2. Academic Validation
  3. Dl-3-n-butylphthalide attenuates acute myocardial infarction by inhibiting the binding of Nrf2/Keap1

Dl-3-n-butylphthalide attenuates acute myocardial infarction by inhibiting the binding of Nrf2/Keap1

  • Toxicol Appl Pharmacol. 2025 Sep:502:117424. doi: 10.1016/j.taap.2025.117424.
Yixiao Yan 1,  Zhiqiang Huang 1,  Linting Cheng 2,  Shengnan Zhao 1,  Haocheng Gao 1,  Kaifeng Chen 2,  Fulai Huang 2,  Lingyi Mou 2,  Gaozhi Chen 3,  Lili Fu 4,  Guolyu Xu 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China.
  • 2 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China.
  • 3 School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China. Electronic address: cgztc@163.com.
  • 4 School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China. Electronic address: 794096539@qq.com.
  • 5 School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China. Electronic address: xuguolv@126.com.
PMID: 40456322 DOI: 10.1016/j.taap.2025.117424
Abstract

Acute myocardial infarction (AMI) is a prevalent cardiovascular condition often encountered in clinics. It is characterized by an imbalance in the myocardial oxygen supply and demand and is thought to be associated to cell Apoptosis and oxidative stress. Dl-3-n-butylphthalide (NBP), a natural product extracted from celery for the clinical treatment of ischemic stroke, may mitigate the effects of myocardial infarction. To test this hypothesis, isoproterenol (ISO) which is a β-adrenoceptor agonist, was used to simulate the metabolic and morphological abnormalities of AMI. The results demonstrated that NBP significantly alleviated ISO-induced cardiac dysfunction, showing beneficial effects on cardiac inflammation, Apoptosis, fibrosis, and mitochondrial damage. Western blotting (WB), and qRT-PCR suggest that NBP may regulate the degradation of nuclear factor erythroid 2-related factor 2 (Nrf2). Further experiments revealed that NBP blocks the binding of Kelch-like ECH-associated protein-1 (Keap1) and Nrf2 and then inhibits the ubiquitination degradation of Nrf2. This study identifies NBP as a potent therapeutic agent for ISO-induced cardiac dysfunction by inhibiting Nrf2-Keap1 binding.

Keywords

Acute myocardial infarction (AMI); Dl-3-n-butylphthalide (NBP); Isoproterenol (ISO); Kelch-like ECH-associated protein-1 (Keap1); Nuclear factor erythroid2-related factor 2(Nrf2).

Figures
Products