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

Abstract

BackgroundMyocardial 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 MethodsHerba 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.ResultsThe 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.ConclusionHerba 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.

D-β-Hydroxybutyrate Dehydrogenase Mitigates Diabetes-Induced Atherosclerosis through the Activation of Nrf2

“…can inhibit oxidative stress and subsequently resist damage due to cardiac ischemia/reperfusion by restoring mitochondrial ultrastructure and electron transport chain complex function through the upregulation of Bdh1 expression. 39 Xu et al found that the overexpression of Bdh1 could attenuate high-fat diet-induced liver damage by inhibiting oxidative stress and apoptosis. 40 Our results showed that Bdh1 overexpression reduced oxidative stress and inflammatory responses in macrophages and that AAV-mediated Bdh1 overexpression reduced vascular inflammatory responses.…”

Polyphenols as NLRP3 inflammasome modulators in cardiometabolic diseases: a review of in vivo studies

“…52 CVDs are the cardiometabolic alterations for which more in vivo studies have explored how polyphenols could modulate the NLRP3 inflammasome, with a total of 18 studies on the topic (17 preclinical and 1 clinical), whose main findings are summarized in Table 2. [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70] Regarding the pre-clinical trials, the two most commonly selected animal models corresponded to the middle cerebral artery occlusion/reperfusion model (MCAO/R) in rats 56,59,61,[64][65][66][67] and the myocardial ischemia/reperfusion model (MI/R) in rats or mice. 53,55,58,69,70 Other different…”

“…[53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70] Regarding the pre-clinical trials, the two most commonly selected animal models corresponded to the middle cerebral artery occlusion/reperfusion model (MCAO/R) in rats 56,59,61,[64][65][66][67] and the myocardial ischemia/reperfusion model (MI/R) in rats or mice. 53,55,58,69,70 Other different…”

“…Food & Function obtained from Abelmoschus manihot (L.) Medic and Herba Siegesbeckiae (both containing flavonoids compound) were tested, 69 as well as a Rhodiola crenulate extract containing salidroside, a phenylpropanoid. 62 The doses of supplementation used in the preclinical studies ranged from 1.0-320 mg kg −1 for pure compounds or a mix of them, 55,70 and 0.125-4.0 g kg −1 when extracts were used.…”

“…62 The doses of supplementation used in the preclinical studies ranged from 1.0-320 mg kg −1 for pure compounds or a mix of them, 55,70 and 0.125-4.0 g kg −1 when extracts were used. 62,69 The duration of the studies was different according to the model evaluated; for example, in those in which ischemia/reperfusion were induced the duration ranged from 15 min (ref. 58) to 7 days 55,69,70 prior to the induction process.…”