Annals of clinical and laboratory science · 2025
Auraptene Regulates Endoplasmic Reticulum Stress through the EGFR/ERK Signaling Pathway to Improve Acute Myocardial Infarction Outcome.
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Jin Shuang, Zhang Tianjie
Аннотация
OBJECTIVE: The mechanism of auraptene (AUR) in the treatment of acute myocardial infarction (AMI) was explored through in vitro and in vivo experiments combined with network pharmacology technology.
METHODS: Network pharmacology and molecular docking were used to predict the potential targets and related pathways of AUR in AMI. AMI was induced by ligating the left anterior descending coronary artery of Sprague-Dawley rats. Prior to modeling, AUR (50 mg/kg) was administered continuously for one week. AMI in rats was assessed by ultrasonic electrocardiogram, TTC staining, serum myocardial enzyme, hematoxylin-eosin staining, TUNEL staining, and apoptotic protein detection. Endoplasmic reticulum stress (ERS) in rat myocardium was evaluated by dihydroethidium staining and measurement of ERS-related proteins. An AMI cell model was established in oxygen and glucose deprivation (OGD)-induced H9C2 rat cardiomyocytes. Interventions with AUR, ERS agonist tunicamycin (TM), or epithelial growth factor (EGF) (EGFR agonist) were applied to H9C2 cells induced by OGD. Cell damage was evaluated using CCK-8 assay, lactic dehydrogenase measurement, and apoptotic protein detection. ERS in H9C2 cells was evaluated using the ER-Tracker Red molecular probe and ERS-labeled proteins. The expression of EGFR/extracellular regulated protein kinases (ERK) signaling pathway-related proteins was detected by western blot.
RESULTS: Network pharmacology and molecular docking suggest that EGFR may be a potential target for AUR in AMI, with the ERK signaling pathway identified as a crucial pathway. In vivo, AUR preconditioning significantly improved myocardial injury in AMI rats and inhibited ERS and EGFR/ERK signaling pathway activities in myocardial tissue. In vitro, AUR pretreatment reduced ERS induced by OGD in H9C2 cells. Compared to the OGD+AUR group, the OGD+AUR+TM group showed significantly increased cell damage and ERS level (P<0.05). Compared with the OGD+AUR group, the activity of the EGFR/ERK signaling pathway, ERS level, and the degree of cell damage in the OGD+AUR+EGF group were significantly improved (P<0.01).
CONCLUSION: AUR inhibits ERS by regulating the EGFR/ERK signaling pathway, thus improving outcomes in AMI rats.
METHODS: Network pharmacology and molecular docking were used to predict the potential targets and related pathways of AUR in AMI. AMI was induced by ligating the left anterior descending coronary artery of Sprague-Dawley rats. Prior to modeling, AUR (50 mg/kg) was administered continuously for one week. AMI in rats was assessed by ultrasonic electrocardiogram, TTC staining, serum myocardial enzyme, hematoxylin-eosin staining, TUNEL staining, and apoptotic protein detection. Endoplasmic reticulum stress (ERS) in rat myocardium was evaluated by dihydroethidium staining and measurement of ERS-related proteins. An AMI cell model was established in oxygen and glucose deprivation (OGD)-induced H9C2 rat cardiomyocytes. Interventions with AUR, ERS agonist tunicamycin (TM), or epithelial growth factor (EGF) (EGFR agonist) were applied to H9C2 cells induced by OGD. Cell damage was evaluated using CCK-8 assay, lactic dehydrogenase measurement, and apoptotic protein detection. ERS in H9C2 cells was evaluated using the ER-Tracker Red molecular probe and ERS-labeled proteins. The expression of EGFR/extracellular regulated protein kinases (ERK) signaling pathway-related proteins was detected by western blot.
RESULTS: Network pharmacology and molecular docking suggest that EGFR may be a potential target for AUR in AMI, with the ERK signaling pathway identified as a crucial pathway. In vivo, AUR preconditioning significantly improved myocardial injury in AMI rats and inhibited ERS and EGFR/ERK signaling pathway activities in myocardial tissue. In vitro, AUR pretreatment reduced ERS induced by OGD in H9C2 cells. Compared to the OGD+AUR group, the OGD+AUR+TM group showed significantly increased cell damage and ERS level (P<0.05). Compared with the OGD+AUR group, the activity of the EGFR/ERK signaling pathway, ERS level, and the degree of cell damage in the OGD+AUR+EGF group were significantly improved (P<0.01).
CONCLUSION: AUR inhibits ERS by regulating the EGFR/ERK signaling pathway, thus improving outcomes in AMI rats.