Carvacrol attenuated myocardial infarction through NLRP3-mediated pyroptosis and mTOR/Nrf2/PPARγ-dependent autophagic signaling.

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Tác giả: Faisal Albaqami, Hina Aslam, Najeeb Ur Rehman, Fawad Ali Shah

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : Toxicology and applied pharmacology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 685525

Myocardial ischemia, also known as myocardial infarction or heart attack, is a significant global health issue and a leading cause of mortality worldwide. The present study focuses on investigating the cardioprotective role of carvacrol on three specific pathways: nuclear factor E2-related factor (Nrf2) / peroxisome proliferator-activated receptor factor (PPARγ)-coupled anti-inflammatory response, inflammasome (NLRP3)-mediated pyroptosis, and mammalian target of rapamycin (mTOR)-dependent autophagic signaling. Male Sprague Dawley rats were divided into three experimental cohorts to determine the best dose for carvacrol (20 mg / kg, 50 mg / kg, and 80 mg/ kg) and the optimum treatment strategy. Our findings showed that isoproterenol raised the production of ROS, induced NLRP3-mediated pyroptosis, and modulated the mTOR-linked signaling cascade. Treatment with carvacrol activated the Nrf2 / HO-1 and PI3K / AKT signaling pathways that led to the reversal of NLRP3 inflammasome. Moreover, the Nrf2 inhibitor all-trans-retinoic acid (ATRA) antagonizes the protective effects of carvacrol and exacerbates myocardial infarction by inducing inflammatory mediators. Taken together, our findings suggest that carvacrol mitigated isoproterenol-induced myocardial ischemia, partially through the activation of Nrf2 and PPARγ and downregulation of NLRP3.
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