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01-04-2019 | ORIGINAL ARTICLE

Metabolomics Analysis Reveals Therapeutic Effects of α-Mangostin on Collagen-Induced Arthritis in Rats by Down-regulating Nicotinamide Phosphoribosyltransferase

Authors: Kui Yang, Qin Yin, Qingcheng Mao, Sheng Dai, Lin Wang, Jiyang Dong, Jian Zuo

Published in: Inflammation | Issue 2/2019

Abstract

α-Mangostin (MAN) is a bioactive compound isolated from pericarp of mangosteen (Garcinia mangostana Linn.) with significant anti-rheumatic potentials. The purpose of this study was to explore the mechanisms underlying its therapeutic effects on collagen-induced arthritis (CIA) in rats with metabolomics approaches. Therapeutic effects of MAN on CIA were assessed by radiographic, histological, and immunohistochemical methods. Metabolic profiles of rats were characterized based on UPLC-MS/MS analysis of urine samples, followed by verification in HFLS-RA cells using a variety of toxicological and biochemical assays. We found that MAN treatment protected joint structures in CIA rats and caused a decrease of nicotinamide mononucleotide (NMN) in urine. The levels of nicotinamide phosphoribosyltransferase (NAMPT) were reduced in fibroblast-like synoviocytes by MAN both in vivo and in vitro, which was accompanied with a decline in nicotinamide adenine dinucleotide (NAD) production. Secretion of extracellular NAMPT (eNAMPT) in HFLS-RA cells was also decreased upon MAN treatment, which lagged behind the changes of its intracellular counterpart (iNAMPT). Co-treatment with NMN raised the secretion of eNAMPT and restored the decline of p-p65 and TNF-α induced by MAN in vitro. Sirt1 expression was down-regulated under MAN treatments too. These results suggest that MAN treatment suppressed NAD production by inhibiting iNAMPT expression, which in turn decreased eNAMPT secretion and alleviated NF-κB-mediated inflammations in CIA rats.

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Title: Metabolomics Analysis Reveals Therapeutic Effects of α-Mangostin on Collagen-Induced Arthritis in Rats by Down-regulating Nicotinamide Phosphoribosyltransferase
Authors: Kui Yang
Qin Yin
Qingcheng Mao
Sheng Dai
Lin Wang
Jiyang Dong
Jian Zuo
Publication date: 01-04-2019
Publisher: Springer US
Published in: Inflammation / Issue 2/2019
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-018-0932-2

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Metabolomics Analysis Reveals Therapeutic Effects of α-Mangostin on Collagen-Induced Arthritis in Rats by Down-regulating Nicotinamide Phosphoribosyltransferase

Abstract

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