ABSTRACT
BACKGROUND: Ginseng Radix et Rhizoma (GS) is frequently used as an adjuvant therapy for patients with heart failure (HF). Metoprolol is widely used in patients with HF. However, there is no report on the combined effects of GS and metoprolol in patients with HF. OBJECTIVE: This study investigated the combined effects of GS and metoprolol in male C57BL/6J mice with HF and the underlying mechanisms. MATERIALS AND METHODS: We utilized a mouse myocardial HF model to measure the serum levels of creatine kinase (CK) and creatine kinase-MB form (CK-MB) using an automated biochemical analyzer. Lactate dehydrogenase (LDH) and cardiac troponin (cTnT) levels were determined using enzyme-linked immunosorbent assays. Autophagy of myocardial cells was evaluated using transmission electron microscopy, and changes in signal pathway proteins related to autophagy were analyzed by Western blotting. RESULTS: GS combined with metoprolol improved heart function, reduced heart damage, and decreased serum levels of CK, CK-MB, LDH, and cTnT. The combination of GS and metoprolol decreased autophagy in myocardial cells by reducing the levels of autophagy-related proteins (LC3, p62, Beclin1, and Atg5) and increasing the ratios of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR. CONCLUSION: GS enhanced the anti-heart failure effect of metoprolol. Its mechanism of action might be related to the inhibition of autophagy mediated by the activation of the PI3K/Akt/mTOR pathway.
Subject(s)
Autophagy , Heart Failure , Metoprolol , Mice, Inbred C57BL , Panax , Animals , Male , Autophagy/drug effects , Heart Failure/drug therapy , Heart Failure/pathology , Heart Failure/metabolism , Metoprolol/pharmacology , Mice , Panax/chemistry , Signal Transduction/drug effects , Chronic Disease , Rhizome/chemistry , Disease Models, Animal , L-Lactate Dehydrogenase/blood , L-Lactate Dehydrogenase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Plant Extracts/pharmacology , Creatine Kinase/blood , Drug Synergism , Creatine Kinase, MB Form/bloodABSTRACT
Objective: To explain the "multi-components, multi-targets, multi-pathways" mechanism of Erzhiwan in treating benign prostatic hyperplasia(BPH) based the network pharmacology. Method: Ingenuity pathway analysis(IPA) was used to construct components-targets-diseases network and PPI network, then the classified enrichment analysis of gene ontology (GO) and pathway enrichment analysis (KEGG) were carried out on the main function of its gene sets, so as to discuss the mechanism of Erzhiwan in the treatment of BPH. Result: Erzhiwan has 19 components in IPA; and apigenin,luteolin,oleanolic acid and quercitrin were common components of Ligustri Lucidi Fructus and Echiptae Herba and the main component of Erzhiwan. Muscarinic acetylcholine receptor M3 (CHRM3), muscarinic acetylcholine receptor M2 (CHRM2), urokinase plasminogen activator receptor (PLAUR), kinin releasing enzyme 3 (KLK3), cadherin 1 (CDH1), chemokines 3 (CCL3) and metalloproteinase-1 (MMP-1) were important targets for Erzhiwan to treat BPH. The target proteins in PPI network were enriched with 20 GO functions and 5 main KEGG pathways, and Docking was verified for relevant targets. Conclusion: Erzhiwan may play a role in treating BPH by activating MMP-1 and inhibiting KLK3 and CCL3 protein expressions, inducing apoptosis, inhibiting cell proliferation and intervening relevant pathways of mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK) and nuclear factor(NF)-κB(NF-κB).