Program

PO1-9-20

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

[Speaker] Mayuri Tarasuk:1
[Co-author] Pucharee Songprakhon:2, Pa-Thai Yenchitsomanus:2, Kesara Na-Bangchang:1
1:Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand, 2:Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

Background
Dengue virus (DENV) infection is a global public health problem. The severity of the disease in patients with dengue infection correlates with high viral load and excessive immune activation which creates a cascade of cytokine production, called "cytokine storm". Secondary infections are considered a risk factor for developing severe dengue, presumably through a mechanism called antibody-dependent enhancement (ADE). Currently, neither a preventive vaccine nor an effective therapeutic agent is available. Thus, inhibition of DENV and cytokine production could be expected to enhance therapeutic effects for DENV infection.

Methods
In this work, the effect of alpha-mangostin (alpha-MG) from Garcinia mangostana Linn. treatment on dengue virus infection and cytokine production in hepatocellular carcinoma HepG2 and U937-derived macrophages was evaluated.

Results
Alpha-MG effectively inhibited dengue virus infection in both cell lines. Treatment of dengue infected cells with alpha-MG significantly reduced cell infection rates and viral release into the culture supernatant. Moreover, alpha-MG effectively reduced cytokine (IL-6 and TNF-alpha) and chemokine (RANTES, MIP-1beta, and IP-10) production in infected HepG2 cells. Alpha-MG could also efficiently reduced cytokine (IL-1beta, IL-6, and IL-10) and chemokine (IP-10) in ADE-DENV-infected cells.

Conclusions
Our results demonstrated that alpha-MG efficiently inhibits both DENV and cytokine/chemokine production in DENV-infected cells. The combined antiviral and
anti-inflammatory properties of alpha-MG signify the potential of further development as an antiviral chemotherapy to control the spread of the virus and to prevent the complications associated with DENV and immunopathologic responses to DENV infection.

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