Effects of alpha-mangostin on the expression of anti-inflammatory genes in U937 cells

Abstract

Backgroundα-Mangostin (α-MG) is a main constituent of the fruit hull of the mangosteen. Previous studies have shown that α-MG has pharmacological activities such as antioxidant, antitumor, anti-inflammatory, antiallergic, antibacterial, antifungal and antiviral effects. This study aims to investigate the anti-inflammatory molecular action of α-MG on gene expression profiles.MethodsU937 and EL4 cells were treated with different concentrations of α-MG in the presence of 0.1 ng/mL lipopolysaccharide (LPS) for 4 h. The anti-inflammatory effects of α-MG were measured by the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-4 in cell culture media, which were determined with enzyme-linked immunosorbent assay kits. The gene expression profiles of all samples were analyzed with a whole human genome microarray, Illumina BeadChip WG-6 version 3, containing 48804 probes. The protein levels were determined by Western blotting analyses.Resultsα-MG decreased the LPS induction of the inflammatory cytokines TNF-α (P = 0.038) and IL-4 (P = 0.04). α-MG decreased the gene expressions in oncostatin M signaling via mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinases (P = 0.016), c-Jun N-terminal kinase (P = 0.01) , and p38 (P = 0.008). α-MG treatment of U937 cells reduced the phosphorylation of MAPK kinase 3 / MAPK kinase 6 (P = 0.0441), MAPK-activated protein kinase-2 (P = 0.0453), signal transducers and activators of transcription-1 (STAT1) (P = 0.0012), c-Fos (P = 0.04), c-Jun (P = 0.019) and Ets-like molecule 1 (Elk-1) (P = 0.038).ConclusionThis study demonstrates that α-MG attenuates LPS-mediated activation of MAPK, STAT1, c-Fos, c-Jun and EIK-1, inhibiting TNF-α and IL-4 production in U937 cells.

Analisis α-Mangostin dalam Minuman Herbal Kulit Buah Manggis (Garcinia mangostana L.) dengan Metode Kromatografi Lapis Tipis-Densitometri

“…Senyawa ini mempunyai berbagai aktifitas farmakologis seperti antioksidan, antitumor, antiinflamasi, antialergi, antibakteri dan antijamur [1,4,5,6,7].…”

The Pivotal Neuroinflammatory, Therapeutic and Neuroprotective Role of Alpha-Mangostin

“…1a). These signaling pathways in turn trigger a multiplicity of transcription factors such as NF-κB (p50/p65) and activator protein 1 (AP-1; c-Fos/c-Jun), which synchronize the stimulation of numerous genes encoding inflammatory mediators [115,118]. Nevertheless, the anti-inflammatory molecular consequence of α-MG is still a matter of debate.…”

“…Studies [115,116] have demonstrated that α-MG appreciably blocks NO, PGE2, TNF-α and iNOS generation in LPS-triggered RAW 264.7 cells (Fig.1b). PGE2, TNF-α and iNOS are cytokines implicated in inflammatory activities, such as amplified vascular penetrability, vascular dilation and neutrophil chemotaxis [115,117].…”

“…PGE2, TNF-α and iNOS are cytokines implicated in inflammatory activities, such as amplified vascular penetrability, vascular dilation and neutrophil chemotaxis [115,117]. Studies [115,118] have further proven that LPS activation of human monocytes triggers numerous intracellular signaling pathways such as IκB kinase (IKK), nuclear factor-κB (NF-κB) pathway as well as three MAPK pathways: extracellular signalregulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 (Fig. 1a).…”

Ekspresi COX-2 setelah pemberian ekstrak etanolik kulit manggis (Garcinia mangostana Linn) pada tikus wistar (COX-2 expression after mangosteen rind (Garcinia mangostana Linn) etanolic extract administration in wistar rats)

“…10 Gamma mangostin dari kulit buah manggis mampu menghambat ekspresi MAPK, NF-kB dan AP-1 dalam makrofag. 17 Hasil penelitian Liu et al 18 secara in vitro alfa mangostin kulit manggis terbukti mampu menurunkan induksi lipopolisakarida (LPS) terhadap sintesi sitokin pro inflamasi TNF-α dan IL-4 melalui penghambatan ekspresi gen oncostatin M pada jalur MAPK pada kultur sel U937.…”