title: Bee venom ameliorates lipopolysaccharide-induced memory loss by preventing NF-kappaB pathway.
abstract: BACKGROUND
  Accumulation of beta-amyloid and neuroinflammation trigger Alzheimer's disease. We previously found that lipopolysaccharide (LPS) caused neuroinflammation with concomitant accumulation of beta-amyloid peptides leading to memory loss. A variety of anti-inflammatory compounds inhibiting nuclear factor kappaB (NF-κB) activation have showed efficacy to hinder neuroinflammation and amyloidogenesis. We also found that bee venom (BV) inhibits NF-κB.
  
  
  METHODS
  A mouse model of LPS-induced memory loss used administration of BV (0.8 and 1.6 μg/kg/day, i.p.) to ICR mice for 7 days before injection of LPS (2.5 mg/kg/day, i.p.). Memory loss was assessed using a Morris water maze test and passive avoidance test. For in vitro study, we treated BV (0.5, 1, and 2 μg/mL) to astrocytes and microglial BV-2 cells with LPS (1 μg/mL).
  
  
  RESULTS
  We found that BV inhibited LPS-induced memory loss determined by behavioral tests as well as cell death. BV also inhibited LPS-induced increases in the level of beta-amyloid (Aβ), β-and γ-secretases activities, NF-κB and its DNA-binding activity and expression of APP, and BACE1 and neuroinflammation proteins (COX-2, iNOS, GFAP and IBA-1) in the brain and cultured cells. In addition, pull-down assay and molecular modeling showed that BV binds to NF-κB.
  
  
  CONCLUSIONS
  BV attenuates LPS-induced amyloidogenesis, neuroinflammation, and therefore memory loss via inhibiting NF-κB signaling pathway. Thus, BV could be useful for treatment of Alzheimer's disease.
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaemgmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk, 361-951, Republic of Korea.
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Gu
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaemgmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk, 361-951, Republic of Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Park
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaemgmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk, 361-951, Republic of Korea.
authors.forename: Chul Ju
authors.initials: CJ
authors.lastname: Hwang
authors.affiliation: College of Oriental Medicine, Gachon University, San 65, Bokjeong-dong, Sujeong-gu, Seongnam, Gyeonggii-do, 461-701, Republic of Korea.
authors.forename: Ho Sueb
authors.initials: HS
authors.lastname: Song
authors.affiliation: Department of Food Science & Technology, Korea National University of Transportation, Jeungpyeong, 368-701, Republic of Korea.
authors.forename: Ung Soo
authors.initials: US
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaemgmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk, 361-951, Republic of Korea.
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaemgmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk, 361-951, Republic of Korea.
authors.forename: Ki Wan
authors.initials: KW
authors.lastname: Oh
authors.affiliation: Department of Chemistry, Utah Valley University, 800 W University Pkwy, Orem, UT, 84058, USA.
authors.forename: Young Wan
authors.initials: YW
authors.lastname: Ham
authors.affiliation: Department of Obstetrics and Gynecology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 64 Daeheung-ro, Jung gu, Daejeon, 301-723, Republic of Korea.
authors.forename: Min Jong
authors.initials: MJ
authors.lastname: Song
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaemgmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk, 361-951, Republic of Korea. sondj1@chungbuk.ac.kr.
authors.forename: Dong Ju
authors.initials: DJ
authors.lastname: Son
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaemgmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk, 361-951, Republic of Korea. jinthong@chungbuk.ac.kr.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001514:Bee Venoms / Q000494:pharmacology* / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D001514:Bee Venoms; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2