title: Neuroprotective effect of loganin against Aβ25-35-induced injury via the NF-κB-dependent signaling pathway in PC12 cells.
abstract: Amyloid-beta (Aβ) protein, the main constituent of senile plaques, is believed to play a pivotal role in the pathogenesis of Alzheimer's disease (AD). AD is closely associated with inflammatory reactions which are considered to be responses to Aβ deposition. The present study investigated the effect of loganin on Aβ25-35-induced inflammatory damage and the underlying molecular mechanism of its neuroprotective action. Loganin predominantly prevented Aβ25-35-stimulated cell death through suppressing ROS generation, and attenuating apoptosis by inhibiting caspase-3 activity and regulating cell cycle. Furthermore, loganin suppressed the level of TNF-α and protein expression of iNOS and COX-2 in Aβ25-35-injured PC12 cells. These inhibitions appeared to correlate with the suppression of NF-κB activation by loganin, as pre-treating cells with loganin blocked the translocation of NF-κB into the nuclear compartment and degradation of the inhibitory subunit IκB. Loganin substantially inhibited phosphorylation of MAPKs including ERK1/2, p38 and JNK, which are closely related to regulation of NF-κB activation. Taken together, the results implied that loganin attenuated neuroinflammatory responses through the inactivation of NF-κB by NF-κB dependent inflammatory pathways and phosphorylation of MAPK in Aβ25-35-induced PC12 cells.
authors.affiliation: Department of Food Science and Nutrition, Dong-A University, Busan 604-714, Korea. mjun@dau.ac.kr.
authors.forename: Hyeri
authors.initials: H
authors.lastname: Kim
authors.forename: Kumju
authors.initials: K
authors.lastname: Youn
authors.forename: Mok-Ryeon
authors.initials: MR
authors.lastname: Ahn
authors.forename: Oh Yoen
authors.initials: OY
authors.lastname: Kim
authors.forename: Woo-Sik
authors.initials: WS
authors.lastname: Jeong
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.forename: Mira
authors.initials: M
authors.lastname: Jun
mesh_terms: D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D039823:Iridoids / Q000494:pharmacology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000009:adverse effects*; D010766:Phosphorylation; D051381:Rats; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D039823:Iridoids; D016328:NF-kappa B; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C074636:amyloid beta-protein (25-35); D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D048052:Mitogen-Activated Protein Kinase 3; C505410:Casp3 protein, rat; D053148:Caspase 3; C059516:loganin