Artesunate ameliorates high glucose-induced rat glomerular mesangial cell injury by suppressing the TLR4/NF-κB/NLRP3 inflammasome pathway.
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 μg/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 κB (NF-κB) p-p65, and nod-like receptor protein 3 (NLRP3). Inhibition of the TLR4/NF-κB 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-κB/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.
['Sun|Zhiqiang|Z|', 'Ma|Yali|Y|', 'Chen|Fang|F|', 'Wang|Shiying|S|', 'Chen|Baoping|B|', 'Shi|Jun|J|']
D000818:Animals D000962:Antimalarials D037621:Artemisinins D000077332:Artesunate D002460:Cell Line D049109:Cell Proliferation D005947:Glucose D058847:Inflammasomes D053583:Interleukin-1beta D015850:Interleukin-6 D008315:Malondialdehyde D050527:Mesangial Cells D053594:Myeloid Differentiation Factor 88 D016328:NF-kappa B D000071199:NLR Family, Pyrin Domain-Containing 3 Protein D051381:Rats D017382:Reactive Oxygen Species D015398:Signal Transduction D013482:Superoxide Dismutase D051197:Toll-Like Receptor 4 D014409:Tumor Necrosis Factor-alpha
Artesunate Diabetic nephropathy Oxidative stress Extracellular matrix accumulation Inflammation