title: Natural Xanthones from Garcinia mangostana with Multifunctional Activities for the Therapy of Alzheimer's Disease.
abstract: Natural xanthones have diversity pharmacological activities. Here, a series of xanthones isolated from the pericarps of Garcinia mangostana Linn, named α-Mangostin, 8-Deoxygartanin, Gartanin, Garciniafuran, Garcinone C, Garcinone D, and γ-Mangostin were investigated. Biological screening performed in vitro and in Escherichia coli cells indicated that most of the xanthones exhibited significant inhibition of self-induced β-amyloid (Aβ) aggregation and also β-site amyloid precursor protein-cleaving enzyme 1, acted as potential antioxidants and biometal chelators. Among these compounds, α-Mangostin, Gartanin, Garcinone C and γ-Mangostin showed better antioxidant properties to scavenge Diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) free radical than Trolox, and potent neuroprotective effects against glutamate-induced HT22 cell death partly by up-regulating HO-1 protein level and then scavenging reactive oxygen species. Moreover, Gartanin, Garcinone C and γ-Mangostin could be able to penetrate the blood-brain barrier (BBB) in vitro. These findings suggest that the natural xanthones have multifunctional activities against Alzheimer's disease (AD) and could be promising compounds for the therapy of AD.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.|International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, China.|National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, 510120, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Zhongshan 2 Rd. 58, Guangzhou, 510080, China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Jing
authors.affiliation: Department de Fisicoquímica, Facultat de Farmàcia, and Institut de Nanociència i Nanotecnologia (IN2UB), Universitat de Barcelona, Av. Joan XXIII, 27-31, 08028, Barcelona, Spain.
authors.forename: Espargaró
authors.initials: E
authors.lastname: Alba
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.|International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, China.|National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Yang
authors.affiliation: Department de Fisicoquímica, Facultat de Farmàcia, and Institut de Nanociència i Nanotecnologia (IN2UB), Universitat de Barcelona, Av. Joan XXIII, 27-31, 08028, Barcelona, Spain.
authors.forename: Raimon
authors.initials: R
authors.lastname: Sabaté
authors.affiliation: Department of Applied Biology and Chemical Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Han
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.|International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, China.|National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-Sen University, Guangzhou, 510080, China.|Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Rong-Biao
authors.initials: RB
authors.lastname: Pi
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China. lanwj@mail.sysu.edu.cn.|International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, China. lanwj@mail.sysu.edu.cn.|National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-Sen University, Guangzhou, 510080, China. lanwj@mail.sysu.edu.cn.
authors.forename: Wen-Jian
authors.initials: WJ
authors.lastname: Lan
authors.affiliation: The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, 510120, China. yangxiaobomd@163.com.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China. Chenjk3@mail.sysu.edu.cn.|International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, China. Chenjk3@mail.sysu.edu.cn.|National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-Sen University, Guangzhou, 510080, China. Chenjk3@mail.sysu.edu.cn.
authors.forename: Jing-Kao
authors.initials: JK
authors.lastname: Chen
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D029762:Garcinia mangostana; D051379:Mice; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D044004:Xanthones / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016229:Amyloid beta-Peptides; D010936:Plant Extracts; D044004:Xanthones; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse
keywords: Alzheimer’s disease; Multifunction; Neuroprotection; Oxidative stress; Xanthones