title: Astragaloside IV attenuates Toll-like receptor 4 expression via NF-κB pathway under high glucose condition in mesenchymal stem cells.
abstract: Diabetic hyperglycemia causes a variety of pathological changes. Astragaloside IV (AS-IV) was widely used for the treatment of cardiovascular diseases in China. The aim of this study was to determine the effect of AS-IV on bone marrow mesenchymal stem cells (MSCs) and the underlying mechanism in diabetes. We used reverse transcription polymerase chain reaction and western blotting to determine the expression of Toll-like receptor 4 (TLR4), matrix metalloproteinase-2 (MMP-2) and NF-κB p65 in MSCs under high glucose (HG) with or without pretreatment with AS-IV. The surface expression of TLR4 was checked by flow cytometry and the expression of TNF-α and MCP-1 were detected by ELISA in diabetes patients treated with AS-IV. AS-IV promoted the proliferation of MSCs and attenuated the increased expression of TLR4 induced by HG. In addition, AS-IV decreased the HG-induced translocation of NF-κB p65 and increased the MMP-2 expression in MSCs. AS-IV decreased the TLR4, TNF-α and MCP-1 expression in patients. Collectively,our data revealed that AS-IV attenuated TLR4 expression through the NF-κB signaling pathway in MSCs.
authors.affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular, and Metabolic Disorders, HuBei University of Science and Technology, Xianning 437100, PR China. mincaili01@gmail.com
authors.forename: Mincai
authors.initials: M
authors.lastname: Li
authors.forename: Liangzu
authors.initials: L
authors.lastname: Yu
authors.forename: Tonghui
authors.initials: T
authors.lastname: She
authors.forename: Yapin
authors.initials: Y
authors.lastname: Gan
authors.forename: Fuxin
authors.initials: F
authors.lastname: Liu
authors.forename: Zhengwu
authors.initials: Z
authors.lastname: Hu
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Chen
authors.forename: Suqin
authors.initials: S
authors.lastname: Li
authors.forename: Hongli
authors.initials: H
authors.lastname: Xia
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D012503:Saponins; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C052064:astragaloside A; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D005947:Glucose