Combination of Quercetin, Hirudin and Cinnamaldehyde Promotes Schwann Cell Differentiation and Myelination against High Glucose by Inhibiting ERK Signaling Pathway  

作　　者：LIU Di LIANG Xiao-chun SUN Ying WU Ya-nan ZHANG Hong 

机构地区：[1]Department of Traditional Chinese Medicine,Peking Union Medical College Hospital,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing 100730,China [2]Department of Cell Resource Center,Institute of Basic Medical Science,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing 100730,China [3]the Department of Nephrology,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China

出　　处：《Chinese Journal of Integrative Medicine》2020年第8期591-598,共8页中国结合医学杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China(No.81473639);the Youth Scientific Research Foundation of Peking Union Medical College(No.33320140118)。

摘　　要：Objective:To investigate the therapeutic and synergistic effects of QHC(combination of quercetin(Q),hirudin(H)and cinnamaldehyd(C))on Schwann cell differentiation and myelination against high glucose(HG)induced injury.Methods:Primary-culture Schwann cells exposed to HG(50 mmol/L)for 72 h and Schwann cell–dorsal root ganglion(DRG)neuron cocultures exposed to HG(50 mmol/L)for 7 days were employed as in vitro model of diabetic neuropathy.The cells were randomly divided into 10 groups:control(CON,25 mmol/L glucose),HG(50 mmol/L glucose),HG plus 10μmol/L quercetin(Q),HG plus 0.04 IU/mL hirudin(H),HG plus 100 nmol/L cinnamaldehyd(C),HG plus 10μmol/L quercetin and 0.04 IU/mL hirudin(QH),HG plus 10μmol/L quercetin and 50 nmol/L cinnamaldehyd(QC),HG plus 0.04 IU/mL hirudin and 50 nmol/L cinnamaldehyd(HC),HG plus 10μmol/L quercetin,0.04 IU/mL hirudin and 50 nmol/L cinnamaldehyd(QHC)or 10μmol/L U0126.Cell differentiation was evaluated by periaxin immunofluorescence staining.The protein expression levels of myelin protein zero(P0),myelin basic protein(MBP),myelin-associated glycoprotein(MAG),extracellular signal-regulated kinase(ERK),p-ERK,p-c-Jun,c-Jun,notch intracellular domain(NICD)and the mRNA expression levels of P0,MBP,MAG,Krox-20,Notch1 and Jagged1 were detected by Western blotting and real-time quantitative PCR analysis.The secretion of ciliary neurotrophic factor(CNTF)was determined by enzyme-linked immunosorbent assay(ELISA).The number and length of the myelin segments were evaluated by MBP immunofluorescence staining.The expression and the location of p-ERK in cocultures were detected by MAG and p-ERK immunofluorescence double staining.Results:Co-treatment with Q,C,H and their combination promoted Schwann cell differentiation,increased CNTF secretion,up-regulated the protein and m RNA expressions of myelin,and increased the number and length of the myelin segments(P<0.01 or P<0.05).In particular,the combination therapy of Q,H and C was superior to the respective monotherapy(P<0.01).Combination therapy of QH

关 键 词：diabetic peripheral neuropathy extracellular signal-regulated kinase pathway Schwann cells MYELINATION Chinese medicine synergistic effect 

分 类 号：R587.2[医药卫生—内分泌] R747.9[医药卫生—内科学]