Identification of Anti-inflammatory and Antioxidant Properties of MangostinXanthones in Adipocyte Reporter Assays

We developed three fluorescence biosensors based on a 3T3-L1 cell line that stably expressed nuclear factor κB response element (<i>Nfkb</i>-RE)/GFP, fatty acid binding protein 4 promoter (<i>Fabp4</i>-P)/CFP, and nuclear factor erythroid 2-related factor2 promoter (<i>Nrf2</i>-P)/YFP fluorescent reporters. We hypothesized that fluorescent signals directly correlated to inflammatory, adipogenic, and antioxidant status in adipocytes, respectively. Two polyphenolic xanthones, α-mangostin (α-MG) and γ-mangostin (γ-MG) from mangosteen fruit, have been reported to have anti-adipogenic and anti-inflammatory activities. We validated inflammatory and adipogenic properties of the major mangosteen xanthone α-MG using a <i>Nfkb</i>-RE/GFP biosensor assay, traditional ELISA, and semi-quantitative PCR approach. We also identified unique properties of γ-MG, a minor xanthone in mangosteen fruit. γ-MG suppressed adipogenesis and the anti-inflammatory cytokine adiponectin, but retained its ability to suppress the <i>Nfkb</i>-RE/GFP reporter and reduced the secretion of MCP-1 as compared to control adipocytes. To gain insight into mechanisms involved in the inhibition of adipogenesis, we compared the effects of α-MG on the activation of PPARγ and its target gene <i>Fabp4</i>, and Nrf2, an inducer of <i>Pparg</i> expression. The screening in <i>Nrf2</i>-P/YFP adipocytes suggested that α-MG effectively and dose-dependently reduced <i>Nrf2</i> promoter activation, whereas <i>Fabp4</i> promoter activation was not influenced. Thus, the antioxidant response of α-MG appears to be an early mechanism for the suppression of adipogenic and inflammatory effects in adipocytes. The combined application of high-throughput fluorescence biosensors can provide an effective platform for the identification of nutraceuticals and the mechanism of their actions in adipocytes.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Human Ecology: Human Nutrition

Grantor dc:publisher

The Ohio State University

Year dc:date

2013

Author dc:creator

• Shen, Qiwen

Contributors dc:contributor

• Ziouzenkova, Ouliana

• Nutrition
• adipocyte
• anti-inflammation
• mangostin
• Nrf2
• obesity

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=osu1366099986

OAI identifier oai:identifier

oai:etd.ohiolink.edu:osu1366099986