Acacetin alleviates myocardial ischaemia/reperfusion injury by inhibiting oxidative stress and apoptosis via the Nrf-2/HO-1 pathway

• Published in: Pharmaceutical biology 2022-12, Vol.60 (1), p.553-561
• Main Authors: Wu, Chan, Chen, Ruo-Lan, Wang, Yan, Wu, Wei-Yin, Li, Gang
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Arrhythmia; Bax; BAX protein; Bcl-2; Bcl-2 protein; bcl-2-Associated X Protein - metabolism; Cardiac arrhythmia; Collagen; Echocardiography; EKG; Fibrosis; Flavones - pharmacology; Flavonoids; GA-binding protein; Heart; Heme Oxygenase (Decyclizing) - metabolism; IL-6; Inflammation; Interleukin 10; Interleukin 6; Ischemia; Male; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - physiopathology; NF-E2-Related Factor 2 - metabolism; Oxidative stress; Oxidative Stress - drug effects; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Sprague-Dawley; Reperfusion; SOD1; TLR4; TLR4 protein; Toll-like receptors; Triphenyltetrazolium chloride; ventricular fibrillation; Ventricular premature; ventricular tachycardia; Western blotting
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2022.2041675

Acacetin is a natural source of flavonoids with anti-inflammatory and antioxidant effects. This study determines acacetin's protective effect and mechanism on myocardial ischaemia/reperfusion (I/R) injury. Sprague-Dawley rats were divided into sham and I/R injury and treatment with acacetin. Acacetin (10 mg/kg) was subcutaneously injected for 7 days. ECG and echocardiography were conducted to determine arrhythmia and heart function. The pathological characters of the heart were determined with triphenyl tetrazolium chloride staining, Haematoxylin & Eosin staining, and Masson staining. Expression of proteins in infarct tissues was examined with western blots. Administrated with acacetin in I/R rats significantly reduced the arrhythmia score from 4.90 to 2.50 and the reperfusion arrhythmia score from 3.79 to 1.82 in the vehicle or the acacetin group, respectively. LVEF was improved from 33.5% in the I/R group to 43.7% in the acacetin group, LVFS was increased from 16.4% to 24.5%, LVIDs was decreased from 6.5 to 5.3 mm. The inflammatory cell infiltration, myocardial fibrosis, and collagen 1 and 3 were reduced by acacetin. Acacetin promoted SOD and decreased MDA. In myocardial tissues, the expression level of TLR4 and IL-6 were restrained, and IL-10 was promoted. Apoptotic protein Bax was suppressed, and anti-apoptotic protein Bcl-2 was promoted in the acacetin group. Interestingly, the transcription factor Nrf-2/HO-1 pathway was also reversed by acacetin. Our findings indicated that acacetin has a potential therapeutic effect in clinical application on treating I/R-induced heart injury.