title: Curcumin exerts anti-inflammatory and antioxidative properties in 1-methyl-4-phenylpyridinium ion (MPP(+))-stimulated mesencephalic astrocytes by interference with TLR4 and downstream signaling pathway.
abstract: Neuroinflammation is closely associated with the pathophysiology of neurodegenerative diseases including Parkinson's disease (PD). Recent evidence indicates that astrocytes also play pro-inflammatory roles in the central nervous system (CNS) by activation with toll-like receptor (TLR) ligands. Therefore, targeting anti-inflammation may provide a promising therapeutic strategy for PD. Curcumin, a polyphenolic compound isolated from Curcuma longa root, has been commonly used for the treatment of neurodegenerative diseases. However, the details of how curcumin exerts neuroprotection remain uncertain. Here, we investigated the protective effect of curcumin on 1-methyl-4-phenylpyridinium ion-(MPP(+)-) stimulated primary astrocytes. Our results showed that MPP(+) stimulation resulted in significant production of tumor necrosis factor (TNF)-α, interleukin (IL-6), and reactive oxygen species (ROS) in primary mesencephalic astrocytes. Curcumin pretreatment decreased the levels of these pro-inflammatory cytokines while increased IL-10 expression in MPP(+)-stimulated astrocytes. In addition, curcumin increased the levels of antioxidant glutathione (GSH) and reduced ROS production. Our results further showed that curcumin decreased the levels of TLR4 and its downstream effectors including NF-κB, IRF3, MyD88, and TIRF that are induced by MPP(+) as well as inhibited the immunoreactivity of TLR4 and morphological activation in MPP(+)-stimulated astrocytes. Together, data suggest that curcumin might exert a beneficial effect on neuroinflammation in the pathophysiology of PD.
authors.affiliation: Department of Histology and Embryology, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Histology and Embryology, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Sports Medicine, Shenyang Sports University, Shenyang, Liaoning, 110102, People's Republic of China.
authors.forename: Xingliang
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Histology and Embryology, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiac Function, The Second Staff Hospital of Liaohe Oilfield Company, Panjin, Liaoning, 124011, People's Republic of China.
authors.forename: Sujie
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Mental Diseases, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Internal Medicine of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, 79 East Chongshan Road, Shenyang, Liaoning, 110847, People's Republic of China. shiyan012@sina.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
mesh_terms: D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D018836:Inflammation Mediators / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D008636:Mesencephalon / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D050838:Interferon Regulatory Factor-3; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D003474:Curcumin; D015655:1-Methyl-4-phenylpyridinium
keywords: 1-Methyl-4-phenylpyridinium ion; Astrocytes; Curcumin; Neuroinflammation; Oxidative stress; Toll-like receptor 4