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Alpha-mangostin inhibits viral replication and suppresses nuclear factor kappa B (NF-κB)-mediated inflammation in dengue virus infection.

ABSTRACT: Severe dengue virus (DENV) infection results from viral replication and dysregulated host immune response, which trigger massive cytokine production/cytokine storm. The result is severe vascular leakage, hemorrhagic diathesis, and organ dysfunction. Subsequent to previously proposing that an ideal drug for treatment of DENV infection should efficiently inhibit both virus production and cytokine storm, we discovered that α-mangostin (α-MG) from the pericarp of the mangosteen fruit could inhibit both DENV infection and cytokine/chemokine production. In this study, we investigated the molecular mechanisms underlying the antiviral and anti-inflammatory effects of α-MG. Time-of-drug-addition and time-of-drug-elimination studies suggested that α-MG inhibits the replication step of the DENV life cycle. α-MG inhibited polymerization activity of RNA-dependent RNA polymerase (RdRp) with IC50 values of 16.50 μM and significantly reduced viral RNA and protein syntheses, and virion production. Antiviral and cytokine/chemokine gene expression profiles of α-MG-treated DENV-2-infected cells were investigated by polymerase chain reaction array. α-MG suppressed the expression of 37 antiviral and cytokine/chemokine genes that relate to the NF-κB signaling pathway. Immunofluorescence and immunoblot analyses revealed that α-MG inhibits NF-κB nuclear translocation in DENV-2-infected cells in association with reduced RANTES, IP-10, TNF-α, and IL-6 production. These results suggest α-MG as a potential treatment for DENV infection.

SUBMITTER: Tarasuk M

PROVIDER: S-EPMC9515165 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Alpha-mangostin inhibits viral replication and suppresses nuclear factor kappa B (NF-κB)-mediated inflammation in dengue virus infection.

Tarasuk Mayuri M Songprakhon Pucharee P Chieochansin Thaweesak T Choomee Kornkan K Na-Bangchang Kesara K Yenchitsomanus Pa-Thai PT

Scientific reports 20220927 1

Severe dengue virus (DENV) infection results from viral replication and dysregulated host immune response, which trigger massive cytokine production/cytokine storm. The result is severe vascular leakage, hemorrhagic diathesis, and organ dysfunction. Subsequent to previously proposing that an ideal drug for treatment of DENV infection should efficiently inhibit both virus production and cytokine storm, we discovered that α-mangostin (α-MG) from the pericarp of the mangosteen fruit could inhibit b ...[more]

PMID: 36168031

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Project description:This study aimed to explore the effects of plumbagin on rheumatoid arthritis (RA) and its mechanism. The RA cell model was simulated following the treatment of interleukin-1β (IL-1β). After the treatment of various concentrations of plumbagin, the impact of plumbagin on the cell viability was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The collagen-induced arthritis (CIA) model was established using the solution of bovine type II collagen. Hematoxylin-eosin staining was used to observe the changes of ankle joint tissue, while enzyme-linked immunosorbent assay and western blot were applied to detect the level of inflammatory cytokines. Plumbagin inhibited the viability of human fibroblast-like synoviocytes (HFLS) at the concentration of 1 ~ 3.5 μM. The inhibitory effect of 1 μM plumbagin on cell proliferation was similar to that of methotrexate, the drug used as the positive control. Plumbagin downregulated the levels of inflammatory cytokines and matrix metalloproteinases (MMPs) in IL-1β-treated HFLS, and suppressed the activation of IκB and nuclear factor kappa-B (NF-κB) as well as the entry of p65 into the nucleus. It was also demonstrated in animal experiments that plumbagin inhibited the activation of NF-κB pathway, down-regulated the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and MMPs, and alleviated joint damage in CIA-modeled mice. Collectively speaking, plumbagin might down-regulate the levels of inflammatory cytokines and MMPs through inhibiting the activation of the NF-κB pathway, thereby attenuating RA-induced damage to cells and joints.Abbreviations: CIA: Collagen-induced arthritis; ELISA: Enzyme-linked immuno sorbent assay; HFLS: Human fibroblast-like synoviocytes; IL-6: Interleukin-6; IL-1β: Interleukin-1β; NF-κB: nuclear factor kappa-B; MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; MMPs: Matrix metalloproteinase; OD: Optical density; RA: Rheumatoid arthritis; SDS: Sodium dodecyl sulfate; SD: Standard deviation; TNF-α: Tumor necrosis factor-α; PVDF: Polyvinylidene fluoride.

Dataset Information

Alpha-mangostin inhibits viral replication and suppresses nuclear factor kappa B (NF-κB)-mediated inflammation in dengue virus infection.

Publications

Alpha-mangostin inhibits viral replication and suppresses nuclear factor kappa B (NF-κB)-mediated inflammation in dengue virus infection.

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