Thymoquinone Protects Against Cardiac Hypertrophy via PPAR-γ/PI3K/Akt Pathway

  • J Cell Mol Med. 2026 Feb;30(3):e70911. doi: 10.1111/jcmm.70911.
Rong-Bin Qiu  1  2 ,  Zi-Ming Wu  1  2 ,  Zhi-Qiang Xu  1  2 ,  Li-Juan Hu  3 ,  Shi-Tao Zhao  1  2 ,  Rui-Yuan Zeng  1  2 ,  Zhi-Cong Qiu  1  2 ,  Lian-Fen Zhou  1  2 ,  Song-Qing Lai  1  2 ,  Wen-Jun Wang  1  2 ,  Li Wan  1  2
Affiliations
  • 1. Department of Cardiac Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 2. Institute of Cardiovascular Surgical Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 3. Gannan Health Vocational College, Ganzhou, China.
PMID: 41614426 DOI: 10.1111/jcmm.70911
Abstract

Thymoquinone (TQ), the principal active constituent of Nigella stativa, has demonstrated numerous biological properties and therapeutic effects on various diseases. However, its therapeutic potential against cardiac hypertrophy remains uncertain. This study aims to investigate the protective effects of TQ on stress-induced cardiac hypertrophy and elucidate the underlying mechanisms. Our findings reveal that TQ mitigates stress-induced cardiac hypertrophy in mice and AngII-induced hypertrophy in H9c2 cells. Moreover, TQ inhibits cardiomyocyte Ferroptosis and Apoptosis by downregulating PTGS2, Bax, and upregulating GPX4, Bcl-2, thereby alleviating cardiac hypertrophy and dysfunction. Mechanistically, the protective effects of TQ against Ferroptosis and Apoptosis in cardiac hypertrophy were reversed by the PPAR-γ inhibitor (GW9662). In addition, TQ treatment led to increased protein expression levels of P-PI3K and P-AKt. Taken together, our findings suggest that TQ could attenuate cardiac hypertrophy through activation of the PPAR-γ/PI3K/Akt signalling pathway.

Keywords
PI3K/Akt; PPAR‐γ; apoptosis; cardiac hypertrophy; ferroptosis; thymoquinone.
Products