Thymoquinone and aerobic exercise mitigate HFpEF-induced cardiac injury via Apaf1/Cycs axis regulation
Year: 2025
Type: article
Abstract: Introduction Heart failure with preserved ejection fraction (HFpEF) is a prevalent clinical syndrome associated with high morbidity and mortality. Oxidative stress, apoptosis, and fibrosis are central to its pathophysiology. This study aimed to investigate the synergistic cardioprotective effects of thymoquinone (TQ) and aerobic exercise, with a particular focus on the Apaf1/Cycs-mediated apoptotic pathway. Methods Male C57BL/6J mice were randomly assigned to five groups: Control, HFpEF, HFpEF + TQ, HFpEF + exercise, and HFpEF + TQ + exercise. HFpEF was induced by a high-fat diet combined with Nω-Nitro-L-arginine methyl ester (L-NAME) administration for 10 weeks. TQ (50 mg/kg/day) and aerobic exercise (60% of maximal velocity, 5 days/week for 12 weeks) were applied as interventions. In vitro HFpEF models were established in H9c2 cardiomyoblast cells treated with L-NAME. Histological and molecular changes were assessed by immunofluorescence, co-immunoprecipitation, and TUNEL assays. Results The combined treatment of TQ and aerobic exercise significantly reduced myocardial fibrosis, apoptosis, and oxidative stress compared with either intervention alone. Mechanistically, the combination downregulated the interaction between Apaf1 and Cycs, thereby suppressing cardiomyocyte apoptosis. Discussion These findings demonstrate that TQ and aerobic exercise exert synergistic cardioprotective effects in HFpEF by attenuating oxidative stress, fibrosis, and apoptosis through inhibition of the Apaf1/Cycs apoptotic pathway. The results provide new insights into adjunctive therapeutic strategies for HFpEF management.
Source: Frontiers in Pharmacology
Authors: Zuowei Pei, Shan Gao, Jin Yang, Chang Liu, Yanyan Pan
Institution: Dalian University of Technology
Language: English
Subfield: Complementary and alternative medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funder: Dalian University of Technology
OpenAlex ID: W4414972502