Artesunate activates Nrf2 pathway-driven anti-inflammatory potential through ERK signaling in microglial BV2 cells.
Chronic inflammatory response in the brain is a characteristic etiopathology of various neurodegenerative diseases; consequently increasing the intrinsic anti-inflammatory potency could be an especially desirable strategy to prevent inflammation-related neuronal injuries. Transcription factor NF-E2-related factor-2 (Nrf2)-mediated control of redox homeostasis may participate in the modulation of microglial responses by regulating expression of important antioxidant and phase II detoxification genes. In our present work, we show that artesunate, a semi-synthetic derivative of anti-malarial agent artemisinin, attenuates LPS-induced inflammatory responses in microglial BV2 cells. Artesunate activates Nrf2-ARE system, and leads to an increase in the level of downstream heme oxygenase-1. Artesunate also activates PI3K/Akt, ERK, and JNK MAPKs signaling, but artesunate-induced activation of Nrf2 signaling and up-regulation of heme oxygenase-1 are ERK pathway-dependent. Collectively, this study demonstrates that artesunate is a potential activator of the Nrf2/ARE-dependent pathway and is therapeutically relevant to inflammatory responses of microglial cells.
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, South Korea.
Ik-Soo
IS
Lee
Dae-Kwang
DK
Ryu
Juhee
J
Lim
Sera
S
Cho
Bok Yun
BY
Kang
Hyun Jin
HJ
Choi
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control
D000962:Antimalarials; D037621:Artemisinins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D000077332:Artesunate; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases