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Virus Res. 2017 Aug 15;240:180-189. doi: 10.1016/j.virusres.2017.08.011. Epub 2017 Aug 31.

Alpha-mangostin inhibits both dengue virus production and cytokine/chemokine expression.

Author information

1
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, 12121, Thailand.
2
Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
3
Research Division, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; Center for Emerging and Neglected Infectious Disease, Mahidol University, Bangkok 73170, Thailand.
4
Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. Electronic address: pathai.yen@mahidol.ac.th.

Abstract

Since severe dengue virus (DENV) infection in humans associates with both high viral load and massive cytokine production - referred to as "cytokine storm", an ideal drug for treatment of DENV infection should efficiently inhibit both virus production and cytokine expression. In searching for such an ideal drug, we discovered that α-mangostin (α-MG), a major bioactive compound purified from the pericarp of the mangosteen fruit (Garcinia mangostana Linn), which has been used in traditional medicine for several conditions including trauma, diarrhea, wound infection, pain, fever, and convulsion, inhibits both DENV production in cultured hepatocellular carcinoma HepG2 and Huh-7 cells, and cytokine/chemokine expression in HepG2 cells. α-MG could also efficiently inhibit all four serotypes of DENV. Treatment of DENV-infected cells with α-MG (20μM) significantly reduced the infection rates of four DENV serotypes by 47-55%. α-MG completely inhibited production of DENV-1 and DENV-3, and markedly reduced production of DENV-2 and DENV-4 by 100 folds. Furthermore, it could markedly reduce cytokine (IL-6 and TNF-α) and chemokine (RANTES, MIP-1β, and IP-10) transcription. These actions of α-MG are more potent than those of antiviral agent (ribavirin) and anti-inflammatory drug (dexamethasone). Thus, α-MG is potential to be further developed as therapeutic agent for DENV infection.

KEYWORDS:

Anti-inflammatory; Antiviral compound; Chemokine; Cytokine; Dengue virus; α-Mangostin

PMID:
28864423
DOI:
10.1016/j.virusres.2017.08.011
[Indexed for MEDLINE]

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