Supplementary file 2_Poge heart-saving decoction meliorates heart failure by suppressing apoptosis and fibrosis via regulation of the PI3K/AKT pathway.docx

BackgroundPoge Heart-Saving Decoction (PHSD) is a traditional Chinese medicine formulation that has been used clinically for decades in the treatment of heart failure (HF). However, its precise therapeutic mechanisms remain incompletely understood.
MethodsThe metabolites of PHSD were characterized using UHPLC-MS/MS. Network analysis was subsequently employed to identify the mechanism. A mouse model of HF was established through intraperitoneal injection of isoproterenol (ISO), followed by treatment with PHSD at low, medium or high doses. Cardiac function parameters were evaluated by echocardiography, and NT-proBNP levels were measured. Histopathological examination of myocardial tissue was conducted, complemented by analyses of protein and mRNA expression levels related to apoptosis and fibrosis targeting the PI3K/AKT pathway.
ResultsA total of 133 metabolites in PHSD were identified. Network analysis suggested that PHSD may ameliorate HF by targeting key proteins such as AKT1, TNF, and BCL-2. In vivo experiments demonstrated that PHSD alleviated ISO-induced myocardial apoptosis by balanced BAX and BCL-2. Furthermore, PHSD significantly reduced the deposition of Collagen I and Collagen III and markedly downregulated the expression of PI3K and AKT.
ConclusionOur study demonstrated that PHSD ameliorates HF by suppressing myocardial apoptosis and fibrosis through inhibition of the PI3K/AKT pathway. These findings indicate that PHSD is a prospective therapeutic agent against HF.