Ganoderic acid alleviates chemotherapy-induced fatigue in mice bearing colon tumor  

作　　者：Abudumijiti Abulizi Ling Hu Ang Ma Fang-yu Shao Hui-ze Zhu Si-mei Lin Guang-ying Shao Yue Xu Jian-hua Ran Jing Li Hong Zhou Dong-mei Lin Lian-fu Wang Min Li Bao-xue Yang 

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs,Department of Pharmacology,School of Basic Medical Sciences,Peking University,Beijing 100191,China [2]Department of Anatomy and Laboratory of Neuroscience and Tissue Engineering,Basic Medical College,Chongqing Medical University,Chongqing 400016,China [3]Stem Cell and Tissue Engineering,Department of Histology and Embryology,Chongqing Medical University,Chongqing 400016,China [4]JUNCAO Technology Research Institute,Fujian Agriculture and Forestry University,Fuzhou 350002,China [5]Key Laboratory of Molecular Cardiovascular Sciences,Ministry of Education,Beijing 100191,China

出　　处：《Acta Pharmacologica Sinica》2021年第10期1703-1713,共11页中国药理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(grants 81620108029,81974083,81330074,81500535 and 81800388);the Beijing Natural Science Foundation(grant 7212151);the China Postdoctoral Science Foundation(grant 2018M630049).

摘　　要：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-αexpression 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.

关 键 词：ganoderic acid 5-FLUOROURACIL chemotherapy-related fatigue tumor-bearing mouse muscle HIPPOCAMPUS energy metabolism proinflammatory cytokine 

分 类 号：R735.35[医药卫生—肿瘤]