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

U937 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.α-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).This 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.The mangosteen fruit has been used in Chinese and Ayurvedic medicine [1]. Extracts of mangosteen have antioxidant, antitumor, anti-inflammatory, antiallergic, antibacterial, antifungal and antiviral effects [1-3]. α-Mangostin (α-MG), which was first isolated from the mangosteen in 1855, is a competitive antagonist of the histamine H1 receptor and possesses many biological properties, such as anti-inflammatory, anti-oxidative damage and antioxidant activities [4-6]. Previous studies have shown that α-MG significantly inhibits nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α and inducible NOS (iNOS) pro