Aconiti Lateralis Radix Praeparata ameliorates heart failure via PI3K/AKT/Bnip3 pathway

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

Background Chronic heart failure (CHF) is one of the leading causes high mortality worldwide. It characterized by pathological hypertrophy and poses a major threat to human health. Aconiti Lateralis Radix Praeparata widely used in ancient China treat CHF. However, pathology obscured, necessitating further exploration. Methods Prospective targets were predicted network analysis. A transverse aortic constriction (TAC) mice model was subsequently constructed determine effects aqueous extract (AEA) on The echocardiography performed investigate cardiac function. Histopathological analysis tissue conducted assess myocardial fibrosis. Nontargeted metabolomics analyze serum metabolites. phosphorylation level PI3K AKT, downstream such as Bnip3, p62, Atg5, LC3II measured Western blotting. In vitro , norepinephrine (NE) stimulate hypertrophy. Parameters reactive oxygen species levels, mitochondrial membrane potential, ATP concentration, CK/MB content detected H9c2 cells. Results AEA significantly alleviated Network indicated participation AKT CHF, modulated Praeparata. vivo administration effectively ameliorated performance, evidenced elevation ejection fraction. displayed diminishment collagen fiber. Metabolomics showed that several metabolites tetrahydroxycorticosterone, decylubiquinone taurocholic acid increased TAC serum. Additionally, levels expression Drp1, Opa1, Atg5 altered group. NE stimulation cell surface area deteriorated functions partially reversed results, mechanism associated with mitophagy. Conclusion This study revealed improved function via PI3K/AKT/Bnip3 pathway.

Language: Английский

Ginseng Radix et Rhizoma enhanced the effect of metoprolol in chronic heart failure by inhibiting autophagy in male C57BL/6J mice

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(8), P. e0301875 - e0301875

Published: Aug. 14, 2024

Background Ginseng Radix et Rhizoma (GS) is frequently used as an adjuvant therapy for patients with heart failure (HF). Metoprolol widely in HF. However, there no report on the combined effects of GS and metoprolol Objective This study investigated male C57BL/6J mice HF underlying mechanisms. Materials methods We utilized a mouse myocardial model to measure serum levels creatine kinase (CK) kinase-MB form (CK-MB) using automated biochemical analyzer. Lactate dehydrogenase (LDH) cardiac troponin (cTnT) were determined enzyme-linked immunosorbent assays. Autophagy cells was evaluated transmission electron microscopy, changes signal pathway proteins related autophagy analyzed by Western blotting. Results improved function, reduced damage, decreased CK, CK-MB, LDH, cTnT. The combination reducing autophagy-related (LC3, p62, Beclin1, Atg5) increasing ratios p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR. Conclusion enhanced anti-heart effect metoprolol. Its mechanism action might be inhibition mediated activation PI3K/Akt/mTOR pathway.

Language: Английский