PMID- 24152676 OWN - NLM STAT- MEDLINE DCOM- 20140422 LR - 20211021 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 18 IP - 10 DP - 2013 Oct 21 TI - Sesquiterpene lactones and their derivatives inhibit high glucose-induced NF-kappaB activation and MCP-1 and TGF-beta1 expression in rat mesangial cells. PG - 13061-77 LID - 10.3390/molecules181013061 [doi] AB - 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-beta1) and fibronectin(FN), real-time fluorescent quantitative PCR analysis to measure the MCP-1 and TGF-beta1 gene expression, western blot to detect the level of IkappaBalpha protein and EMSA to measure the activation of nuclear factor kappa B (NF-kappaB). 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-kappaB, the degradation of IkappaBalpha, and the expression of MCP-1, TGF-beta1 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. FAU - Jia, Qian-Qian AU - Jia QQ AD - Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, China. zjyy@smu.edu.cn. FAU - Wang, Jian-Cheng AU - Wang JC FAU - Long, Jing AU - Long J FAU - Zhao, Yan AU - Zhao Y FAU - Chen, Si-Jia AU - Chen SJ FAU - Zhai, Jia-Dai AU - Zhai JD FAU - Wei, Lian-Bo AU - Wei LB FAU - Zhang, Quan AU - Zhang Q FAU - Chen, Yue AU - Chen Y FAU - Long, Hai-Bo AU - Long HB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131021 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Lactones) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Reactive Oxygen Species) RN - 0 (Sesquiterpenes) RN - 0 (Tgfb1 protein, rat) RN - 0 (Transforming Growth Factor beta1) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Chemokine CCL2/genetics/*metabolism MH - Diabetic Nephropathies/drug therapy MH - Drug Evaluation, Preclinical MH - Gene Expression/drug effects MH - Gene Expression Regulation/drug effects MH - Glucose/*physiology MH - Lactones/chemical synthesis/*pharmacology MH - Mesangial Cells/drug effects/*metabolism MH - NF-kappa B/*metabolism MH - Protein Binding MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Reactive Oxygen Species/metabolism MH - Sesquiterpenes/chemical synthesis/*pharmacology MH - Transforming Growth Factor beta1/genetics/*metabolism PMC - PMC6269856 EDAT- 2013/10/25 06:00 MHDA- 2014/04/23 06:00 PMCR- 2013/10/21 CRDT- 2013/10/25 06:00 PHST- 2013/09/12 00:00 [received] PHST- 2013/09/12 00:00 [revised] PHST- 2013/10/14 00:00 [accepted] PHST- 2013/10/25 06:00 [entrez] PHST- 2013/10/25 06:00 [pubmed] PHST- 2014/04/23 06:00 [medline] PHST- 2013/10/21 00:00 [pmc-release] AID - molecules181013061 [pii] AID - molecules-18-13061 [pii] AID - 10.3390/molecules181013061 [doi] PST - epublish SO - Molecules. 2013 Oct 21;18(10):13061-77. doi: 10.3390/molecules181013061.