2. Academic Validation
  3. Lycopene inhibits doxorubicin-induced heart failure by inhibiting ferroptosis through the Nrf2 signaling pathway

Lycopene inhibits doxorubicin-induced heart failure by inhibiting ferroptosis through the Nrf2 signaling pathway

  • Life Sci. 2025 Mar 15:365:123452. doi: 10.1016/j.lfs.2025.123452.
Rong Huang 1,  Chao Zhou 1,  Tianxiang Wang 1,  Yuanli Chen 1,  Zhouling Xie 1,  Lingling Wei 1,  Yajun Duan 2,  Chenzhong Liao 3,  Chuanrui Ma 4,  Xiaoxiao Yang 5
Affiliations

Affiliations

  • 1 Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, School of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • 2 Department of Cardiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  • 3 Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, School of Food and Biological Engineering, Hefei University of Technology, Hefei, China. Electronic address: czliao@hfut.edu.cn.
  • 4 First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China. Electronic address: chuanruima2013@mail.nankai.edu.cn.
  • 5 Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, School of Food and Biological Engineering, Hefei University of Technology, Hefei, China. Electronic address: yangxiaoxiao@hfut.edu.cn.
PMID: 39923835 DOI: 10.1016/j.lfs.2025.123452
Abstract

Aims: Lycopene (LYC) is a dietary nutrient that plays a protective role in various cardiovascular diseases. Doxorubicin (DOX)-induced cardiotoxicity is an important cause of poor prognosis in many Cancer patients treated with anthracyclines. This study aims to investigate the protective effects of LYC against DOX-induced heart failure (HF) and specific underlying mechanisms.

Materials and methods: DOX was used to establish HF model in cardiomyocytes and C57BL/6J mice to assess the protection of LYC against DOX-induced HF on inflammation, oxidative stress, and Ferroptosis.

Key findings: LYC ameliorated DOX-induced deterioration of cardiac function. Mechanistically, LYC reduced collagen content and fibrosis by inhibiting the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9. Additionally, LYC inhibited Reactive Oxygen Species (ROS) production by upregulating antioxidant Enzymes expression. LYC enhanced B-cell lymphoma 2 (Bcl-2), but reduced Apoptosis positive cells by reducing tumor protein 53 (p53), Bcl-2 associated X protein (Bax), and cleaved-Caspase 3 (c-Casp3) levels. Besides, LYC reduced inflammatory cytokine levels through activating peroxisome proliferator activated receptor gamma (PPARγ). Moreover, LYC ameliorated DOX-induced Ferroptosis both in vivo and in vitro. Furthermore, we showed that LYC inhibited DOX-induced Ferroptosis via binding to nuclear factor-erythroid 2-related factor 2 (Nrf2) to enhance its expression.

Significance: LYC improved DOX-induced cardiac dysfunction by reducing oxidative stress and inflammation, which was contributed by the reduction of Ferroptosis. At molecular levels, LYC ameliorated DOX-induced Ferroptosis through activating the Nrf2 signaling pathway. These findings indicate the potential of LYC as a therapeutic option for HF treatment.

Keywords

Ferroptosis; Heart failure; Inflammation; Lycopene; Nrf2; ROS.

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