Ganoderic acid alleviates chemotherapy-induced fatigue in mice bearing colon tumor
Chemotherapy-related fatigue (CRF) is increasingly being recognized as one of the severe symptoms in patients undergoing chemotherapy, which not only largely reduces the quality of life in patients, but also diminishes their physical and social function. At present, there is no effective drug for pr...
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Veröffentlicht in: | Acta pharmacologica Sinica 2021-10, Vol.42 (10), p.1703-1713 |
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creator | Abulizi, Abudumijiti Hu, Ling Ma, Ang Shao, Fang-yu Zhu, Hui-ze Lin, Si-mei Shao, Guang-ying Xu, Yue Ran, Jian-hua Li, Jing Zhou, Hong Lin, Dong-mei Wang, Lian-fu Li, Min Yang, Bao-xue |
description | Chemotherapy-related fatigue (CRF) is increasingly being recognized as one of the severe symptoms in patients undergoing chemotherapy, which not only largely reduces the quality of life in patients, but also diminishes their physical and social function. At present, there is no effective drug for preventing and treating CRF. Ganoderic acid (GA), isolated from traditional Chinese medicine
Ganoderma lucidum
, has shown a variety of pharmacological activities such as anti-tumor, anti-inflammation, immunoregulation, etc. In this study, we investigated whether GA possessed anti-fatigue activity against CRF. CT26 tumor-bearing mice were treated with 5-fluorouracil (5-FU, 30 mg/kg) and GA (50 mg/kg) alone or in combination for 18 days. Peripheral and central fatigue-related behaviors, energy metabolism and inflammatory factors were assessed. We demonstrated that co-administration of GA ameliorated 5-FU-induced peripheral muscle fatigue-like behavior via improving muscle quality and mitochondria function, increasing glycogen content and ATP production, reducing lactic acid content and LDH activity, and inhibiting p-AMPK, IL-6 and TNF-α expression in skeletal muscle. Co-administration of GA also retarded the 5-FU-induced central fatigue-like behavior accompanied by down-regulating the expression of IL-6, iNOS and COX2 in the hippocampus through inhibiting TLR4/Myd88/NF-κB pathway. These results suggest that GA could attenuate 5-FU-induced peripheral and central fatigue in tumor-bearing mice, which provides evidence for GA as a potential drug for treatment of CRF in clinic. |
doi_str_mv | 10.1038/s41401-021-00669-6 |
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Ganoderma lucidum
, has shown a variety of pharmacological activities such as anti-tumor, anti-inflammation, immunoregulation, etc. In this study, we investigated whether GA possessed anti-fatigue activity against CRF. CT26 tumor-bearing mice were treated with 5-fluorouracil (5-FU, 30 mg/kg) and GA (50 mg/kg) alone or in combination for 18 days. Peripheral and central fatigue-related behaviors, energy metabolism and inflammatory factors were assessed. We demonstrated that co-administration of GA ameliorated 5-FU-induced peripheral muscle fatigue-like behavior via improving muscle quality and mitochondria function, increasing glycogen content and ATP production, reducing lactic acid content and LDH activity, and inhibiting p-AMPK, IL-6 and TNF-α expression in skeletal muscle. Co-administration of GA also retarded the 5-FU-induced central fatigue-like behavior accompanied by down-regulating the expression of IL-6, iNOS and COX2 in the hippocampus through inhibiting TLR4/Myd88/NF-κB pathway. These results suggest that GA could attenuate 5-FU-induced peripheral and central fatigue in tumor-bearing mice, which provides evidence for GA as a potential drug for treatment of CRF in clinic.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1038/s41401-021-00669-6</identifier><identifier>PMID: 33927358</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>5-Fluorouracil ; Animals ; Antineoplastic Agents - therapeutic use ; Biomedical and Life Sciences ; Biomedicine ; Cell Line, Tumor ; Chemotherapy ; Colonic Neoplasms - drug therapy ; Colonic Neoplasms - pathology ; Colorectal cancer ; Cyclooxygenase-2 ; Cytokines - metabolism ; Energy metabolism ; Energy Metabolism - drug effects ; Fatigue ; Female ; Fluorouracil - adverse effects ; Fluorouracil - therapeutic use ; Ganoderic acid ; Glycogen ; Hippocampus - drug effects ; Hippocampus - metabolism ; Immunology ; Immunoregulation ; Inflammation ; Interleukin 6 ; Internal Medicine ; Lactic acid ; Medical Microbiology ; Mice ; Mice, Inbred BALB C ; Mitochondria ; Muscle Fatigue - drug effects ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - pathology ; MyD88 protein ; NF-κB protein ; Nitric-oxide synthase ; Patients ; Pharmacology/Toxicology ; Quality of life ; Skeletal muscle ; TLR4 protein ; Toll-like receptors ; Traditional Chinese medicine ; Triterpenes - therapeutic use ; Tumor necrosis factor-α ; Vaccine</subject><ispartof>Acta pharmacologica Sinica, 2021-10, Vol.42 (10), p.1703-1713</ispartof><rights>The Author(s), under exclusive licence to CPS and SIMM 2021</rights><rights>2021. The Author(s), under exclusive licence to CPS and SIMM.</rights><rights>The Author(s), under exclusive licence to CPS and SIMM 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-635ad90ce0f4413063c3de6c2268a149e6c89aa41e2214a04819280ed4da2a623</citedby><cites>FETCH-LOGICAL-c474t-635ad90ce0f4413063c3de6c2268a149e6c89aa41e2214a04819280ed4da2a623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463583/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463583/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33927358$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abulizi, Abudumijiti</creatorcontrib><creatorcontrib>Hu, Ling</creatorcontrib><creatorcontrib>Ma, Ang</creatorcontrib><creatorcontrib>Shao, Fang-yu</creatorcontrib><creatorcontrib>Zhu, Hui-ze</creatorcontrib><creatorcontrib>Lin, Si-mei</creatorcontrib><creatorcontrib>Shao, Guang-ying</creatorcontrib><creatorcontrib>Xu, Yue</creatorcontrib><creatorcontrib>Ran, Jian-hua</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Zhou, Hong</creatorcontrib><creatorcontrib>Lin, Dong-mei</creatorcontrib><creatorcontrib>Wang, Lian-fu</creatorcontrib><creatorcontrib>Li, Min</creatorcontrib><creatorcontrib>Yang, Bao-xue</creatorcontrib><title>Ganoderic acid alleviates chemotherapy-induced fatigue in mice bearing colon tumor</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacol Sin</addtitle><addtitle>Acta Pharmacol Sin</addtitle><description>Chemotherapy-related fatigue (CRF) is increasingly being recognized as one of the severe symptoms in patients undergoing chemotherapy, which not only largely reduces the quality of life in patients, but also diminishes their physical and social function. At present, there is no effective drug for preventing and treating CRF. Ganoderic acid (GA), isolated from traditional Chinese medicine
Ganoderma lucidum
, has shown a variety of pharmacological activities such as anti-tumor, anti-inflammation, immunoregulation, etc. In this study, we investigated whether GA possessed anti-fatigue activity against CRF. CT26 tumor-bearing mice were treated with 5-fluorouracil (5-FU, 30 mg/kg) and GA (50 mg/kg) alone or in combination for 18 days. Peripheral and central fatigue-related behaviors, energy metabolism and inflammatory factors were assessed. We demonstrated that co-administration of GA ameliorated 5-FU-induced peripheral muscle fatigue-like behavior via improving muscle quality and mitochondria function, increasing glycogen content and ATP production, reducing lactic acid content and LDH activity, and inhibiting p-AMPK, IL-6 and TNF-α expression in skeletal muscle. Co-administration of GA also retarded the 5-FU-induced central fatigue-like behavior accompanied by down-regulating the expression of IL-6, iNOS and COX2 in the hippocampus through inhibiting TLR4/Myd88/NF-κB pathway. These results suggest that GA could attenuate 5-FU-induced peripheral and central fatigue in tumor-bearing mice, which provides evidence for GA as a potential drug for treatment of CRF in clinic.</description><subject>5-Fluorouracil</subject><subject>Animals</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colorectal cancer</subject><subject>Cyclooxygenase-2</subject><subject>Cytokines - metabolism</subject><subject>Energy metabolism</subject><subject>Energy Metabolism - drug effects</subject><subject>Fatigue</subject><subject>Female</subject><subject>Fluorouracil - adverse effects</subject><subject>Fluorouracil - therapeutic use</subject><subject>Ganoderic acid</subject><subject>Glycogen</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Immunology</subject><subject>Immunoregulation</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Internal Medicine</subject><subject>Lactic acid</subject><subject>Medical Microbiology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mitochondria</subject><subject>Muscle Fatigue - drug effects</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - pathology</subject><subject>MyD88 protein</subject><subject>NF-κB protein</subject><subject>Nitric-oxide synthase</subject><subject>Patients</subject><subject>Pharmacology/Toxicology</subject><subject>Quality of life</subject><subject>Skeletal muscle</subject><subject>TLR4 protein</subject><subject>Toll-like receptors</subject><subject>Traditional Chinese medicine</subject><subject>Triterpenes - therapeutic use</subject><subject>Tumor necrosis 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acid alleviates chemotherapy-induced fatigue in mice bearing colon tumor</title><author>Abulizi, Abudumijiti ; Hu, Ling ; Ma, Ang ; Shao, Fang-yu ; Zhu, Hui-ze ; Lin, Si-mei ; Shao, Guang-ying ; Xu, Yue ; Ran, Jian-hua ; Li, Jing ; Zhou, Hong ; Lin, Dong-mei ; Wang, Lian-fu ; Li, Min ; Yang, Bao-xue</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-635ad90ce0f4413063c3de6c2268a149e6c89aa41e2214a04819280ed4da2a623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>5-Fluorouracil</topic><topic>Animals</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Line, Tumor</topic><topic>Chemotherapy</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colorectal cancer</topic><topic>Cyclooxygenase-2</topic><topic>Cytokines - metabolism</topic><topic>Energy metabolism</topic><topic>Energy Metabolism - drug effects</topic><topic>Fatigue</topic><topic>Female</topic><topic>Fluorouracil - adverse effects</topic><topic>Fluorouracil - therapeutic use</topic><topic>Ganoderic acid</topic><topic>Glycogen</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Immunology</topic><topic>Immunoregulation</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Internal Medicine</topic><topic>Lactic acid</topic><topic>Medical Microbiology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mitochondria</topic><topic>Muscle Fatigue - drug effects</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - pathology</topic><topic>MyD88 protein</topic><topic>NF-κB protein</topic><topic>Nitric-oxide synthase</topic><topic>Patients</topic><topic>Pharmacology/Toxicology</topic><topic>Quality of life</topic><topic>Skeletal 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Guang-ying</au><au>Xu, Yue</au><au>Ran, Jian-hua</au><au>Li, Jing</au><au>Zhou, Hong</au><au>Lin, Dong-mei</au><au>Wang, Lian-fu</au><au>Li, Min</au><au>Yang, Bao-xue</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ganoderic acid alleviates chemotherapy-induced fatigue in mice bearing colon tumor</atitle><jtitle>Acta pharmacologica Sinica</jtitle><stitle>Acta Pharmacol Sin</stitle><addtitle>Acta Pharmacol Sin</addtitle><date>2021-10-01</date><risdate>2021</risdate><volume>42</volume><issue>10</issue><spage>1703</spage><epage>1713</epage><pages>1703-1713</pages><issn>1671-4083</issn><eissn>1745-7254</eissn><abstract>Chemotherapy-related fatigue (CRF) is increasingly being recognized as one of the severe symptoms in patients undergoing chemotherapy, which not only largely reduces the quality of life in patients, but also diminishes their physical and social function. At present, there is no effective drug for preventing and treating CRF. Ganoderic acid (GA), isolated from traditional Chinese medicine
Ganoderma lucidum
, has shown a variety of pharmacological activities such as anti-tumor, anti-inflammation, immunoregulation, etc. In this study, we investigated whether GA possessed anti-fatigue activity against CRF. CT26 tumor-bearing mice were treated with 5-fluorouracil (5-FU, 30 mg/kg) and GA (50 mg/kg) alone or in combination for 18 days. Peripheral and central fatigue-related behaviors, energy metabolism and inflammatory factors were assessed. We demonstrated that co-administration of GA ameliorated 5-FU-induced peripheral muscle fatigue-like behavior via improving muscle quality and mitochondria function, increasing glycogen content and ATP production, reducing lactic acid content and LDH activity, and inhibiting p-AMPK, IL-6 and TNF-α expression in skeletal muscle. Co-administration of GA also retarded the 5-FU-induced central fatigue-like behavior accompanied by down-regulating the expression of IL-6, iNOS and COX2 in the hippocampus through inhibiting TLR4/Myd88/NF-κB pathway. These results suggest that GA could attenuate 5-FU-induced peripheral and central fatigue in tumor-bearing mice, which provides evidence for GA as a potential drug for treatment of CRF in clinic.</abstract><cop>Singapore</cop><pub>Springer Singapore</pub><pmid>33927358</pmid><doi>10.1038/s41401-021-00669-6</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 5-Fluorouracil Animals Antineoplastic Agents - therapeutic use Biomedical and Life Sciences Biomedicine Cell Line, Tumor Chemotherapy Colonic Neoplasms - drug therapy Colonic Neoplasms - pathology Colorectal cancer Cyclooxygenase-2 Cytokines - metabolism Energy metabolism Energy Metabolism - drug effects Fatigue Female Fluorouracil - adverse effects Fluorouracil - therapeutic use Ganoderic acid Glycogen Hippocampus - drug effects Hippocampus - metabolism Immunology Immunoregulation Inflammation Interleukin 6 Internal Medicine Lactic acid Medical Microbiology Mice Mice, Inbred BALB C Mitochondria Muscle Fatigue - drug effects Muscle, Skeletal - drug effects Muscle, Skeletal - pathology MyD88 protein NF-κB protein Nitric-oxide synthase Patients Pharmacology/Toxicology Quality of life Skeletal muscle TLR4 protein Toll-like receptors Traditional Chinese medicine Triterpenes - therapeutic use Tumor necrosis factor-α Vaccine |
title | Ganoderic acid alleviates chemotherapy-induced fatigue in mice bearing colon tumor |
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