title: Isobavachalcone Attenuates MPTP-Induced Parkinson's Disease in Mice by Inhibition of Microglial Activation through NF-κB Pathway.
abstract: Parkinson's disease (PD) is a complex multi-system and age-related neurodegenerative disorder. The intervention targeting neuroinflammation in PD patients is one effective strategy to slow down or inhibit disease progression. Microglia-mediated inflammatory response plays an important role in Parkinson's, Alzheimer's and other cerebral diseases. Isobavachalcone is a main component of Chinese herb medicine Psoralea corylifolia, which function includes immunoregulation, anti-oxidation and the regulation of β-amyloid (Aβ42) deposited in hippocampus in Alzheimer's patients. Whether it has the therapeutic effect on Parkinson's disease, however, is unclear. In this study, we found that isobavachalcone could effectively remit Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), prolong the residence time of mice on Rota-rod and alleviate the neuronal necrosis. It also inhibited the over-activation of microglia, and decreased the expression of IL-6 and IL-1β in the brain of PD mice. In vitro, isobavachalcone could inhibit nuclear factor-kappaB (NF-κB) pathway through inhibiting the LPS-induced transfer of NF-κB subunit from cytoplasm to nucleus in BV-2 cells. Isobavachalcone decreased the LPS-induced oxidative stress and the expression of inflammatory cytokines, and provided a neuroprotective effect by antagonizing microglia-mediated inflammation. Our results indicated that isobavachalcone may be a candidated drug against Parkinson's disease with great clinical potential.
authors.affiliation: Laboratory of Genome Engineering, The Beijing Institute of Basic Medical Sciences, Beijing, China.|Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.
authors.forename: Haoran
authors.initials: H
authors.lastname: Jing
authors.affiliation: Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.
authors.forename: Shaoxia
authors.initials: S
authors.lastname: Wang
authors.affiliation: Laboratory of Genome Engineering, The Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Laboratory of Genome Engineering, The Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Fu
authors.affiliation: Laboratory of Genome Engineering, The Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Laboratory of Genome Engineering, The Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Donggang
authors.initials: D
authors.lastname: Xu
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D004195:Disease Models, Animal; D018836:Inflammation Mediators; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D017628:Microglia / Q000276:immunology* / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D047188:Chalcones; D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B; D018696:Neuroprotective Agents; C468754:isobavachalcone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D052247:Nitric Oxide Synthase Type II