Natural Compound Library Screening Identifies Oroxin A for the Treatment of Myocardial Ischemia/Reperfusion Injury
Xingdong Cheng1,2, Tingting Huang1, Chunhui Wang1
1Department of Anesthesiology, The Forth Affiliated Hospital of Anhui Medical University, Hefei, China.
Abstract:
Myocardial ischemia/reperfusion injury (MI/RI) is a serious pathophysiological process relating to cardiovascular disease. Oroxin A (OA) is a natural flavonoid glycoside with various biological activities. However, its effect on the pathophysiological process of MI/RI has not yet been reported. The aim of this study was to determine whether OA could alleviate MI/RI induced inflammation and pyroptosis in vivo and in vitro, providing a novel therapeutic regimen for the treatment of MI/RI. A high-throughput drug screening strategy was employed to test 2,661 natural compound libraries that can alleviate MI/RI in vivo and in vitro. The rat model of MI/RI was established by ligating the left anterior descending (LAD) coronary artery. H9c2 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to simulate MI/RI. The results show that OA is able to significantly inhibit apoptosis, pyroptosis and the inflammation response (TNF-α, IL-6, IL-8, IL-10, IL-1β, IL-18) in vivo and in vitro, and reduce the release of myocardial enzymes (cTnI, cTnT, CK-MB, LDH, AST). In the rat MI/RI model, OA can not only improve cardiac function and reduce inflammatory cell infiltration but also reduce myocardial infarct size. The results revealed that OA is an effective remedy against MI/RI as it reduces the inflammatory response and inhibits pyroptosis. This may provide a new therapeutic target for the clinical treatment of MI/RI.
Insights
Oroxin A (OA) effectively reduces inflammation and pyroptosis in myocardial ischemia/reperfusion injury (MI/RI). This natural compound improves cardiac function and may offer a novel therapeutic strategy for cardiovascular disease treatment.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Cellular Biology
Background:
- Myocardial ischemia/reperfusion injury (MI/RI) is a critical complication of cardiovascular disease.
- Oroxin A (OA), a natural flavonoid glycoside, possesses diverse biological activities.
- The therapeutic potential of OA in MI/RI remains unexplored.
Purpose of the Study:
- To investigate the protective effects of Oroxin A against MI/RI.
- To determine if OA can alleviate inflammation and pyroptosis in MI/RI.
- To explore OA as a potential therapeutic agent for MI/RI.
Main Methods:
- High-throughput screening of natural compounds.
- Establishment of a rat model for MI/RI (coronary artery ligation).
- In vitro simulation of MI/RI using H9c2 cells (oxygen-glucose deprivation/reperfusion).
Main Results:
- Oroxin A significantly inhibited apoptosis, pyroptosis, and inflammatory responses (e.g., TNF-α, IL-6, IL-1β) in vivo and in vitro.
- OA reduced the release of key myocardial enzymes (cTnI, cTnT, CK-MB, LDH, AST).
- In the rat model, OA improved cardiac function, reduced inflammatory cell infiltration, and decreased infarct size.
Conclusions:
- Oroxin A demonstrates significant efficacy in mitigating MI/RI.
- OA's mechanism involves reducing inflammation and inhibiting pyroptosis.
- OA presents a promising therapeutic target for clinical management of MI/RI.
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