Isoliquiritigenin Ameliorates Ischemia-Induced Myocardial Injury via Modulating the Nrf2/HO-1 Pathway in Mice

Abstract

Background Oxidative stress and inflammatory reaction play critical roles in acute myocardial infarction (AMI). Isoliquiritigenin (ISL), a flavonoid monomer extracted from licorice, has been found to have antioxidant and anti-inflammatory effects in cancer studies. Here, we tested the effect and underlying mechanisms of ISL on ischemia-induced myocardial injury in a mouse AMI model. Methods Adult C57BL/6 mice were pre-treated by intraperitoneal injection of ISL and/or a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor ML385 for 3 days, respectively. Then, the AMI model was established by ligating the anterior descending branch of the left coronary artery. Myocardial oxidative stress status, inflammatory response, cardiac function and infarction size were assessed after 7th day of surgery. Results Compared with sham group, the reactive oxygen species (ROS) and malondialdehyde (MDA) level in AMI group were significantly increased. However, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) level were dramatically decreased. ISL treatment significantly reduced the myocardial infarction area, improved cardiac function, inhibited the production of ROS and MDA and reduced the consumption of SOD and GSH-Px. Interestingly, ISL could significantly increase nuclear Nrf2 and cytosolic heme oxygenase 1 (HO-1) level in the infarcted myocardium and reduce the oxidative stress after AMI. Also, ISL treatment dramatically inhibited the activation of myocardial NF-κB pathway and reduced the expression of pro-inflammatory factors in the AMI group. However, the administration of ML385 not only suppressed the Nrf2/HO-1 activation, the anti-oxidant and anti-inflammatory effects induced by ISL, but also attenuated the beneficial role of ISL on reducing infarct size and improving cardiac function in the mouse with AMI. Conclusion The results suggested that activation of Nrf2/HO-1 pathway has an essential role in ISL-induced cardiac protection by alleviating myocardial oxidative stress and inflammation response in mice with AMI.

Inflammation and Oxidative Stress Role of S100A12 as a Potential Diagnostic and Therapeutic Biomarker in Acute Myocardial Infarction

“…In addition, the pathogenesis of AMI is associated with the excessive production of reactive oxygen species (ROS), which induce oxidative stress. Oxidative stress is the main cause of the poor prognosis of ischemic myocardial injury in AMI [ 17 ]. Several other studies have also identified oxidative stress as a key factor in AMI [ 18 – 20 ].…”

Porous magnetic Silica nanoparticles loaded with sulforaphane mitigate myocardial infarction injury through upregulating HSP70

“…However, this kind of pharmacological strategy requires su cient drug concentrations in the lesion, thus the drugs need to be administered before infarction. The MI mice were pre-treated by intraperitoneal injection of isoliquiritigenin for 3 days prior to the surgery to ameliorate MI injury [41]. Huoxin pill was administered via oral gavage prior to MI operation to prevent acute MI injury [42].…”

Activation of Nrf2 signaling: A key molecular mechanism of protection against cardiovascular diseases by natural products

“…In an LAD-induced MI model, isoliquiritigenin (ISL) or icariin significantly reduced the myocardial infarction area, improved cardiac function, inhibited ROS and MDA production, suppressed SOD and GPx consumption through increased nuclear Nrf2 and cytosolic HO-1 levels and reduced OS after AMI (Sai et al, 2022;D. Yao et al, 2022).…”

“…In an LAD-induced MI model, isoliquiritigenin (ISL) or icariin significantly reduced the myocardial infarction area, improved cardiac function, inhibited ROS and MDA production, suppressed SOD and GPx consumption through increased nuclear Nrf2 and cytosolic HO-1 levels and reduced OS after AMI ( Sai et al, 2022 ; D. Yao et al, 2022 ). Furthermore, in mice or rats with STZ-induced diabetes mellitus or high glucose-cultured H9c2, ISL attenuated inflammation and OS and protected against aortic injury through upregulation of Nrf2 and HO-1 (X.…”