title: Sesquiterpene lactones and their derivatives inhibit high glucose-induced NF-κB activation and MCP-1 and TGF-β1 expression in rat mesangial cells.
abstract: Diabetic nephropathy (DN) is one of the most common and serious chronic complications of diabetes mellitus, however, no efficient clinical drugs exist for the treatment of DN. We selected and synthesized several sesquiterpene lactones (SLs), and then used the MTT assay to detect rat mesangial cells (MCs) proliferation, ELISA to measure the expression level of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-β1) and fibronectin(FN), real-time fluorescent quantitative PCR analysis to measure the MCP-1 and TGF-β1 gene expression, western blot to detect the level of IκBα protein and EMSA to measure the activation of nuclear factor kappa B (NF-κB). We discovered that SLs, including parthenolide (PTL), micheliolide (MCL), arglabin, and isoalantolactone (IAL), as well as several synthetic analogs of these molecules, could effectively attenuate the high glucose-stimulated activation of NF-κB, the degradation of IκBα, and the expression of MCP-1, TGF-β1 and FN in rat mesangial cells (MCs). These findings suggest that SLs and their derivatives have potential as candidate drugs for the treatment of DN.
authors.affiliation: Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, China. zjyy@smu.edu.cn.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Jia
authors.forename: Jian-Cheng
authors.initials: JC
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Long
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Si-Jia
authors.initials: SJ
authors.lastname: Chen
authors.forename: Jia-Dai
authors.initials: JD
authors.lastname: Zhai
authors.forename: Lian-Bo
authors.initials: LB
authors.lastname: Wei
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Long
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000502:physiology*; D007783:Lactones / Q000138:chemical synthesis / Q000494:pharmacology*; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D007783:Lactones; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D005947:Glucose