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Inflammation

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

  • Kui Yang
  • Qin Yin
  • Qingcheng Mao
  • Sheng Dai
  • Lin Wang
  • Jiyang Dong
  • Jian ZuoEmail author
ORIGINAL ARTICLE
  • 63 Downloads

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.

KEY WORDS

xanthone rheumatoid arthritis NAD metabolism inflammation 

Notes

Funding

This work was supported by the National Natural Science Foundation of China (81603388), Research Project on Traditional Chinese medicine of Anhui province (2016zy37), Key Project of Natural Science Foundation of Anhui Province for College Scholar (KJ2018A0249), and Project of Construction on Key Discipline of State Administration of Traditional Chinese Medicine (2012-32).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The animal experimental protocols were approved by Ethical Committee of Yijishan Hospital and strictly in accordance with the guideline for the care and use of laboratory animals (US National Research Council, 2011).

Supplementary material

10753_2018_932_FIG8_ESM.png (214 kb)
Supplementary S1

Multivariate statistical analyses of metabolic characters of urine samples. Above, PCA; below, OPLS-DA. (PNG 214 kb)

10753_2018_932_MOESM1_ESM.tif (914 kb)
High Resolution Image (TIF 913 kb)
10753_2018_932_MOESM2_ESM.jpg (671 kb)
Supplementary S2 Heat-map of discriminating metabolites between MAN and CIA groups discovered under positive mode. (JPG 671 kb)
10753_2018_932_MOESM3_ESM.jpg (961 kb)
Supplementary S3 Altered metabolic pathways in CIA rats by MAN revealed under positive mode based on pathway enrichment analysis. (JPG 960 kb)
10753_2018_932_MOESM4_ESM.xlsx (237 kb)
Supplementary S4 Statistical analysis of discriminating metabolites between MAN and CIA group discovered under negative mode. (XLSX 237 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Yijishan Hospital of Wannan Medical CollegeWuhuChina
  2. 2.The Second Affiliated Hospital of Wannan Medical CollegeWuhuChina
  3. 3.Department of PharmaceuticsSchool of Pharmacy, University of WashingtonSeattleUSA
  4. 4.Anhui College of Traditional Chinese MedicineWuhuChina
  5. 5.Department of Electronic ScienceXiamen UniversityXiamenChina

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