Natural Xanthones from Garcinia mangostana with Multifunctional Activities for the Therapy of Alzheimer’s Disease
- 923 Downloads
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.
KeywordsXanthones Neuroprotection Oxidative stress Alzheimer’s disease Multifunction
β-Site amyloid precursor protein-cleaving enzyme 1
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.
- 14.Huang HJ, Chen WL, Hsieh RH, Hsieh-Li HM (2014) Multifunctional effects of mangosteen pericarp on cognition in C57BL/6J and triple transgenic Alzheimer’s mice. Evid-Based Complement Altern Med eCAM 2014:813672Google Scholar
- 21.Luo Y, Bolon B, Kahn S, Bennett BD, Babu-Khan S, Denis P, Fan W, Kha H, Zhang J, Gong Y, Martin L, Louis JC, Yan Q, Richards WG, Citron M, Vassar R (2001) Mice deficient in BACE1, the Alzheimer’s beta-secretase, have normal phenotype and abolished beta-amyloid generation. Nat Neurosci 4(3):231–232CrossRefPubMedGoogle Scholar
- 30.Trovato Salinaro A, Cornelius C, Koverech G, Koverech A, Scuto M, Lodato F, Fronte V, Muccilli V, Reibaldi M, Longo A, Uva MG, Calabrese V (2014) Cellular stress response, redox status, and vitagenes in glaucoma: a systemic oxidant disorder linked to Alzheimer’s disease. Front Pharmacol 5:129CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Calabrese V, Cornelius C, Mancuso C, Pennisi G, Calafato S, Bellia F, Bates TE, Giuffrida Stella AM, Schapira T, Dinkova Kostova AT, Rizzarelli E (2008) Cellular stress response: a novel target for chemoprevention and nutritional neuroprotection in aging, neurodegenerative disorders and longevity. Neurochem Res 33(12):2444–2471CrossRefPubMedGoogle Scholar
- 32.Calabrese V, Cornelius C, Dinkova-Kostova AT, Iavicoli I, Di Paola R, Koverech A, Cuzzocrea S, Rizzarelli E (1822) Calabrese EJ (2012) cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity. Biochim Biophys Acta 5:753–783Google Scholar
- 33.Viayna E, Sola I, Bartolini M, De Simone A, Tapia-Rojas C, Serrano FG, Sabate R, Juarez-Jimenez J, Perez B, Luque FJ, Andrisano V, Clos MV, Inestrosa NC, Munoz-Torrero D (2014) Synthesis and multitarget biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents. J Med Chem 57(6):2549–2567CrossRefPubMedGoogle Scholar