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Published on: November 28, 2015
α-Mangostin Inhibited M1 Polarization of Macrophages/Monocytes in Antigen-Induced Arthritis Mice by Up-Regulating
Yi-Jin Wu1,2,3, Sa-Sa Zhang1, Qin Yin1
1Department of Pharmacy, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000, People's Republic of China.
Background:
α-Mangostin (MG) showed the potentials in alleviating experimental arthritis, inhibiting inflammatory polarization of macrophages/monocytes, and regulating peroxisome proliferators-activated receptor γ (PPAR-γ) and silent information regulator 1 (SIRT1) signals. The aim of this study was to analyze the correlations among the above-mentioned properties.
Methods:
Antigen-induced arthritis (AIA) was established in mouse, which was treated with MG in combination with SIRT1/PPAR-γ inhibitors to clarify the role of the two signals in the anti-arthritic actions. Pathological changes were systematically investigated. Phenotypes of cells were investigated by flow cytometry. Expression and co-localization of SIRT1 and PPAR-γ proteins in joint tissues were observed by the immunofluorescence method. Finally, clinical implications from the synchronous up-regulation of SIRT1 and PPAR-γ were validated by experiments in vitro.
Results:
SIRT1 and PPAR-γ inhibitors (nicotinamide and T0070097) reduced the therapeutic effects of MG on AIA mice, and abrogated MG-induced up-regulation of SIRT1/PPAR-γ and inhibition of M1 polarization in macrophages/monocytes. MG has a good binding affinity to PPAR-γ, and MG promoted the co-expression of SIRT1 and PPAR-γ in joints. Synchronously activating SIRT1 and PPAR-γ was revealed to be necessary by MG to repress inflammatory responses in THP-1 monocytes.
Conclusion:
MG binds PPAR-γ and excites this signaling to initiate ligand-dependent anti-inflammatory activity. Due to certain unspecified signal transduction crosstalk mechanism, it then promoted SIRT1 expression and further limited inflammatory polarization of macrophages/monocytes in AIA mice.
Insights
α-Mangostin (MG) alleviates arthritis by activating PPAR-γ and SIRT1 pathways, reducing macrophage inflammation. This study clarifies MG
Area of Science:
- Immunology
- Pharmacology
- Molecular Biology
Background:
- α-Mangostin (MG) demonstrates potential in experimental arthritis, modulating macrophage polarization and regulating SIRT1 and PPAR-γ signaling.
- Understanding the interplay between MG, SIRT1, and PPAR-γ is crucial for developing novel anti-arthritic therapies.
Purpose of the Study:
- To investigate the correlations between MG's anti-arthritic effects, macrophage polarization, and the SIRT1/PPAR-γ signaling pathways.
- To elucidate the specific roles of SIRT1 and PPAR-γ in MG's therapeutic actions against experimental arthritis.
Main Methods:
- Antigen-induced arthritis (AIA) model in mice treated with MG and SIRT1/PPAR-γ inhibitors.
- Flow cytometry for cell phenotype analysis and immunofluorescence for protein expression and co-localization.
- In vitro experiments to validate clinical implications of synchronous SIRT1 and PPAR-γ activation.
Main Results:
- SIRT1 and PPAR-γ inhibitors diminished MG's therapeutic effects in AIA mice, blocking MG-induced SIRT1/PPAR-γ upregulation and M1 macrophage polarization inhibition.
- MG exhibits binding affinity for PPAR-γ and promotes co-expression of SIRT1 and PPAR-γ in joint tissues.
- Synchronous activation of SIRT1 and PPAR-γ by MG is essential for repressing inflammatory responses in THP-1 monocytes.
Conclusions:
- MG initiates anti-inflammatory activity by binding to and activating PPAR-γ, subsequently promoting SIRT1 expression.
- This crosstalk mechanism involving PPAR-γ and SIRT1 is critical for MG's ability to reduce macrophage/monocyte inflammatory polarization in arthritis.
- MG's therapeutic potential in arthritis is mediated through the coordinated action of the SIRT1 and PPAR-γ signaling pathways.
