2. Academic Validation
  3. Bellidifolin ameliorates isoprenaline-induced cardiac hypertrophy by the Nox4/ROS signalling pathway through inhibiting BRD4

Bellidifolin ameliorates isoprenaline-induced cardiac hypertrophy by the Nox4/ROS signalling pathway through inhibiting BRD4

  • Cell Death Discov. 2023 Aug 1;9(1):279. doi: 10.1038/s41420-023-01563-2.
Dingyan Zhou # 1,  Weizhe Liu # 1 2,  Juanjuan Zhang # 1 3,  Yucui Dong 1,  Jiangli Wu 4,  Yu Zhang 1,  Cheng Dai 1,  Tingting Zhang 1,  Gaoshan Yang 1 2 3,  Yue Zhang 5 6 7,  Aiying Li 8 9 10
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China.
  • 2 Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation, Shijiazhuang, China.
  • 3 Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang, China.
  • 4 Department of Technology, Hebei University of Chinese Medicine, Shijiazhuang, China.
  • 5 Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China. yuezhang0311@outlook.com.
  • 6 Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation, Shijiazhuang, China. yuezhang0311@outlook.com.
  • 7 Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang, China. yuezhang0311@outlook.com.
  • 8 Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China. aiyingli1963@163.com.
  • 9 Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation, Shijiazhuang, China. aiyingli1963@163.com.
  • 10 Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang, China. aiyingli1963@163.com.
  • # Contributed equally.
PMID: 37528096 DOI: 10.1038/s41420-023-01563-2
Abstract

To date, there is no effective therapy for pathological cardiac hypertrophy, which can ultimately lead to heart failure. Bellidifolin (BEL) is an active xanthone component of Gentianella acuta (G. acuta) with a protective function for the heart. However, the role and mechanism of BEL action in cardiac hypertrophy remain unknown. In this study, the mouse model of cardiac hypertrophy was established by isoprenaline (ISO) induction with or without BEL treatment. The results showed that BEL alleviated cardiac dysfunction and pathological changes induced by ISO in the mice. The expression of cardiac hypertrophy marker genes, including ANP, BNP, and β-MHC, were inhibited by BEL both in mice and in H9C2 cells. Furthermore, BEL repressed the epigenetic regulator bromodomain-containing protein 4 (BRD4) to reduce the ISO-induced acetylation of H3K122 and phosphorylation of RNA Pol II. The NOX4/ROS/ADAM17 signalling pathway was also inhibited by BEL in a BRD4 dependent manner. Thus, BEL alleviated cardiac hypertrophy and cardiac dysfunction via the BRD4/NOX4/ROS axes during ISO-induced cardiac hypertrophy. These findings clarify the function and molecular mechanism of BEL action in the therapeutic intervention of cardiac hypertrophy.

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