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

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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.

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Abbreviations

AD:

Alzheimer’s disease

MTDLs:

Multi-target-directed ligands

Aβ:

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

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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.

Author information

Author notes

    Authors and Affiliations

    1. School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China

      Sheng-nan Wang, Xiao-hong Yang, Rong-biao Pi, Wen-jian Lan & Jing-kao Chen

    2. International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, China

      Sheng-nan Wang, Xiao-hong Yang, Rong-biao Pi, Wen-jian Lan & Jing-kao Chen

    3. National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-Sen University, Guangzhou, 510080, China

      Sheng-nan Wang, Xiao-hong Yang, Rong-biao Pi, Wen-jian Lan & Jing-kao Chen

    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

      Qian Li & Xiao-bo Yang

    5. Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Zhongshan 2 Rd. 58, Guangzhou, 510080, China

      Ming-hua Jing

    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

      Espargaró Alba & Raimon Sabaté

    7. Department of Applied Biology and Chemical Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China

      Yi-fan Han

    8. Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China

      Rong-biao Pi

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    1. Sheng-nan Wang
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    Corresponding authors

    Correspondence to Wen-jian Lan, Xiao-bo Yang or Jing-kao Chen.

    Additional information

    Sheng-nan Wang, Qian Li and Ming-hua Jing have equally contributed to this work.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    S1 Fig. 

    1H NMR spectrum of α-Mangostin in CDCl3 (300 MHz) (TIFF 548 kb)

    S2 Fig. 

    13C NMR spectrum of α-Mangostin in CDCl3 (75 MHz) (TIFF 837 kb)

    S3 Fig. 

    1H NMR spectrum of 8-Deoxygartanin in DMSO-d 6 (300 MHz) (TIFF 697 kb)

    S4 Fig. 

    13C NMR spectrum of 8-Deoxygartanin in DMSO-d 6 (75 MHz) (TIFF 936 kb)

    S5 Fig. 

    1H NMR spectrum of Gartanin in DMSO-d 6 (300 MHz) (TIFF 612 kb)

    S6 Fig. 

    13C NMR spectrum of Gartanin in DMSO-d 6 (75 MHz) (TIFF 1051 kb)

    S7 Fig. 

    1H NMR spectrum of Garciniafuran in CDCl3 (300 MHz) (TIFF 551 kb)

    S8 Fig. 

    13C NMR spectrum of Garciniafuran in CDCl3 (75 MHz) (TIFF 1047 kb)

    S9 Fig. 

    1H NMR spectrum of Garcinone in DMSO-d 6 (300 MHz) (TIFF 616 kb)

    S10 Fig. 

    13C NMR spectrum of Garcinone in DMSO-d 6 (75 MHz) (TIFF 791 kb)

    S11 Fig. 

    1H NMR spectrum of Garcinone D in DMSO-d6 (300 MHz) (TIFF 637 kb)

    S12 Fig. 

    13C NMR spectrum of Garcinone D in DMSO-d6 (75 MHz) (TIFF 985 kb)

    S13 Fig.

    S13 Fig. 1H NMR spectrum of γ-Mangostin in DMSO-d6 (300 MHz) (TIFF 611 kb)

    S14 Fig. 

    13C NMR spectrum of γ-Mangostin in DMSO-d6 (75 MHz) (TIFF 906 kb)

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    Wang, Sn., Li, Q., Jing, Mh. et al. Natural Xanthones from Garcinia mangostana with Multifunctional Activities for the Therapy of Alzheimer’s Disease. Neurochem Res 41, 1806–1817 (2016). https://doi.org/10.1007/s11064-016-1896-y

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