title: Attenuation of neuroinflammatory responses and behavioral deficits by Ligusticum officinale (Makino) Kitag in stimulated microglia and MPTP-induced mouse model of Parkinson's disease.
abstract: BACKGROUND
  Ligusticum officinale (Makino) Kitag (L. officinale) is one of the important traditional herbs used in traditional Oriental medicine for the treatment of various disorders including pain and inflammation. However, there is limited scientific basis for its activity and mechanism in brain inflammation.
  
  
  OBJECTIVE
  This study aimed to evaluate the effects of L. officinale on microglia-mediated neuroinflammation and behavioral impairments using in vitro cellular and in vivo mouse model of PD, as well as investigate the molecular mechanisms involved including the finger printing analysis of its ethanol extract.
  
  
  METHODS
  Lipopolysaccharide (LPS) was used to stimulate BV-2 microglial cells. The changes in neuroinflammatory expressional levels were measured by Western blotting and immunofluorescence techniques. 1-methyl-4 phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-intoxicated mice model of PD was developed to evaluate the behavioral impairments and the brain tissues were used for immunohistochemical studies. High performance liquid chromatography (HPLC) technique was performed for finger printing analysis of L. officinale extract used in the study.
  
  
  RESULTS
  L. officinale significantly attenuated the LPS-stimulated increase in inflammatory mediators in BV-2 cells. L. officinale also inhibited the LPS-induced activation of nuclear factor-kappa beta by blocking the degradation of IκB-α and suppressing the increase in p38-mitogen-activated protein kinase phosphorylation in BV-2 cells. Furthermore, L. officinale exhibited significant antioxidant properties by inhibiting the 1-diphenyl-2-picrylhydrazyl radicals. An in vivo evaluation in MPTP (20mg/kg, four times, 1 day, i.p.) intoxicated mice resulted in brain microglial activation and significant behavioral deficits. Prophylactic treatment with L. officinale prevented microglial activation and attenuated PD-like behavioral changes as assessed by the pole test. HPLC finger printing analysis revealed that L. officinale extract contained ferulic acid (FA) as one of the major constituents compared with reference standard. FA also inhibited the LPS-stimulated excessive release of NO and suppressed the increased the expressional levels of proinflammatory mediators in BV-2 microglia.
  
  
  CONCLUSIONS
  The findings observed in this study indicated that L. officinale extract significantly attenuated the neuroinflammatory processes in stimulated microglia and restored the behavioral impairments in a mouse model of PD providing a scientific basis for its traditional claims.
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju, Korea.
authors.forename: Byung-Wook
authors.initials: BW
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju, Korea.
authors.forename: Sushruta
authors.initials: S
authors.lastname: Koppula
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju, Korea.
authors.forename: Shin-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju, Korea.
authors.forename: Yon-Suk
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju, Korea.
authors.forename: Pyo-Jam
authors.initials: PJ
authors.lastname: Park
authors.affiliation: Department of Biomedical chemistry, Konkuk University, Chungju, Korea.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju, Korea.
authors.forename: In-Su
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju, Korea. Electronic address: choidk@kku.ac.kr.
authors.forename: Dong-Kug
authors.initials: DK
authors.lastname: Choi
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein; D030004:Ligusticum; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D016177:Macrophage-1 Antigen; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010936:Plant Extracts; D012333:RNA, Messenger; C528900:glial fibrillary astrocytic protein, mouse; D009569:Nitric Oxide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases
keywords: Ferulic acid; Ligusticum officinale Makino; MPTP; Microglia; Neuroinflammation; Parkinson׳s disease