title: Ganoderma lucidum polysaccharide accelerates refractory wound healing by inhibition of mitochondrial oxidative stress in type 1 diabetes.
abstract: OBJECTIVE
  Refractory wounds in diabetic patients constitute a serious complication that often leads to amputation with limited treatment regimens. The present study was designed to determine the protective effect of Ganoderma lucidum polysaccharide (Gl-PS) on diabetic wound healing and investigate underlying mechanisms.
  
  
  METHODS
  Streptozotocin (STZ)-induced type 1 diabetic mice with full-thickness excisional wounds were intragastrically administered with 10, 50 or 250 mg/kg/day of Gl-PS.
  
  
  RESULTS
  Gl-PS dose-dependently rescued the delay of wound closure in diabetic mice. 50 and 250 mg/kg/day of Gl-PS treatment significantly increased the mean perfusion rate around the wound in diabetic mice. Diabetic conditions markly increased mitochondrial superoxide anion (O(2)·(-)) production, nitrotyrosine formation, and inducible nitric oxide synthase (iNOS) activity in wound tissues, which were normalized with Gl-PS treatment. In diabetic wound tissues, the protein level of manganese superoxide dismutase (MnSOD) was unchanged whereas MnSOD activity was inhibited and its nitration was potentiated; Gl-PS administration suppressed MnSOD nitration and increased MnSOD and glutathione peroxidase (GPx) activities. Moreover, Gl-PS attenuated the redox enzyme p66Shc expression and phosphorylation dose-dependently in diabetic mice skin.
  
  
  CONCLUSIONS
  Gl-PS rescued the delayed wound healing and improved wound angiogenesis in STZ-induced type 1 diabetic mice, at least in part, by suppression of cutaneous MnSOD nitration, p66Shc and mitochondrial oxidative stress.
authors.affiliation: State Key Laboratory of Natural & Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, and Institute of System Biomedicine, Peking University, Beijing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Tie
authors.forename: Hong-Qin
authors.initials: HQ
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: An
authors.forename: Shao-Qiang
authors.initials: SQ
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Li
authors.forename: Alex F
authors.initials: AF
authors.lastname: Chen
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Lin
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Li
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D011134:Polysaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D020940:Reishi / Q000737:chemistry*; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013311:Streptozocin / Q000008:administration & dosage / Q000009:adverse effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014945:Wound Healing
chemical_list: D007004:Hypoglycemic Agents; D011134:Polysaccharides; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C002744:3-nitrotyrosine; D014443:Tyrosine; D013311:Streptozocin; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D013482:Superoxide Dismutase