we found that XG downregulated ERS-related proteins ATF4, CHOP, Phospho-eIF2α, and Phospho-PERK, and suppressed the RHOA/ROCK pathway, which served as a potential mediator of ERS.CONCLUSIONS:we found that XG improved energy production by alleviating mitochondrial injury and inhibiting ERS in heart failures mediated by the RHOA/ROCK pathway.
Journal of ethnopharmacology 2023
BACKGROUND:Chinese herbal medicine is widely used as a complement or alternative treatment in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) in China. We compared the incidence of the major adverse cardiovascular event (MACE) of CAD patients with or without the complement use of Chinese herbal medicine after PCI.METHODS:In this prospective, observational study that was conducted from September 2016 to August 2019 in Fuwai Hospital (China), we followed up consecutive patients who received PCI treatment for two years. MACE was defined as the composite all-cause mortality, revascularization, and myocardial infarction (MI) and was compared between those using (integrative medicine group) or those not using Chinese herbal medicine as an additional treatment to standard Western medicine, with unadjusted (Kaplan-Meier curves) and risk-adjusted (multivariable Cox regression) analyses.RESULTS:A total of 5942 patients after PCI were enrolled in this study, and 5453 patients were included in the final analysis (4189 [76.8%] male; mean age: 61.9 ± 9.9% years). During the follow-ups, 2932 (53.8%) patients used only Western medicine while 2521(46.2%) patients had used Chinese herbal medicine as an additional treatment to standard Western medicine. Patients in the integrative medicine group (IM group) were older than the Western medicine group (WM group), had more females and less previous MI. The incidence of MACE was 15.3% (449/2932) in WM group and 11.54% (291/2521) in IM group. Cox regression analysis showed that cumulative incidence of MACE was 27% lower in patients of the IM group than those in WM group (hazard ratio = 0.73; 95% CI: 0.63-0.85; P < 0.0001).CONCLUSIONS:For CAD patients after PCI treatment, complement use of Chinese herbal medicine is associated with a lower 2-year MACE incidence. Randomized prospective studies are warranted to provide higher levels of benefit evidence in these patients.
Journal of geriatric cardiology : JGC 2022
BACKGROUND:Qishen (QS) capsules, a Traditional Chinese Medicine, has been widely used to treat coronary heart disease in China. However, evidence of its effectiveness remains unclear.METHODS:To explore whether QS has cardioprotective efficacy and/or promotes angiogenesis after myocardial infarction (MI), we performed experiments in a preclinical rat MI model. One month after left anterior descending coronary artery ligation, the rats received either QS solution (0.4 g/kg/day) or the same volume of saline by intragastric injection for four weeks.RESULTS:Echocardiographic and hemodynamic analyses demonstrated relatively preserved cardiac function in MI rats administered QS. Indeed, QS treatment was associated with reduced infarct scar size and heart weight index, and these beneficial effects were responsible for enhancing angiogenesis. Mechanistically, QS treatment increased phosphorylation of protein kinase B (Akt) and downregulated phosphorylation of mitogen-activated protein kinase/extracellular-regulated kinase (MEK/ERK).CONCLUSIONS:QS therapy can improve the cardiac function of rats after MI by an underlying mechanism involving increased angiogenesis, at least partially via activation of the Akt signaling pathway and inhibition of MEK/ERK phosphorylation.
Journal of geriatric cardiology : JGC 2019
BACKGROUND:Recent clinical and experimental studies have confirmed the effects of Xinfuli Granule (XG), a compound Chinese medicine in the prevention and treatment of heart failure (HF). This study aimed to investigate the effects and the mechanisms of XG on ventricular reconstruction in rats with acute myocardial infarction (AMI).METHODS:Sprague-Dawley rats were subjected to left anterior descending branch ligation. The rats that survived 24 h were randomly assigned to five groups: medium-dose of XG group (MI+XGM), high-dose of XG group (MI+XGH), carvedilol group (MI+C), medium-dose of XG + carvedilol group (MI+C+XGM). Fourteen rats underwent identical surgical procedures without artery ligation, serving as sham controls. At 28 days, left ventricular weight to body weight (LVW/BW) and heart weight to body weight (HW/BW) were calculated; left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS), left ventricular internal diameter at systole (LVIDS) were measured by ultrasound; HE staining, Masson staining, and Sirius red staining were used to assess the myocardial pathological and physiological changes as well as myocardial fibrosis area and non-infarct zone I/III collagen ratio. Expression of Smad3 were detected and analyzed by Western blot, immunohistochemistry and immunofluorescence. P-Smad3, Smad2 and Smad7 in the TGF-β/Smads signaling pathway were also analyzed by Western blot.RESULTS:The LVIDS (P < 0.01), HW/BW (P < 0.05), type I/III collagen ratio (P < 0.01) and myocardial collagen (P < 0.01) decreased significantly while the LVW/BW, LVFS (P < 0.05) increased significantly in MI+XGM group as compared with those in other groups. The expression of key signal molecules of the TGF-β/Smads signaling pathway, including Smad3, P-Smad3 and Smad2 protein were decreased, while the expression of Smad7 increased in both XG and carvedilol treatment groups as compared to those of the MI group (all P < 0.01). Immunohistochemistry and immunofluorescence further confirmed the down-regulated Smad3 expression.CONCLUSION:XG can improve ventricular reconstruction and inhibit myocardial fibrosis in rats with AMI by regulating TGF-β/Smads signaling pathway.
Journal of geriatric cardiology : JGC 2017
BACKGROUND:Xinfuli Granule (XG), a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with doxorubicin-induced cardiotoxicity.METHODS:Sprague-Dawley rats were treated with intraperitoneal injection of Doxorubicin (DOX, 2.5 mg/kg per week) for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline (control group) or different dosage of XG (0.675 g/kg per day, 1.35 g/kg per day, and 2.7g/kg per day, respectively) for six weeks. Transthoracic echocardiography was performed to evaluate the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) before and after the XG treatment and histopathologic changes were also examined. Myocardial cell apoptosis was detected by TUNEL staining. The expression of related genes and proteins were analyzed using immunohistochemical staining.RESULTS:Compared to those in the control group, rats in XG treated groups showed significantly improved cardiac function and milder cardiac histopathological changes, lower cardiomyocyte apoptosis index, higher expression of Bcl-2 and lower expression of Bax.CONCLUSIONS:Administration of XG improves cardiac function and histopathological changes in rats with doxorubicin-induced cardiotoxicity. These effects are associated with inhibition of cardiomyocyte apoptosis, perhaps via regulation of Bcl-2 and Bax protein expression.
Journal of geriatric cardiology : JGC 2016
