Shizukaol B, an active sesquiterpene from Chloranthus henryi, attenuates LPS-induced inflammatory responses in BV2 microglial cells.
The objective of the current study was to evaluate the anti-inflammatory effects of shizukaol B, a lindenane-type dimeric sesquiterpene isolated from the whole plant of Chloranthus henryi, on lipopolysaccharide (LPS)-induced activation of BV2 microglial cells in vitro. Our data showed that shizukaol B concentration-dependently suppressed expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in LPS-stimulated BV2 microglia. Meanwhile, shizukaol B concentration- and time-dependently inhibited LPS-mediated c-Jun N-terminal kinase 1/2 (JNK) activation, but had little effect on extracellular signal-regulated kinase 1/2 or p38 phosphorylation. Furthermore, shizukaol B significantly blocked LPS-induced activator protein-1 (AP-1) activation, evidenced by reduced phosphorylation and nuclear translocation of c-Jun and DNA binding activity of AP-1. Taken together, our findings suggest that shizukaol B exerts anti-inflammatory effects in LPS-activated microglia partly by modulating JNK-AP-1 signaling pathway.
Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
Li-Long
LL
Pan
Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
Peng
P
Xu
Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
Xiao-Ling
XL
Luo
Department of Natural Products Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China.
Li-Jun
LJ
Wang
Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
Si-Yu
SY
Liu
Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
Yi-Zhun
YZ
Zhu
Department of Natural Products Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: jfhu@fudan.edu.cn.
Jin-Feng
JF
Hu
Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: liuxinhua@fudan.edu.cn.
Xin-Hua
XH
Liu
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors; D064028:Tracheophyta / Q000737:chemistry*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012717:Sesquiterpenes; D018808:Transcription Factor AP-1; C000615622:shizukaol B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
Activator protein-1; BV2 microglia cells; Lipopolysaccharide; Neuro-inflammation; Shizukaol B