Proteomics Revealed That Mitochondrial Function Contributed to the Protective Effect of Herba Siegesbeckiae Against Cardiac Ischemia/Reperfusion Injury

Xiaohong Wei; Yuzhuo Wu; Haie Pan; Qian Zhang; Ke He; Guiyang Xia; Huan Xia; Sheng Lin; Hong-Cai Shang

doi:10.3389/fcvm.2022.895797

Proteomics Revealed That Mitochondrial Function Contributed to the Protective Effect of Herba Siegesbeckiae Against Cardiac Ischemia/Reperfusion Injury

Front Cardiovasc Med. 2022 Jul 6:9:895797. doi: 10.3389/fcvm.2022.895797. eCollection 2022.

Authors

Xiaohong Wei^{1

2}, Yuzhuo Wu¹, Haie Pan¹, Qian Zhang¹, Ke He¹, Guiyang Xia¹, Huan Xia¹, Sheng Lin¹, Hong-Cai Shang¹

Affiliations

¹ Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
² Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Disease, Guangzhou, China.

Abstract

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.

Keywords: Herba Siegesbeckiae; MnSOD acetylation; NLRP3 inflammasome; mitochondrial electron transport chain; myocardial ischemia/reperfusion injury.