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

ObjectiveTo 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.MethodsBALB/c mice inoculated with C26 colon cancer cells were treated with paclitaxel (PTX, 10 mg/kg) and...

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Main Authors: Shilei Zhang, Fukai Gong, Jiali Liu, Shuping You, Tao Liu, Jianhua Yang, Junping Hu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2024.1370264/full
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author Shilei Zhang
Fukai Gong
Jiali Liu
Shuping You
Tao Liu
Jianhua Yang
Junping Hu
author_facet Shilei Zhang
Fukai Gong
Jiali Liu
Shuping You
Tao Liu
Jianhua Yang
Junping Hu
author_sort Shilei Zhang
collection DOAJ
description ObjectiveTo 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.MethodsBALB/c mice inoculated with C26 colon cancer cells were treated with paclitaxel (PTX, 10 mg/kg) and ACT (100 mg/kg) alone or in combination for 21 days. Fatigue-associated 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 proteins and ACT was verified by Surface plasmon resonance (SPR) assay.ResultsOur 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.ConclusionThis study suggests that ACT derived from C. tubulosa harbors protective properties against cancer-related fatigue mediated by tumor cells.
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spelling doaj-art-5e5b185b6e63435c90a619112aa7e4a32025-01-13T05:10:47ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.13702641370264Effects of acteoside from Cistanche tubulosa on the plasma metabolome of cancer-related fatigue mice inoculated with colon cancer cellsShilei Zhang0Fukai Gong1Jiali Liu2Shuping You3Tao Liu4Jianhua Yang5Junping Hu6State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Central Laboratory, School of Public Health, Xinjiang Medical University, Urumqi, ChinaDepartment of Pharmacy, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Pharmacognosy, School of Pharmacy, Xinjiang Medical University, Urumqi, ChinaDepartment of Basic Nursing, School of Nursing, Xinjiang Medical University, Urumqi, ChinaDepartment of Toxicology, School of Public Health, Xinjiang Medical University, Urumqi, ChinaDepartment of Pharmacy, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Pharmacognosy, School of Pharmacy, Xinjiang Medical University, Urumqi, ChinaObjectiveTo 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.MethodsBALB/c mice inoculated with C26 colon cancer cells were treated with paclitaxel (PTX, 10 mg/kg) and ACT (100 mg/kg) alone or in combination for 21 days. Fatigue-associated 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 proteins and ACT was verified by Surface plasmon resonance (SPR) assay.ResultsOur 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.ConclusionThis study suggests that ACT derived from C. tubulosa harbors protective properties against cancer-related fatigue mediated by tumor cells.https://www.frontiersin.org/articles/10.3389/fphar.2024.1370264/fullside effects of radiotherapy and chemotherapycancer-related fatiguemetabolomicsCistanche tubulosaacteoside
spellingShingle Shilei Zhang
Fukai Gong
Jiali Liu
Shuping You
Tao Liu
Jianhua Yang
Junping Hu
Effects of acteoside from Cistanche tubulosa on the plasma metabolome of cancer-related fatigue mice inoculated with colon cancer cells
Frontiers in Pharmacology
side effects of radiotherapy and chemotherapy
cancer-related fatigue
metabolomics
Cistanche tubulosa
acteoside
title Effects of acteoside from Cistanche tubulosa on the plasma metabolome of cancer-related fatigue mice inoculated with colon cancer cells
title_full Effects of acteoside from Cistanche tubulosa on the plasma metabolome of cancer-related fatigue mice inoculated with colon cancer cells
title_fullStr Effects of acteoside from Cistanche tubulosa on the plasma metabolome of cancer-related fatigue mice inoculated with colon cancer cells
title_full_unstemmed Effects of acteoside from Cistanche tubulosa on the plasma metabolome of cancer-related fatigue mice inoculated with colon cancer cells
title_short Effects of acteoside from Cistanche tubulosa on the plasma metabolome of cancer-related fatigue mice inoculated with colon cancer cells
title_sort effects of acteoside from cistanche tubulosa on the plasma metabolome of cancer related fatigue mice inoculated with colon cancer cells
topic side effects of radiotherapy and chemotherapy
cancer-related fatigue
metabolomics
Cistanche tubulosa
acteoside
url https://www.frontiersin.org/articles/10.3389/fphar.2024.1370264/full
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