Related Experiment Video
Updated: Jul 17, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Targeting AMPK/eNOS pathway and mitochondria by sonlicromanol protects myocardial cells against ischemia-reperfusion
Kun Liao1, Fangfei Huang1, Xing Xie1
1Department of Cardiology, Affiliated Hospital of Xiangnan University, Chenzhou, China.
Abstract:
This work evaluated the cardioprotective effects of sonlicromanol, a new mitochondrial-directed drug, on cardiac ischemia/reperfusion (I/R) injury and explored the involvement of inflammatory and oxidative responses via activation of AMPK-eNOS-mitochondrial pathway. Male Sprague-Dawley rats underwent regional I/R injury through in vivo left anterior descending (LAD) coronary artery ligation for 40 minutes followed by 24 hours of reperfusion. Pretreatment of rats with sonlicromanol considerably reduced cardiac I/R injury in a dose-dependent manner, as indicated by lower infarct size and serum creatine-kinase levels, and improved cardiac function after reperfusion. Sonlicromanol (50 mg/kg) significantly reduced TNF-α, interleukin-1β, NF-κB-p65, and 8-isoprostane levels while increased manganese-superoxide dismutase and nitric-oxide levels and expression of eNOS and AMPK protein. It significantly reduced mitochondrial membrane depolarization and reactive oxygen species (ROS) levels. However, AMPK inhibition significantly reduced sonlicromanol protective actions. Cardioprotection by sonlicromanol was achieved by moderating inflammatory and oxidative responses, and AMPK/eNOS/mitochondrial signaling is a crucial regulator of these actions.
Insights
Sonlicromanol, a novel mitochondrial drug, protects the heart from ischemia/reperfusion injury by reducing inflammation and oxidative stress. This cardioprotective effect is mediated through the AMPK-eNOS-mitochondrial pathway.
Area of Science:
- Cardiovascular Pharmacology
- Mitochondrial Medicine
- Inflammation and Oxidative Stress Research
Background:
- Cardiac ischemia/reperfusion (I/R) injury remains a significant clinical challenge.
- Mitochondrial dysfunction and inflammatory/oxidative responses are key contributors to I/R injury.
- Novel therapeutic strategies targeting these pathways are urgently needed.
Purpose of the Study:
- To evaluate the cardioprotective effects of sonlicromanol, a mitochondrial-directed drug, against cardiac I/R injury.
- To investigate the role of inflammatory and oxidative responses in sonlicromanol's protective mechanism.
- To explore the involvement of the AMPK-eNOS-mitochondrial pathway in mediating these effects.
Main Methods:
- Regional I/R injury was induced in male Sprague-Dawley rats via LAD coronary artery ligation.
- Rats were pretreated with varying doses of sonlicromanol.
- Biochemical markers (infarct size, creatine kinase, inflammatory cytokines, oxidative stress markers), cardiac function, mitochondrial parameters, and protein expression (AMPK, eNOS) were assessed.
- The role of AMPK was confirmed using an AMPK inhibitor.
Main Results:
- Sonlicromanol significantly reduced infarct size, creatine kinase levels, and improved cardiac function post-I/R injury in a dose-dependent manner.
- Treatment with sonlicromanol decreased levels of TNF-α, IL-1β, NF-κB-p65, and 8-isoprostane, while increasing Mn-SOD and nitric oxide.
- Sonlicromanol reduced mitochondrial membrane depolarization and ROS production; these effects were blunted by AMPK inhibition.
Conclusions:
- Sonlicromanol exhibits significant cardioprotective effects against I/R injury.
- These protective effects are attributed to the moderation of inflammatory and oxidative responses.
- The AMPK/eNOS/mitochondrial signaling pathway is crucial for mediating sonlicromanol's cardioprotection.
