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Neurochem Res. 2016 Jul;41(7):1806-17. doi: 10.1007/s11064-016-1896-y. Epub 2016 Apr 2.

Natural Xanthones from Garcinia mangostana with Multifunctional Activities for the Therapy of Alzheimer's Disease.

Wang SN1,2,3, Li Q4, Jing MH5, Alba E6, Yang XH1,2,3, Sabaté R6, Han YF7, Pi RB1,2,3,8, Lan WJ9,10,11, Yang XB12, Chen JK13,14,15.

Author information

1
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
2
International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, China.
3
National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-Sen University, Guangzhou, 510080, China.
4
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.
5
Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Zhongshan 2 Rd. 58, Guangzhou, 510080, China.
6
Department de Fisicoquímica, Facultat de Farmàcia, and Institut de Nanociència i Nanotecnologia (IN2UB), Universitat de Barcelona, Av. Joan XXIII, 27-31, 08028, Barcelona, Spain.
7
Department of Applied Biology and Chemical Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
8
Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.
9
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China. lanwj@mail.sysu.edu.cn.
10
International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, China. lanwj@mail.sysu.edu.cn.
11
National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-Sen University, Guangzhou, 510080, China. lanwj@mail.sysu.edu.cn.
12
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.
13
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China. Chenjk3@mail.sysu.edu.cn.
14
International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, China. Chenjk3@mail.sysu.edu.cn.
15
National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-Sen University, Guangzhou, 510080, China. Chenjk3@mail.sysu.edu.cn.

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.

KEYWORDS:

Alzheimer’s disease; Multifunction; Neuroprotection; Oxidative stress; Xanthones

PMID:
27038926
DOI:
10.1007/s11064-016-1896-y
[Indexed for MEDLINE]

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