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Neurochemical Research

, Volume 41, Issue 7, pp 1806–1817 | Cite as

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

  • Sheng-nan Wang
  • Qian Li
  • Ming-hua Jing
  • Espargaró Alba
  • Xiao-hong Yang
  • Raimon Sabaté
  • Yi-fan Han
  • Rong-biao Pi
  • Wen-jian LanEmail author
  • Xiao-bo YangEmail author
  • Jing-kao ChenEmail author
Original Paper

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

Xanthones Neuroprotection Oxidative stress Alzheimer’s disease Multifunction 

Abbreviations

AD

Alzheimer’s disease

MTDLs

Multi-target-directed ligands

β-Amyloid

BACE1

β-Site amyloid precursor protein-cleaving enzyme 1

DPPH

Diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl

BBB

Blood–brain barrier

HO-1

Heme oxygenase-1

Notes

Acknowledgments

The authors would like to thank Dr. Ling Huang for their technical expertise. This study was supported by Guangdong Provincial International Cooperation Project of Science & Technology (No. 2013B051000038), National Natural Science Foundation of China (No. 31371070) and the Fundamental Research Funds for the Central Universities (No. 15ykjc08b) to R. Pi.

Supplementary material

11064_2016_1896_MOESM1_ESM.tif (548 kb)
S1 Fig.  1H NMR spectrum of α-Mangostin in CDCl3 (300 MHz) (TIFF 548 kb)
11064_2016_1896_MOESM2_ESM.tif (837 kb)
S2 Fig.  13C NMR spectrum of α-Mangostin in CDCl3 (75 MHz) (TIFF 837 kb)
11064_2016_1896_MOESM3_ESM.tif (697 kb)
S3 Fig.  1H NMR spectrum of 8-Deoxygartanin in DMSO-d 6 (300 MHz) (TIFF 697 kb)
11064_2016_1896_MOESM4_ESM.tif (936 kb)
S4 Fig.  13C NMR spectrum of 8-Deoxygartanin in DMSO-d 6 (75 MHz) (TIFF 936 kb)
11064_2016_1896_MOESM5_ESM.tif (612 kb)
S5 Fig.  1H NMR spectrum of Gartanin in DMSO-d 6 (300 MHz) (TIFF 612 kb)
11064_2016_1896_MOESM6_ESM.tif (1 mb)
S6 Fig.  13C NMR spectrum of Gartanin in DMSO-d 6 (75 MHz) (TIFF 1051 kb)
11064_2016_1896_MOESM7_ESM.tif (551 kb)
S7 Fig.  1H NMR spectrum of Garciniafuran in CDCl3 (300 MHz) (TIFF 551 kb)
11064_2016_1896_MOESM8_ESM.tif (1 mb)
S8 Fig.  13C NMR spectrum of Garciniafuran in CDCl3 (75 MHz) (TIFF 1047 kb)
11064_2016_1896_MOESM9_ESM.tif (617 kb)
S9 Fig.  1H NMR spectrum of Garcinone in DMSO-d 6 (300 MHz) (TIFF 616 kb)
11064_2016_1896_MOESM10_ESM.tif (792 kb)
S10 Fig.  13C NMR spectrum of Garcinone in DMSO-d 6 (75 MHz) (TIFF 791 kb)
11064_2016_1896_MOESM11_ESM.tif (637 kb)
S11 Fig.  1H NMR spectrum of Garcinone D in DMSO-d6 (300 MHz) (TIFF 637 kb)
11064_2016_1896_MOESM12_ESM.tif (985 kb)
S12 Fig.  13C NMR spectrum of Garcinone D in DMSO-d6 (75 MHz) (TIFF 985 kb)
11064_2016_1896_MOESM13_ESM.tif (611 kb)
S13 Fig. S13 Fig. 1H NMR spectrum of γ-Mangostin in DMSO-d6 (300 MHz) (TIFF 611 kb)
11064_2016_1896_MOESM14_ESM.tif (906 kb)
S14 Fig.  13C NMR spectrum of γ-Mangostin in DMSO-d6 (75 MHz) (TIFF 906 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Sheng-nan Wang
    • 1
    • 2
    • 3
  • Qian Li
    • 4
  • Ming-hua Jing
    • 5
  • Espargaró Alba
    • 6
  • Xiao-hong Yang
    • 1
    • 2
    • 3
  • Raimon Sabaté
    • 6
  • Yi-fan Han
    • 7
  • Rong-biao Pi
    • 1
    • 2
    • 3
    • 8
  • Wen-jian Lan
    • 1
    • 2
    • 3
    Email author
  • Xiao-bo Yang
    • 4
    Email author
  • Jing-kao Chen
    • 1
    • 2
    • 3
    Email author
  1. 1.School of Pharmaceutical SciencesSun Yat-Sen UniversityGuangzhouChina
  2. 2.International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of GuangdongGuangzhouChina
  3. 3.National and Local United Engineering Lab of Druggability and New Drugs EvaluationSun Yat-Sen UniversityGuangzhouChina
  4. 4.The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine SyndromeGuangzhouChina
  5. 5.Department of Traditional Chinese Medicine, The First Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina
  6. 6.Department de Fisicoquímica, Facultat de Farmàcia, and Institut de Nanociència i Nanotecnologia (IN2UB)Universitat de BarcelonaBarcelonaSpain
  7. 7.Department of Applied Biology and Chemical Technology, Institute of Modern Chinese MedicineThe Hong Kong Polytechnic UniversityHung HomHong Kong, China
  8. 8.Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouChina

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