title: Arctigenin enhances swimming endurance of sedentary rats partially by regulation of antioxidant pathways.
abstract: OBJECTIVE
  Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan found in traditional Chinese herbs, has been determined to exhibit a variety of pharmacological activities, including anti-tumor, anti-inflammation, neuroprotection, and endurance enhancement. In the present study, we investigated the antioxidation and anti-fatigue effects of arctigenin in rats.
  
  
  METHODS
  Rat L6 skeletal muscle cell line was exposed to H2O2 (700 μmol/L), and ROS level was assayed using DCFH-DA as a probe. Male SD rats were injected with arctigenin (15 mg·kg(-1)·d(-1), ip) for 6 weeks, and then the weight-loaded forced swimming test (WFST) was performed to evaluate their endurance. The levels of antioxidant-related genes in L6 cells and the skeletal muscles of rats were analyzed using real-time RT-PCR and Western blotting.
  
  
  RESULTS
  Incubation of L6 cells with arctigenin (1, 5, 20 μmol/L) dose-dependently decreased the H2O2-induced ROS production. WFST results demonstrated that chronic administration of arctigenin significantly enhanced the endurance of rats. Furthermore, molecular biology studies on L6 cells and skeletal muscles of the rats showed that arctigenin effectively increased the expression of the antioxidant-related genes, including superoxide dismutase (SOD), glutathione reductase (Gsr), glutathione peroxidase (GPX1), thioredoxin (Txn) and uncoupling protein 2 (UCP2), through regulation of two potential antioxidant pathways: AMPK/PGC-1α/PPARα in mitochondria and AMPK/p53/Nrf2 in the cell nucleus.
  
  
  CONCLUSIONS
  Arctigenin efficiently enhances rat swimming endurance by elevation of the antioxidant capacity of the skeletal muscles, which has thereby highlighted the potential of this natural product as an antioxidant in the treatment of fatigue and related diseases.
authors.affiliation: School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Ruo-ming
authors.initials: RM
authors.lastname: Wu
authors.affiliation: School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Sun
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Zhi-yuan
authors.initials: ZY
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Zhuang
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Tang
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Hu
authors.affiliation: 1] School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China [2] Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Shen
mesh_terms: D000818:Animals; D008297:Male; D051381:Rats; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D005221:Fatigue / Q000188:drug therapy / Q000378:metabolism; D005663:Furans / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000502:physiology; D010807:Physical Endurance / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013550:Swimming / Q000502:physiology; D013879:Thioredoxins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000071246:Uncoupling Protein 2; D051267:NF-E2-Related Factor 2 / Q000378:metabolism
chemical_list: D055372:AMP-Activated Protein Kinases; D000975:Antioxidants; C071942:arctigenin; D005663:Furans; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D006861:Hydrogen Peroxide; D007473:Ion Channels; D017705:Lignans; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047495:PPAR gamma; C501429:Ppargc1a protein, rat; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D013879:Thioredoxins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat