title: Protective effect of madecassoside against cognitive impairment induced by D-galactose in mice.
abstract: This study was designed to investigate the protective effect of madecassoside from Hydrocotyle sibthorpioides against cognitive impairment induced by D-galactose (D-gal) in mice. The result revealed that treatment with madecassoside significantly reversed D-gal-induced learning and memory impairments, as measured by the Morris water-maze test. Studies on the potential mechanisms of this action showed that madecassoside significantly reduced oxidative stress and suppress inflammatory responses via blocking NF-κB and ERK/p38 MAPK pathways. Moreover, madecassoside markedly attenuated the content and deposition of β-amyloid peptide by inducing a decrease in the expression of amyloid protein precursor, β-site amyloid cleaving enzyme-1 and cathepsin B and an increase in the levels of neprilysin and insulin-degrading enzyme. Madecassoside significantly increased the expression of synapse plasticity-related proteins in the hippocampus, such as postsynaptic density 95, long-term potentiation, N-methyl-D-aspartic acid receptors, Ca(2+)/calmodulin-dependent protein kinase II, NMDA receptor subunit 1, protein kinase C, protein kinase A, cAMP-response element binding protein, and brain-derived neurotrophic factor. In addition, madecassoside significantly increased the levels of acetylcholine but decreased cholinesterase activity. In conclusion, the protective effect of madecassoside against d-gal-induced cognitive impairment was mainly due to its ability to reduce oxidative damage, improve synaptic plasticity and restore cholinergic function. These findings suggest that madecassoside can be considered as a potential agent for preventing cognitive impairment.
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Lin
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Renbin
authors.initials: R
authors.lastname: Huang
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Shimei
authors.initials: S
authors.lastname: Tan
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Liang
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Lv
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.affiliation: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
authors.forename: Yuanchun
authors.initials: Y
authors.lastname: Tian
authors.affiliation: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China; Ronald O. Perelman Department of Dermatology, NYU - Langone Medical Center, USA.
authors.forename: Zhongpeng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China. Electronic address: hqf00@126.com.
authors.forename: Quanfang
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D017931:DNA Primers; D005690:Galactose / Q000633:toxicity*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D060888:Real-Time Polymerase Chain Reaction; D014315:Triterpenes / Q000627:therapeutic use*
chemical_list: D017931:DNA Primers; D018836:Inflammation Mediators; D016328:NF-kappa B; D014315:Triterpenes; C093443:madecassoside; D005690:Galactose
keywords: ERK/p38 MAPK; Hydrocotyle sibthorpioides; Madecassoside; Memory impairment; NF-κB; d-Galactose