title: Isorhynchophylline improves learning and memory impairments induced by D-galactose in mice.
abstract: Isorhynchophylline (IRN), an alkaloid isolated from Uncaria rhynchophylla, has been reported to improve cognitive impairment induced by beta-amyloid in rats. However, whether IRN could also ameliorate the D-galactose (D-gal)-induced mouse memory deficits is still not clear. In the present study, we aimed to investigate whether IRN had potential protective effect against the D-gal-induced cognitive deficits in mice. Mice were given a subcutaneous injection of D-gal (100mg/kg) and orally administered IRN (20 or 40mg/kg) daily for 8weeks, followed by assessing spatial learning and memory function by the Morris water maze test. The results showed that IRN significantly improved spatial learning and memory function in the D-gal-treated mice. In the mechanistic studies, IRN significantly increased the level of glutathione (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT), while decreased the level of malondialdehyde (MDA) in the brain tissues of the D-gal-treated mice. Moreover, IRN (20 or 40mg/kg) significantly inhibited the production of prostaglandin E 2 (PGE2) and nitric oxide (NO), and the mRNA expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), as well as the activation of nuclear factor kappa B (NF-κB) in the brain tissues of D-gal-treated mice. Our results amply demonstrated that IRN was able to ameliorate cognitive deficits induced by D-gal in mice, and the observed cognition-improving action may be mediated, at least in part, through enhancing the antioxidant status and anti-inflammatory effect of brain tissues via NFκB signaling.
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Xian
authors.affiliation: College of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Zi-Ren
authors.initials: ZR
authors.lastname: Su
authors.affiliation: College of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Jian-Nan
authors.initials: JN
authors.lastname: Chen
authors.affiliation: College of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Lai
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
authors.forename: Qing-Qiu
authors.initials: QQ
authors.lastname: Mao
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
authors.forename: Christopher H K
authors.initials: CH
authors.lastname: Cheng
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China. Electronic address: paulip@cuhk.edu.hk.
authors.forename: Siu-Po
authors.initials: SP
authors.lastname: Ip
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China. Electronic address: linzx@cuhk.edu.hk.
authors.forename: Zhi-Xiu
authors.initials: ZX
authors.lastname: Lin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005690:Galactose / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D026121:Indole Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism; D000078183:Oxindoles; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D032070:Uncaria / Q000737:chemistry*
chemical_list: D026121:Indole Alkaloids; D000078183:Oxindoles; D009569:Nitric Oxide; C052714:rhyncophylline; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D015232:Dinoprostone; D005690:Galactose
keywords: D-galactose; Isorhynchophylline; Learning and memory impairments; Neuroinflammation; Nuclear factor kappa B; Oxidative stress