title: α-Asarone attenuates microglia-mediated neuroinflammation by inhibiting NF kappa B activation and mitigates MPTP-induced behavioral deficits in a mouse model of Parkinson's disease.
abstract: The selective loss of dopaminergic neurons in Parkinson's disease (PD) is associated with microglial activation. Therefore, the importance of early therapeutic intervention to inhibit microglial activation would be an effective strategy to alleviate the progression of PD. α-Asarone, an active compound found in Araceae and Annonaceae plant species has been used to improve various disease conditions including central nervous system disorders. In the present study the in vitro and in vivo therapeutic effects of α-asarone isolated from the rhizome of Acorus gramineus Solander was evaluated on microglia-mediated neuroinflammation and neuroprotection. Lipopolysaccharide (LPS)-stimulated BV-2 microglial cells were used to evaluate in vitro effects. 1-methyl-4 phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced mouse model of PD was developed to study the neuroprotective effects of α-asarone in vivo. The results indicated that α-asarone significantly attenuated the LPS-stimulated increase in neuroinflammatory responses and suppressed pro-inflammatory cytokine production in BV-2 cells. Mechanistic study revealed that α-asarone inhibited the LPS-stimulated activation via regulation of nuclear factor kappa-B by blocking degradation of inhibitor kappa B-alpha signaling in BV-2 microglial cells. In in vivo studies, MPTP intoxication to mice resulted in brain microglial activation and significant behavioral deficits. Prophylactic treatment with α-asarone suppressed microglial activation and attenuated PD-like behavioral impairments as assessed by the Y-maze and pole tests. Taken together, these data demonstrate that α-asarone is a promising neuroprotective agent that should be further evaluated and developed for future prevention and treatment of microglia-mediated neuroinflammatory conditions including PD.
authors.affiliation: Department of Biotechnology, Konkuk University, 380-701, South Korea.
authors.forename: Byung-Wook
authors.initials: BW
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Konkuk University, 380-701, South Korea.
authors.forename: Sushruta
authors.initials: S
authors.lastname: Koppula
authors.affiliation: Department of Biotechnology, Konkuk University, 380-701, South Korea.
authors.forename: Hemant
authors.initials: H
authors.lastname: Kumar
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, South Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Biomedical Chemistry, Konkuk University, 380-701, South Korea.
authors.forename: Il-Woung
authors.initials: IW
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Konkuk University, 380-701, South Korea.
authors.forename: Sandeep V
authors.initials: SV
authors.lastname: More
authors.affiliation: Department of Biotechnology, Konkuk University, 380-701, South Korea.
authors.forename: In-Su
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Neurology, School of Medicine, Konkuk University, 380-704, South Korea.
authors.forename: Sang-Don
authors.initials: SD
authors.lastname: Han
authors.affiliation: Department of Biomedical Chemistry, Konkuk University, 380-701, South Korea.
authors.forename: Si-Kwan
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, South Korea.
authors.forename: Sung-Hwa
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: Department of Biotechnology, Konkuk University, 380-701, South Korea. Electronic address: choidk@kku.ac.kr.
authors.forename: Dong-Kug
authors.initials: DK
authors.lastname: Choi
mesh_terms: D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; C012195:asarone
keywords: MPTP; Microglia; Neuroinflammation; Parkinson's disease; α-Asarone