2. Academic Validation
  3. Chlorogenic acid attenuates pyrrolizidine alkaloid-induced liver injury through modulation of the SIRT1/FXR signaling pathway

Chlorogenic acid attenuates pyrrolizidine alkaloid-induced liver injury through modulation of the SIRT1/FXR signaling pathway

  • Chin Med. 2025 Mar 12;20(1):34. doi: 10.1186/s13020-025-01077-2.
Jie Xu # 1 2,  Qiongwen Xue # 1 3,  Aizhen Xiong 1 3,  Yilin Chen 1 3,  Xunjiang Wang 1 3,  Xing Yan 1 3,  Deqing Ruan 1 3,  Yumeng Zhang 1 3,  Zhengtao Wang 1 3,  Lili Ding 4 5,  Li Yang 6 7
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Complex Prescriptions, The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 2 Department of Pharmacy, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China.
  • 3 State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 4 Shanghai Key Laboratory of Complex Prescriptions, The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. nail8219@126.com.
  • 5 State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. nail8219@126.com.
  • 6 Shanghai Key Laboratory of Complex Prescriptions, The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. yangli7951@hotmail.com.
  • 7 State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. yangli7951@hotmail.com.
  • # Contributed equally.
PMID: 40069808 DOI: 10.1186/s13020-025-01077-2
Abstract

Background: Pyrrolizidine Alkaloids (PAs), recognized globally for their hepatotoxic properties, significantly contribute to liver damage through an imbalance in bile acid homeostasis. Addressing this imbalance is crucial for therapeutic interventions in PA-related liver injuries. Chlorogenic acid (Cga), a phenolic compound derived from medicinal Plants, has demonstrated hepato-protective effects across a spectrum of liver disorders. The specific influence and underlying mechanisms by which Cga mitigates PA-induced liver damage have not been clearly defined.

Materials and methods: To explore the protective effects of Cga against acute PA toxicity, a murine model was established. The influence of Cga on bile acid metabolism was confirmed through a variety of Molecular Biology techniques. These included RNA Sequencing, western blotting, and immunoprecipitation, along with quantitative analyses of bile acid concentrations.

Results: Our findings indicate that Cga enhances Sirtuin 1 (SIRT1) activation and increases farnesoid X receptor (FXR) signaling, which are crucial for maintaining bile acid balance in PA-induced hepatic injury. When mice subjected to PA-induced hepatic injury were treated with SIRT1 inhibitors alongside Cga, the hepatoprotective effects of Cga were significantly reduced. In Fxr-KO mice, the ability of Cga to mitigate liver damage induced by PAs was substantially reduced, which underscores the role of the SIRT1/FXR signaling axis in mediating the protective effects of Cga.

Conclusion: Our research suggests that Cga can serve as an effective treatment for PA-mediated hepatotoxicity. It appears that influencing the SIRT1/FXR signaling pathway might provide an innovative pharmacological approach to address liver damage caused by PAs.

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