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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Frontiers Media S.A.
2025-01-01
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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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institution | Kabale University |
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language | English |
publishDate | 2025-01-01 |
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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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