title: Humulus japonicus inhibits the progression of Alzheimer's disease in a APP/PS1 transgenic mouse model.
abstract: Humulus japonicus Siebold & Zucc. (HJ) has traditionally been administered to patients with pulmonary disease, skin disease and hypertension in Korea, and it is considered to exert anti-inflammatory, antioxidant, antimicrobial and antimycobacterial effects. However, its effects against Alzheimer's disease (AD) have yet to be explored. Thus, this study was carried out to investigate whether HJ has a beneficial effect on the progression of AD in an animal model. A methanolic extract of HJ (500 mg/kg/day) was intragastrically administered to 5-month-old APP/PS1 transgenic (Tg-APP/PS1) mice for 2.5 months. Novel object recognition and Y-maze alteration tests were used to assess cognitive function, and an immunohistochemical assay was performed to assess amyloid β (Aβ)deposition, tau phosphorylation and gliosis. An in vitro assay using a microglial cell line was also performed to investigate the anti-inflammatory effects of HJ. Our results revealed that HJ significantly decreased the mRNA and protein expression levels of tumor necrosis factor-α (TNF‑α), interleukin (IL)-1β, IL-6 and inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide in the microglial cell line. The administration of HJ for 2 months improved the cognitive function of Tg-APP/PS1 mice. HJ notably reduced the area occupied by Aβ and neurofibrillary tangles, and the number of activated astrocytes and microglia in the cortex of Tg-APP/PS1 mice. The findings of our study suggest that HJ has the therapeutic potential to inhibit the progression of AD and to improve cognitive deterioration in Tg-APP/PS1 mice.
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Tae-Shin
authors.initials: TS
authors.lastname: Park
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Young-Kyoung
authors.initials: YK
authors.lastname: Ryu
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Hye-Yeon
authors.initials: HY
authors.lastname: Park
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Jae Yun
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Go
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Jung-Ran
authors.initials: JR
authors.lastname: Noh
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Dong-Hee
authors.initials: DH
authors.lastname: Choi
authors.affiliation: Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Won-Keun
authors.initials: WK
authors.lastname: Oh
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Kyoung-Shim
authors.initials: KS
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D003071:Cognition / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005106:Exploratory Behavior / Q000187:drug effects; D006801:Humans; D027582:Humulus / Q000737:chemistry*; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007339:Insulysin; D008070:Lipopolysaccharides; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D053764:Presenilin-1 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010936:Plant Extracts; D053764:Presenilin-1; D012333:RNA, Messenger; D016875:tau Proteins; D009569:Nitric Oxide; D007339:Insulysin