title: Inhibition of inflammation and oxidative stress by Angelica dahuricae radix extract decreases apoptotic cell death and improves functional recovery after spinal cord injury.
abstract: Inflammation and oxidative stress play major roles in the pathogenesis after spinal cord injury (SCI). Here, we examined the neuroprotective effects of Angelica dahuricae radix (ADR) extract after SCI. ADR extract significantly decreased the levels of proinflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in a lipopolysaccharide (LPS)-activated microglial cell line, BV2 cells. ADR extract also significantly alleviated the level of reactive oxygen species in LPS-activated BV2 cells. To examine the neuroprotective effect of ADR extract after SCI, spinally injured rats were administered ADR extract orally at a dose of 100 mg/kg for 14 days. ADR extract treatment significantly reduced the levels of TNF-α, IL-1β, IL-6, iNOS, and COX-2. The levels of superoxide anion (O(2·)(-)) and protein nitration were also significantly decreased by ADR extract. In addition, ADR extract inhibited p38 mitogen-activated protein kinase activation and pronerve growth factor expression in microglia after SCI. Furthermore, ADR extract significantly inhibited caspase-3 activation following apoptotic cell death of neurons and oligodendrocytes, thereby improving functional recovery after injury. Thus, our data suggest that ADR extract provides neuroprotection by alleviating inflammation and oxidative stress and can be used as an orally administered therapeutic agent for acute SCI.
authors.affiliation: Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul, Korea.
authors.forename: Youn Joo
authors.initials: YJ
authors.lastname: Moon
authors.forename: Jee Youn
authors.initials: JY
authors.lastname: Lee
authors.forename: Myung Sook
authors.initials: MS
authors.lastname: Oh
authors.forename: Youngmi Kim
authors.initials: YK
authors.lastname: Pak
authors.forename: Kang-Sik
authors.initials: KS
authors.lastname: Park
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Oh
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Yune
mesh_terms: D000704:Analysis of Variance; D029969:Angelica / Q000737:chemistry*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001369:Axons / Q000187:drug effects / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D002461:Cell Line, Transformed; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004185:Disability Evaluation; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006614:Hindlimb / Q000503:physiopathology; D020287:In Situ Nick-End Labeling / Q000379:methods; D007211:Indoles; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009186:Myelin Sheath / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy / Q000379:methods*; D028321:Plant Preparations; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000150:complications* / Q000188:drug therapy; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; D007211:Indoles; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D028321:Plant Preparations; D011498:Protein Precursors; D017382:Reactive Oxygen Species; C514218:pro-nerve growth factor, rat; D013481:Superoxides; C018588:Luxol Fast Blue MBS; D009569:Nitric Oxide; D048308:Mitogen-Activated Protein Kinase 14