Bellidifolin from Gentianella acuta (Michx.) Hulten protects H9c2 cells from hydrogen peroxide-induced injury via the PI3K-Akt signal pathway. (2022)

• Record Type: Journal Article
• Authors: Li, Siqi; Huang, Congying; Li, Xing; Meng, Xiangxi; Wen, Rong; Zhang, Xiaodong; Zhang, Chunhong; Li, Minhui
• Is Part Of: Toxicology reports. Volume 9(2022)
• Page Start: 1655
• Page End: 1665
• Publication Date: 2022
• Subjects: Bellidifolin -- Network pharmacology -- Liquid chromatography-mass spectrometry -- H2O2-induced injury -- Oxidative stress -- Protective effect; G. acuta Gentianella acuta(Michx.) Hulten -- H9c2 rat myocardial -- LDH lactate dehydrogenase -- CK creatine kinase -- ALT alanine aminotransferase -- SOD superoxide dismutase -- GSH-Px glutathione peroxidase -- GSK-3β glycogen synthase kinase-3β -- ROS reactive oxygen species -- PPI protein-protein interaction -- GO gene ontology -- PDB protein data bank -- KEGG kyoto encyclopedia of genes and genomes -- qRT-PCR quantitative reverse transcription PCR -- TP53 tumor protein P53 -- Akt1 protein kinase B1 -- TNF tumor necrosis factor -- VEGFA vascular endothelial growth factor A -- IL-6 interleukin 6 -- DEGs differentially expressed genes -- AMPK AMP-activated protein kinase -- cAMP cyclic adenosine monophosphate -- BP biological processes -- MF molecular functions -- CC cellular components; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2022.08.006
• Languages: English
• ISSNs: 2214-7500

Abstract

Abstract: Cardiovascular disease is the most common disease in the world and the first among the causes of human death. Its morbidity and mortality increase annually, but no effective treatment is available. Therefore, new drugs should be developed to treat cardiovascular disease. Gentianella acuta (Michx.) Hulten ( G. acuta ) is an important Mongolian medicine in China and elicits protective effects on cardiovascular health. In this study, liquid chromatography-mass spectrometry (LC-MS) combined with network pharmacology was used to screen the main active ingredients and confirm that bellidifolin was one of the main components for the treatment of ischemic heart disease. Then, rat myocardial (H9c2) cells injury model induced by hydrogen peroxide (H2 O2 ) in vitro was established to verify the effect of bellidifolin on oxidative stress stimulation, including determination of antioxidant enzyme activity and apoptosis. Transcriptome sequencing, qRT-PCR, and western blot were performed to further verify the antioxidant stress mechanism of bellidifolin. Results showed that bellidifolin pretreatment decreased the rate of apoptosis and the levels of lactate dehydrogenase (LDH), creatine kinase (CK), and alanine aminotransferase (ALT). Conversely, it increased the contents of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in a dose-dependent manner, indicating that bellidifolin caused a protective effect on cardiomyocyte injury. Bellidifolin minimized the H2 O2 -induced cell injury by activating the PI3K-Akt signal pathway and downregulating glycogen synthase kinase-3β (GSK-3β) and p-Akt1/Akt1. Therefore, this work revealed that G. acuta has a good development prospect as an edible medicinal plant in cardiovascular disease. Its bellidifolin component is a potential therapeutic agent for cardiovascular disease induced by oxidative stress damage. Graphical Abstract: ga1 Highlights: Tea made from G. acuta is consumed as a tonic for heart protection since a long time by the Ewenki population in Inner Mongolia. A variety of methods were used to study the mechanism of bellidifolin from G. acuta in the treatment of H2 O2 -induced cytotoxicity. The results demonstrate that PI3K-Akt signal pathway is the main pathway of bellidifolin in the treatment of H2 O2 -induced cytotoxicity.