title: A tetramethoxychalcone from Chloranthus henryi suppresses lipopolysaccharide-induced inflammatory responses in BV2 microglia.
abstract: Neuroinflammation underlies the pathogenesis and progression of neurodegenerative diseases. 2׳-hydroxy-4,3׳,4׳,6׳-tetramethoxychalcone (HTMC) is a known chalcone derivative isolated from Chloranthus henryi with anti-inflammatory activities in BV2 macrophages. However, its pharmacological effects on microglial cells have not been demonstrated. To this end, we examined the effects of HTMC on lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglial cells. HTMC concentration-dependently inhibited LPS-induced expression of inflammatory enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nitric oxide (NO) production, and the secretion of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. In addition, HTMC inhibited reactive oxygen species (ROS) production by reducing NADPH oxidase (Nox) 2 and Nox4 expression. In addition, HTMC interfered LPS-induced c-Jun N-terminal kinase 1/2 (JNK) phosphorylation in a time- and concentration-dependent manner. By inhibiting phosphorylation and nuclear translocation of Jun, HTMC suppressed LPS-induced activator protein-1 (AP-1) activation. Taken together, our data indicate that HTMC suppresses inflammatory responses in LPS-stimulated BV2 microglial cells by modulating JNK-AP-1 and NADPH oxidases-ROS pathways. HTMC represents a promising therapeutic agent for neurodegenerative and related aging-associated diseases.
authors: Shanghai Key Laboratory of Bioactive Small Molecules and Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors: Xiao-Ling
authors: XL
authors: Luo
authors: Shanghai Key Laboratory of Bioactive Small Molecules and Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors: Si-Yu
authors: SY
authors: Liu
authors: Department of Natural Products Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors: Li-Jun
authors: LJ
authors: Wang
authors: Shanghai Key Laboratory of Bioactive Small Molecules and Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors: Qiu-Yan
authors: QY
authors: Zhang
authors: Shanghai Key Laboratory of Bioactive Small Molecules and Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors: Peng
authors: P
authors: Xu
authors: Shanghai Key Laboratory of Bioactive Small Molecules and Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: panlilong@fudan.edu.cn.
authors: Li-Long
authors: LL
authors: Pan
authors: Department of Natural Products Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: jfhu@fudan.edu.cn.
authors: Jin-Feng
authors: JF
authors: Hu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D047188:Chalcones / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D064028:Tracheophyta / Q000737:chemistry*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D047188:Chalcones; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D019255:NADPH Oxidases; D048031:JNK Mitogen-Activated Protein Kinases
keywords: 2׳-Hydroxy-4,3׳,4׳,6׳-tetramethoxychalcone; Anti-neuroinflammatory activities; Ap-1; Inflammatory mediators; Signaling pathways