PMID- 30031708 OWN - NLM STAT- MEDLINE DCOM- 20180918 LR - 20181202 IS - 1872-7786 (Electronic) IS - 0009-2797 (Linking) VI - 293 DP - 2018 Sep 25 TI - Artesunate ameliorates high glucose-induced rat glomerular mesangial cell injury by suppressing the TLR4/NF-kappaB/NLRP3 inflammasome pathway. PG - 11-19 LID - S0009-2797(18)30795-6 [pii] LID - 10.1016/j.cbi.2018.07.011 [doi] AB - Inflammatory response is important for the development and progression of diabetic nephropathy (DN). Artesunate (ART), an antimalarial drug, possesses anti-inflammatory effect and exhibits protective effect on chronic kidney diseases. However, the effect of ART on DN is unknown. The aim of the present study was to evaluate the effect and the molecular mechanism of ART on DN in an in vitro model. The rat mesangial cell line, HBZY-1, was induced by high glucose (HG; 30 mM d-glucose) in the presence or absence of ART (15 and 30 mug/ml) and incubated for 24 h. We found that HG induced the proliferation of HBZY-1 cells, while treatment with ART inhibited the cell proliferation. Treatment with ART inhibited HG-induced inflammatory cytokines production and expression of extracellular matrix (ECM). Besides, HG induced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and inhibited the superoxide dismutase (SOD) activity of HBZY-1 cells, and the effects were attenuated by ART treatment. ART decreased HG-induced the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), nuclear factor kappaB (NF-kappaB) p-p65, and nod-like receptor protein 3 (NLRP3). Inhibition of the TLR4/NF-kappaB pathway suppressed NLRP3 inflammasome in HBZY-1 cells. In conclusion, ART exhibited protective effect on HG-induced HBZY-1 cells by inhibiting the inflammatory response, oxidative stress and ECM accumulation. The TLR4/NF-kappaB/NLRP3 inflammasome pathway was involved in the protective effect of ART. The results suggested that ART might be a potential therapy agent for the DN treatment. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Sun, Zhiqiang AU - Sun Z AD - Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, PR China. FAU - Ma, Yali AU - Ma Y AD - Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, PR China. FAU - Chen, Fang AU - Chen F AD - Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, PR China. FAU - Wang, Shiying AU - Wang S AD - Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, PR China. FAU - Chen, Baoping AU - Chen B AD - Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, PR China. FAU - Shi, Jun AU - Shi J AD - Department of Nephrology, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, PR China. Electronic address: shijun_hh@163.com. LA - eng PT - Journal Article DEP - 20180719 PL - Ireland TA - Chem Biol Interact JT - Chemico-biological interactions JID - 0227276 RN - 0 (Antimalarials) RN - 0 (Artemisinins) RN - 0 (Inflammasomes) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Myd88 protein, rat) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Reactive Oxygen Species) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) RN - 4Y8F71G49Q (Malondialdehyde) RN - 60W3249T9M (Artesunate) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Antimalarials/*pharmacology MH - Artemisinins/*pharmacology MH - Artesunate MH - Cell Line MH - Cell Proliferation/drug effects MH - Glucose/toxicity MH - Inflammasomes/drug effects/*metabolism MH - Interleukin-1beta/analysis MH - Interleukin-6/analysis MH - Malondialdehyde/metabolism MH - Mesangial Cells/cytology/drug effects/metabolism MH - Myeloid Differentiation Factor 88/genetics/metabolism MH - NF-kappa B/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Rats MH - Reactive Oxygen Species/metabolism MH - Signal Transduction/*drug effects MH - Superoxide Dismutase/metabolism MH - Toll-Like Receptor 4/metabolism MH - Tumor Necrosis Factor-alpha/analysis OTO - NOTNLM OT - Artesunate OT - Diabetic nephropathy OT - Extracellular matrix accumulation OT - Inflammation OT - Oxidative stress EDAT- 2018/07/23 06:00 MHDA- 2018/09/19 06:00 CRDT- 2018/07/23 06:00 PHST- 2018/06/18 00:00 [received] PHST- 2018/07/11 00:00 [revised] PHST- 2018/07/16 00:00 [accepted] PHST- 2018/07/23 06:00 [pubmed] PHST- 2018/09/19 06:00 [medline] PHST- 2018/07/23 06:00 [entrez] AID - S0009-2797(18)30795-6 [pii] AID - 10.1016/j.cbi.2018.07.011 [doi] PST - ppublish SO - Chem Biol Interact. 2018 Sep 25;293:11-19. doi: 10.1016/j.cbi.2018.07.011. Epub 2018 Jul 19.