Chaihujialonggumulitang shows psycho-cardiology therapeutic effect on acute myocardial infarction with comorbid anxiety by the activation of Nrf2/HO-1 pathway and suppression of oxidative stress and apoptosis

BACKGROUND: Anxiety is a common comorbidity of cardiovascular diseases, which deteriorated cardiac function. Chaihujialonggumulitang (BFG) was reported to have antioxidant properties, alleviate myocardial ischemia injury and improve anxiety-like behavior. The Nuclear factor erythroid 2-related factor 2 (Nrf2) /heme oxygenase-1 (HO-1) pathway is the main mechanism to defend against oxidative stress, and improve cardiac function. This study was to investigate the possible mechanism of BFG in the treatment of psycho-cardiology. METHODS: AMI with comorbid anxiety rat model was established by ligation of the left anterior descending coronary artery combined with uncertain empty bottle stimulation, followed by the administration of BFG (1 mL/100 g/d by gavage) or Dimethyl fumarate (DMF, 10 mg/kg/d by intraperitoneal injection) for 6 days. Echocardiography, myocardial injury markers, H&E, and Masson staining were employed to evaluate cardiac function. Behavioral tests and hippocampus neurotransmitters were applied to record anxiety-like behavior. We employed immunohistochemistry, RT-PCR, western blotting, and biochemical analysis to detect the protein and gene expression of Nrf2/HO-1 pathway-related factors, and oxidative stress and apoptosis parameters. RESULTS: Rats in the AMI and complex groups showed cardiac function deterioration, as well as anxiety-like behavior. BFG improved echocardiography indicators, reduced myocardial injury markers, and attenuated myocardial pathological changes. BFG also ameliorated anxiety-like behaviors and elevated neurotransmitters levels. BFG promoted the activation of Nrf2/HO-1 pathway, increased antioxidant enzyme activities, reduced lipid peroxidation levels, and alleviated oxidative damage and apoptosis. DMF showed therapeutic effects and molecular mechanisms similar to BFG. CONCLUSION: BFG may possess a psycho-cardiology therapeutic effect on AMI with comorbid anxiety by the activation of the Nrf2/HO-1 pathway and suppression of oxidative stress and apoptosis.