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

Pharm Biol. 2022 Dec;60(1):553-561. doi: 10.1080/13880209.2022.2041675.

Abstract

Context: Acacetin is a natural source of flavonoids with anti-inflammatory and antioxidant effects.

Objective: This study determines acacetin's protective effect and mechanism on myocardial ischaemia/reperfusion (I/R) injury.

Materials and methods: 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.

Results: 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.

Discussion and conclusion: Our findings indicated that acacetin has a potential therapeutic effect in clinical application on treating I/R-induced heart injury.

Keywords: Bax; Bcl-2; IL-6; SOD1; TLR4; Ventricular premature; collagen; inflammation; ventricular fibrillation; ventricular tachycardia.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Flavones / pharmacology*
  • Heme Oxygenase (Decyclizing) / metabolism
  • Male
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / physiopathology
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Bax protein, rat
  • Bcl2 protein, rat
  • Flavones
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • acacetin

Grants and funding

This study was supported by the National Natural Science Foundation of China (Grant No. 81900336 and 81970283) and a Joint Fund across the Taiwan Straits from the National Natural Science Foundation of China (Grant No. U1605226), a Science and Technology Project from Xiamen Science and Technology Bureau, Fujian Province, China (Grant Nos. 3502Z20184025 and 3502Z20184024).