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Published on: July 13, 2018
Proteomics Revealed That Mitochondrial Function Contributed to the Protective Effect of Herba Siegesbeckiae Against
Xiaohong Wei1,2, Yuzhuo Wu1, Haie Pan1
1Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Insights
Herba Siegesbeckiae aqueous extract effectively treats myocardial ischemia/reperfusion injury by reducing oxidative stress and inflammation. This traditional herb protects the heart by restoring mitochondrial function and regulating key protein expressions.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Myocardial ischemia/reperfusion (I/R) injury poses a significant clinical challenge, particularly during percutaneous coronary intervention, with limited therapeutic options.
- Herba Siegesbeckiae (HS), a traditional herb, exhibits known cardiovascular protective effects, yet its specific role in cardiac I/R injury remains under-investigated.
Purpose of the Study:
- To investigate the therapeutic effects of Herba Siegesbeckiae aqueous extract on cardiac I/R injury.
- To elucidate the underlying molecular mechanisms by which HS mitigates I/R-induced damage.
Main Methods:
- Preparation and chemical analysis (UHPLC-MS/MS) of Herba Siegesbeckiae aqueous extract.
- Induction of I/R injury in Sprague-Dawley rats via coronary artery occlusion and reperfusion.
- Comprehensive evaluation of cardiac function, histology, biochemistry, proteomics, mitochondrial function, oxidative stress markers, and inflammasome activity.
Main Results:
- HS extract significantly reduced infarct size, apoptosis, and cardiac enzyme levels, improving ECG and hemodynamic parameters.
- Proteomic analysis revealed HS modulated the expression of key proteins including Adgb, Cbr1, and COX7A.
- HS preserved mitochondrial ultrastructure and electron transport chain function, suppressed oxidative stress (ROS, RNS), and inhibited NLRP3 inflammasome activation and pyroptosis.
Conclusions:
- Herba Siegesbeckiae aqueous extract demonstrates significant cardioprotective effects against I/R injury.
- The protective mechanisms involve mitigating oxidative stress, inhibiting NLRP3 inflammasome, and restoring mitochondrial function.
- HS regulates specific protein expressions, offering a promising therapeutic strategy for cardiac I/R injury.
Background:
Myocardial ischemia/reperfusion (I/R) injury is the main obstacle to percutaneous coronary intervention, lacking effective therapeutic measures in a clinical setting. Herba Siegesbeckiae (HS) is a traditional herb with multiple pharmacological activities and evidence of cardiovascular protection. However, few data are available regarding the role of HS in cardiac I/R. This study aimed to explore the effect and underlying mechanism of HS aqueous extract on cardiac I/R injury.
Materials And Methods:
Herba Siegesbeckiae aqueous extract was prepared and analyzed by UHPLC-MS/MS. After intragastric administration of HS once daily for 7 days, male Sprague-Dawley rats were subjected to 30 min occlusion of the left anterior descending coronary artery followed by 120 min reperfusion to elicit I/R. Various parameters like myocardial infarction and apoptosis, 12-lead ECG and hemodynamics, cardiac morphology and myocardial enzymes, quantitative proteomics, mitochondrial ultrastructure and electron transport chain (ETC) function, oxidative stress and antioxidation, and NLRP3 inflammasome and inflammation were evaluated.
Results:
The chemical constituents of HS aqueous extract were mainly divided into flavonoids, diterpenoids, and organic acids. In vivo, HS aqueous extract notably alleviated myocardial I/R injury, as evidenced by a reduction in infarct size, apoptotic cells, and cardiac lesion enzymes; decline of ST-segment elevation; improvement of cardiac function; and preservation of morphology. Quantitative proteomics demonstrated that HS reversed the alteration in the expression of Adgb, Cbr1, Decr1, Eif5, Uchl5, Lmo7, Bdh1, Ckmt2, COX7A, and RT1-CE1 after I/R. In addition, HS preserved myocardial ultrastructure and restored the function of mitochondrial ETC complexes following exposure to I/R; HS significantly suppressed I/R-elicited increase of ROS, RNS, MDA, and 8-OHdG, restrained the acetylation of MnSOD, and recovered the activity of MnSOD; and HS reversed I/R-induced elevation of NLRP3 inflammasome and inhibited the release of inflammatory factors and pyroptosis.
Conclusion:
Herba Siegesbeckiae aqueous extract ameliorated cardiac I/R injury, which is associated with mitigating oxidative stress, suppressing NLRP3 inflammasome, and restoring mitochondrial function by regulating the expression of Adgb, Cbr1, Decr1, Eif5, Uchl5, Lmo7, Bdh1, Ckmt2, COX7A, and RT1-CE1.
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