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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Drug Metabolism and Transport
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1370264
This article is part of the Research Topic Drug Metabolism and Transport: The Frontier of Personalized Medicine Volume II View all 17 articles

Effects of acteoside from Cistanche tubulosa on the plasma metabolome of Cancer-related fatigue mice inoculated with colon cancer cells

Provisionally accepted
Shilei Zhang Shilei Zhang 1Fukai Gong Fukai Gong 2*Jiali Liu Jiali Liu 3Shuping You Shuping You 4*Tao Liu Tao Liu 1Jianhua Yang Jianhua Yang 5,6*Junping Hu Junping Hu 3*
  • 1 School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang Uyghur Region, China
  • 2 Department of Pharmacy, People′s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uyghur Region, China
  • 3 School of Pharmacy, Xinjiang Medical University, Urumqi, China
  • 4 School of Nursing, Xinjiang Medical University, Urumqi, China
  • 5 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, China
  • 6 Department of Pharmacy, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

The final, formatted version of the article will be published soon.

    To elucidate the metabolic mechanisms by which acteoside (ACT) isolated from Cistanche tubulosa alleviates cancer-related fatigue (CRF) in a murine model of colon cancer with cachexia.Methods: BALB/c mice inoculated with C26 colon cancer cells were treated with paclitaxel (PTX, 10 mg/kg) and ACT (50, 100 mg/kg) alone or in combination for 21 days. Fatigueassociated behaviors, tumor inhibition rate, and skeletal muscle morphology assessed by hematoxylin-eosin (H&E) staining and electron microscopy were evaluated. Finally, liquid chromatography-mass spectrometry (LC/MS) was employed to investigate alterations in the plasma metabolic profile of tumor-bearing mice with CRF in response to ACT treatment, and the affinity between metabolite-associated genesproteins and ACT was verified by Surface plasmon resonance (SPR) assay.Our study demonstrated the presence of CRF in the colon cancer mouse model, with the severity of fatigue increasing alongside tumor growth. Administration of ACT ameliorated both tumor burden and PTX-induced muscle fatigue-like behavior. LC/MS analysis identified a panel of differentially regulated metabolites, including trans-aconitine, citric acid, 3-coumaric acid, ephedrine, thymine, cytosine, indole-3-acetic acid, and pantothenol-9. These metabolites were primarily enriched in pathways associated with valine biosynthesis, tyrosine metabolism, tryptophan metabolism, and biosynthesis of pyridine alkaloids. Furthermore, several key enzymes, including CYP3A4, CYP19A1, CYP2E1, TNF, BCL-2, RYR2, and ATP2A1, were identified as potential targets underlying the anti-CRF effects of ACT.This study suggests that ACT derived from Cistanche tubulosa harbors protective properties against cancer-related fatigue mediated by tumor cells.

    Keywords: Side effects of radiotherapy and chemotherapy, Cancer-related fatigue, Metabolomics, Cistanche tubulosa, Acteoside

    Received: 14 Jan 2024; Accepted: 17 Dec 2024.

    Copyright: © 2024 Zhang, Gong, Liu, You, Liu, Yang and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Fukai Gong, Department of Pharmacy, People′s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, Xinjiang Uyghur Region, China
    Shuping You, School of Nursing, Xinjiang Medical University, Urumqi, 830011, China
    Jianhua Yang, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, China
    Junping Hu, School of Pharmacy, Xinjiang Medical University, Urumqi, China

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