title: Paeoniflorin protects Schwann cells against high glucose induced oxidative injury by activating Nrf2/ARE pathway and inhibiting apoptosis.
abstract: BACKGROUND
  Paeoniflorin (PF) is the principal bioactive component of Paeonia lactiflora Pall., which an included in Tang Luo Ning recipe, a traditional Chinese herbal medicine based on Huangqi Guizhi Wuwu decoction. PF is also widely used in Traditional Chinese Medicine for the treatment of blood-arthralgia disease including diabetic peripheral neuropathy (DPN), but its underlying molecular mechanism of neuroprotective effects is not yet well understood. Diabetic hyperglycemia induced oxidative stress in Schwann cells, an important component of the peripheral nervous system, has been proposed as a unifying mechanism for DPN. The objective of this study is to determine the effects of PF on Schwann cells oxidative stress and apoptosis induced by high glucose.
  
  
  METHODS
  RSC96 cells, a Schwann cell line, were treated with high glucose (150mM) and PF (1, 10 and 100μM). Subsequently, MTT assay was performed. The level of apoptosis was examined by flow cytometry and the oxidative stress was reflected by reactive oxygen species (ROS), malondialdehyde (MDA), glutathione S-transferases (GST) and glutathione peroxidase (GPX) levels. The mRNA expressions of Nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were detected by qRT-PCR. The levels of Kelch-like ECH-associating protein 1 (Keap1), Nrf2, HO-1, γ-glutamylcysteine synthetase (γGCS), B-cell CLL/lymphoma 2 (Bcl-2), Bax and Caspase 3 were detected by High content analysis and/or Western blot.
  
  
  RESULTS
  The role of PF markedly suppressed high glucose induced Schwann cells oxidative stress by decreasing ROS and MDA levels and increasing GST and GPX activity. Western blot analysis showed that PF induced nuclear translocation of Nrf2. High content analysis showed that PF promoted Nrf2 dissociation from Keap1 and upregulating the Nrf2/ antioxidant response element (ARE) pathway. Furthermore, PF reduced Schwann cells apoptosis by increasing Bcl-2 and inhibiting Bax and Caspase-3 expressions.
  
  
  CONCLUSIONS
  PF in the management of Schwann cells oxidative stress induced by high glucose may be associated with activation of Nrf2/ARE pathway and Bcl-2-related apoptotic pathway.
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, #10, Youanmenwai Xitoutiao, Fengtai District, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, #10, Youanmenwai Xitoutiao, Fengtai District, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Yao
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, #10, Youanmenwai Xitoutiao, Fengtai District, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research China.
authors.forename: Haotian
authors.initials: H
authors.lastname: Shi
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, #10, Youanmenwai Xitoutiao, Fengtai District, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research China.
authors.forename: Haolong
authors.initials: H
authors.lastname: Liu
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, #10, Youanmenwai Xitoutiao, Fengtai District, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research China.
authors.forename: Yangfan
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, #10, Youanmenwai Xitoutiao, Fengtai District, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, #10, Youanmenwai Xitoutiao, Fengtai District, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research China.
authors.forename: Renhui
authors.initials: R
authors.lastname: Liu
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, #10, Youanmenwai Xitoutiao, Fengtai District, Beijing 100069, China. Electronic address: xulp@ccmu.edu.cn.
authors.forename: Liping
authors.initials: L
authors.lastname: Xu
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage / Q000633:toxicity*; D005960:Glucosides / Q000494:pharmacology*; D039821:Monoterpenes / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012583:Schwann Cells / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D006027:Glycosides
chemical_list: D053148:Caspase 3; D005947:Glucose; D005960:Glucosides; D039821:Monoterpenes; D051267:NF-E2-Related Factor 2; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C494828:Bax protein, rat; C495637:Nfe2l2 protein, rat; C015423:peoniflorin; D006027:Glycosides
keywords: Apoptosis; BCl-2; Nrf2; Oxidative stress; Peoniflorin; Schwann cells