2. Academic Validation
  3. Calycosin alleviates myocardial fibrosis after myocardial infarction by restoring fatty acid metabolism homeostasis through inhibiting FAP

Calycosin alleviates myocardial fibrosis after myocardial infarction by restoring fatty acid metabolism homeostasis through inhibiting FAP

  • Phytomedicine. 2025 Sep:145:157045. doi: 10.1016/j.phymed.2025.157045.
Shu-Ning Sun 1,  Xin Liu 2,  Xing-Ling Chen 1,  Shu-Lin Liang 3,  Jin Li 1,  Hui-Li Liao 4,  Hong-Cheng Fang 5,  Shi-Hao Ni 1,  Yue Li 6,  Lu Lu 7,  Zhong-Qi Yang 8,  Hui Wu 9,  Ling-Jun Wang 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Traditional Chinese Medicine Syndrome, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangdong Provincial Clinical Research Academy of Chinese Medicine, Guangzhou 510407, China; Key Laboratory of Chronic Heart Failure, Guangzhou University of Chinese Medicine, Guangzhou 510407, China.
  • 2 State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, 510407, China; College of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510407, China.
  • 3 The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510407, China.
  • 4 The Geriatrics Department, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China.
  • 5 Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, 518104, China.
  • 6 Luohu District Traditional Chinese Medicine Hospital, Shenzhen 518001, China. Electronic address: yueli0419@163.com.
  • 7 State Key Laboratory of Traditional Chinese Medicine Syndrome, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangdong Provincial Clinical Research Academy of Chinese Medicine, Guangzhou 510407, China; Key Laboratory of Chronic Heart Failure, Guangzhou University of Chinese Medicine, Guangzhou 510407, China. Electronic address: coinland@gzucm.edu.cn.
  • 8 State Key Laboratory of Traditional Chinese Medicine Syndrome, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangdong Provincial Clinical Research Academy of Chinese Medicine, Guangzhou 510407, China; Key Laboratory of Chronic Heart Failure, Guangzhou University of Chinese Medicine, Guangzhou 510407, China. Electronic address: yang_zhongqi@163.com.
  • 9 State Key Laboratory of Traditional Chinese Medicine Syndrome, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangdong Provincial Clinical Research Academy of Chinese Medicine, Guangzhou 510407, China; Key Laboratory of Chronic Heart Failure, Guangzhou University of Chinese Medicine, Guangzhou 510407, China. Electronic address: wuhui026@126.com.
  • 10 State Key Laboratory of Traditional Chinese Medicine Syndrome, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangdong Provincial Clinical Research Academy of Chinese Medicine, Guangzhou 510407, China; Key Laboratory of Chronic Heart Failure, Guangzhou University of Chinese Medicine, Guangzhou 510407, China. Electronic address: smu868@gzucm.edu.cn.
PMID: 40627929 DOI: 10.1016/j.phymed.2025.157045
Abstract

Background: Myocardial fibrosis is a pivotal pathological mechanism underlying heart failure (HF) following myocardial infarction (MI). Natural herbal compounds exhibit great potential for anti-fibrotic applications, thereby warranting further in-depth investigation and development.

Objective: To find the critical gene characteristic of the early myocardial fibrosis following MI and identify the specifically targeted natural herbal compounds.

Methods: Through bioinformatics analysis and molecular phenotypic screening combined with various drug target validation methods, we sought to identify key fibrosis regulatory factors and related targeted natural herbal components. RNA-seq analysis was employed to explore potential downstream mechanisms. Both in vitro and in vivo experiments were conducted to evaluate the effects of FAP and Calycosin (CA) on fibrosis and lipid metabolism phenotypes in fibroblasts and cardiac tissues.

Results: RNA-Seq analysis revealed FAP as a core regulator of early post-MI fibrosis. CA, a natural herbal compound, could effectively inhibit FAP, thereby improving post-MI cardiac dysfunction via regulating FAP-mediated myocardial fibrosis. Further investigations demonstrated the pro-fibrotic efficacy of FAP may be closely related to its induction of lipid metabolic disorders. Correcting fatty acid (FA) metabolic disorders could abolish the pro-fibrotic effects of FAP. CA could ameliorate FA metabolic disorders in fibroblasts and cardiac tissues by inhibiting FAP. PPARα may be a downstream target of FAP to induce FA metabolic disorders, and CA could restore cardiac PPARα expression level by inhibiting FAP.

Conclusion: CA could alleviate post-MI myocardial fibrosis through inhibiting FAP, with the underlying mechanism involving the restoration of FA metabolism homeostasis by inhibiting FAP.

Keywords

Calycosin; FAP; Fatty acid metabolism; Myocardial fibrosis; PPARα.

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