2. Academic Validation
  3. Cordycepin deteriorates 5' fluorouracil-induced anaemia by AMPK activation

Cordycepin deteriorates 5' fluorouracil-induced anaemia by AMPK activation

  • Eur J Pharmacol. 2025 Oct 11:1007:178232. doi: 10.1016/j.ejphar.2025.178232.
Lei Yang 1,  Siqi Kong 2,  Hailan Shi 2,  Liangyu Xu 2,  Zichen Wei 3,  Yafeng Chen 4,  Lei Fang 5
Affiliations

Affiliations

  • 1 Institute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, 225001, China; The Key Laboratory of the Jiangsu Higher Education Institutions for Nucleic Acid & Cell Fate Regulation (Yangzhou University), Yangzhou, 225001, China; Department of Pathology, The Second People's Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou, 213003, China.
  • 2 Institute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, 225001, China.
  • 3 Institute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, 225001, China; Department of Pathology, Dongtai Hospital of Chinese Medicine, Yancheng, 224200, China.
  • 4 Department of Hematology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China.
  • 5 Institute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, 225001, China; The Key Laboratory of the Jiangsu Higher Education Institutions for Nucleic Acid & Cell Fate Regulation (Yangzhou University), Yangzhou, 225001, China; Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530002, China. Electronic address: fanglei@yzu.edu.cn.
PMID: 41082995 DOI: 10.1016/j.ejphar.2025.178232
Abstract

Cordycepin (COR) is a compound extracted from Cordyceps sinensis. We found that COR exacerbates the acute anaemia induced by 5' fluorouracil (5-FU). Healthy mice were intraperitoneally injected with COR at doses of 2, 4, or 8 mg/kg for 10 consecutive days, which produced a slight decrease in the red cell distribution width in the peripheral blood and a reduction in the erythroblast levels in the spleen. Furthermore, COR (8 mg/kg) treatment delayed reticulocyte recovery when 5-FU was used to induce anaemia. A single 5-FU dose decreased the levels of reticulocytes and erythroblasts compared with those in the control mice; this decrease was more pronounced when COR was also administered. The percentage of reticulocytes was lower in the bone marrow of COR-treated mice than in the 5-FU group. COR treatment inhibited erythroid differentiation, characterised by a decrease in the proportion of erythroblasts and low mRNA levels of Hba, Hbb, Uros, Gata-1, and Epb42, compared with the control mice; these effects were reversed by treatment the AMPK Inhibitor, compound C. COR treatment also reduced the mitochondrial membrane potential. Mitochondrial matrix genes, such as those involved in haeme synthesis (Alas-2), metabolic Enzymes (Pck2 and Mthfd2), the respiratory chain (Ndufs7), and Autophagy (Atg4a and Atg4d) were downregulated in the COR-treated erythroid precursors. Compound C reversed the COR-induced decrease in the mitochondrial membrane potential as well as Alas-2, Pck2, Atg4a, and Atg4d mRNA levels. COR treatment substantially delayed reticulocyte recovery in the peripheral blood and reduced the number of erythroblasts in the spleen following 5-FU-induced anaemia. The mechanism of action of COR involves inhibiting erythroid differentiation via activating AMPK.

Keywords

5′ fluorouracil; AMPK; Anaemia; Cordycepin; Erythroid differentiation; Mitochondrion.

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