title: Ginsenoside Rb1 improves postoperative fatigue syndrome by reducing skeletal muscle oxidative stress through activation of the PI3K/Akt/Nrf2 pathway in aged rats.
abstract: Ginsenoside Rb1 is reported to possess anti-fatigue activity, but the mechanisms remain unknown. The aim of this study was to investigate the molecular mechanisms responsible for the anti-fatigue effect of ginsenoside Rb1 on postoperative fatigue syndrome induced by major small intestinal resection (MSIR) in aged rat. Aged rats with MSIR were administrated with ginsenoside Rb1 (15 mg/kg) once a day from 3 days before surgery to the day of sacrifice, or with saline as corresponding controls. Rats without MSIR but going through the same surgery procedure were administrated with saline as blank controls. Anti-fatigue effect was assessed by an open field test; superoxide dismutase, reactive oxygen species and malondialdehyde in skeletal muscle were determined. The mRNA levels of Akt2 and Nrf2 in skeletal muscle were measured by real-time quantitative PCR. The activation of Akt and Nrf2 was examined by western blot and immunohistofluorescence. Our results revealed that ginsenoside Rb1 significantly increased the journey and the rearing frequency, decreased the time of rest in aged rats with MSIR. In addition, ginsenoside Rb1 significantly reduced reactive oxygen species and malondialdehyde release and increased the superoxide dismutase activity of skeletal muscle in aged rats with MSIR. Ginsenoside Rb1 also increased the expression of Akt2 and Nrf2 mRNA, up-regulated Akt phosphorylation and Nrf2 nuclear translocation. These findings indicate that ginsenoside Rb1 has an anti-fatigue effect on postoperative fatigue syndrome in aged rat, and the mechanism possibly involves activation of the PI3K/Akt pathway with subsequent Nrf2 nuclear translocation and induction of antioxidant enzymes.
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, 2 Fuxue Lane, Wenzhou 325000, Zhejiang Province, China.
authors: Cheng-Le
authors: CL
authors: Zhuang
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, 2 Fuxue Lane, Wenzhou 325000, Zhejiang Province, China.
authors: Xiang-Yu
authors: XY
authors: Mao
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, 2 Fuxue Lane, Wenzhou 325000, Zhejiang Province, China.
authors: Shu
authors: S
authors: Liu
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, 2 Fuxue Lane, Wenzhou 325000, Zhejiang Province, China.
authors: Wei-Zhe
authors: WZ
authors: Chen
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, 2 Fuxue Lane, Wenzhou 325000, Zhejiang Province, China.
authors: Dong-Dong
authors: DD
authors: Huang
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, 2 Fuxue Lane, Wenzhou 325000, Zhejiang Province, China.
authors: Chang-Jing
authors: CJ
authors: Zhang
authors: Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
authors: Bi-Cheng
authors: BC
authors: Chen
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, 2 Fuxue Lane, Wenzhou 325000, Zhejiang Province, China. Electronic address: shenxian5166@gmail.com.
authors: Xian
authors: X
authors: Shen
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, 2 Fuxue Lane, Wenzhou 325000, Zhejiang Province, China; Department of Surgery, Shanghai Tenth People׳s Hospital Affiliated to TongJi University, Shanghai 20072, China. Electronic address: yuzhen0577@gmail.com.
authors: Zhen
authors: Z
authors: Yu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005221:Fatigue / Q000188:drug therapy* / Q000378:metabolism*; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D008517:Phytotherapy; D011184:Postoperative Period; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013577:Syndrome
chemical_list: D036145:Ginsenosides; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; C442759:ginsenoside Rb1; D013482:Superoxide Dismutase; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: Ginsenoside Rb1; Ginsenoside Rb1 (PubChem CID: 71317070); Nrf2; Oxidative stress; PI3K/Akt; Postoperative fatigue syndrome