A Novel Biological Role of α-Mangostin in Modulating Inflammatory Response Through the Activation of SIRT-1 Signaling Pathway

Abstract

Several studies have shown that xanthones obtained from Garcinia Mangostana (GM) have remarkable biological activities. α-mangostin (α-MG) is the main constituent of the fruit hull of the GM. Several findings have suggested that SIRT-1, a nuclear histone deacetylase, could influence cellular function by the inhibition of NF-kB signaling. ROS can inhibit SIRT-1 activity by initiating oxidative modifications on its cysteine residues, and suppression of SIRT-1 enhances the NF-κB signaling resulting in inflammatory responses. The goals of the present study were to evaluate the quantity of α-MG in the methanolic extract of GM (Vithagroup Spa) and to investigate the activity of this xanthone in U937 cell line and in human monocytes from responsive to inflammatory insult analyzing the possible changes on the activation of SIRT-1 protein via NF-Kb. Cells were treated with the methanolic extract of GM and/or LPS. The chromatographic separation of α-MG was performed by an HPLC analysis. EX 527, a specific SIRT-1 inhibitor, was used to determine if SIRT-1/NfkB signaling pathway might be involved in α-MG action on cells. Our results show that α-MG inhibits p65 acetylation and down-regulates the pro-inflammatory gene products as COX-2, iNOS via SIRT-1 activation. Cells treated with EX 527 showed an up-regulation of NFkB acetylation and an over expression of inducible enzymes and their product of catalysis (NO and PGE2). These results suggest that α-MG may be useful for the development of alternative pharmacological strategies aimed at reducing the inflammatory process. J. Cell. Physiol. 231: 2439-2451, 2016. © 2016 Wiley Periodicals, Inc.

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“…The overproduction of ROS inhibits SIRT-1 activity by initiating oxidative modifications on its cysteine residues, thereby enhancing NF-κB signaling resulting in inflammatory responses. As reported in a recent study, α-MG was observed to abrogate the acetylation of p65/NF-κB and NF-κB-regulated proinflammatory gene expressions, including COX-2 and iNOS, by activating SIRT-1 in the U937 cell line [67].…”

“…Mammary tumorigenesis↓, CYP1A1↓, CYP1A2↓, CYP1B1↓ Ex vivo mouse mammary organ culture assay [33] CYP19/aromatase activity↓ Microsomal [34] Protein expression and activity HO-1 ↑ Cerebellar granule neurons [35] Antioxidant aSMase activity↓ Enzyme derived-bovine brain [56] Making SOD, GPx, CAT recover to normal level Isoproterenol-induced myocardial infarction [38] Attenuation of inflammation NO release↓, PEG2 release↓, iNOS expression↓, COX-2 expression↓ LPS-stimulated RAW264.7 macrophage cells [61,62] Protein and mRNA expressions of COX-2↓, PEG2↓ Human breast cancer MDA-MB-231 cells [64] Direct interaction with COX-2 and iNOS Molecular modeling and docking study [65] SIRT-1↑, p65/NFκB acetylation↓, COX-2 expression↓, iNOS expression↓, NO production↓, PEG2 level↓ LPS-stimulated U937 cells [67] Induction of cell cycle arrest cyclinD1/CDK4 expression↓, p27KIP1 expression↑, cyclinE expression↓, phosphorylated Rb expression↓ direct interaction with CDK4…”

Biological Effect of Licochalcone C on the Regulation of PI3K/Akt/eNOS and NF-κB/iNOS/NO Signaling Pathways in H9c2 Cells in Response to LPS Stimulation

“…LPS, released from the surface of the cell membrane of Gram-negative bacteria, triggers an inflammatory response and causes severe sepsis. The cellular response to LPS includes the production of ROS and other mediators, such as NO and pro-inflammatory cytokines [30,31]. Therefore, we studied the possibility of LicoC in decreasing the cellular accumulation of ROS LPS-induced.…”

Development and in vivo evaluation of self‐microemulsion as delivery system for α‐mangostin

“…As the most important secondary metabolite in the plant, α‐mangostin (MG) is with the highest concentration among xanthones in mangosteen and draws intensive attentions worldwide for its significant clinical potentials these years [3]. Numerous documents have validated that it possesses substantial therapeutic potentials against cancers, infections, inflammations, Alzheimer's disease, obesity, and many other diseases [4–7].…”