A Novel Biological Role of α-Mangostin via TAK1-NF-κB Pathway against Inflammatory

Abstract

The oxysterone α-mangostin is isolated from mangosteen husks and is widely used in the treatment of abdominal pain, diarrhea, and dysentery. In this study, we established a lipopolysaccharide (LPS)-induced inflammatory model of rat intestinal epithelial cells (IEC-6 cells), at the same time we used differently concentration α-mangostin to detect its anti-inflammatory activity. We applied doses of α-mangostin (2.5, 5, and 10 μM) and detected apoptosis by flow cytometry, and the Griess reagent and the enzyme-linked immunosorbent assay (ELISA) method detected inflammatory factors such as nitric oxide (NO), prostaglandin (PG) E2, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. We also used quantitative real-time PCR (Q-PCR) to examine inflammatory factors and western blotting to examine the activation of transforming growth factor-activated kinase (TAK)-1-nuclear factor (NF)-κB signaling pathway-related proteins. Finally, we used laser confocal microscopy to detect the effect of the 10 μM α-mangostin on the nuclear import of NF-κB-p65. The results showed that α-mangostin treatment significantly reduced the apoptosis of LPS-stimulated IEC-6 cells, the production of inflammatory factors, the activation of TAK1-NF-κB signaling pathway-related proteins, and the entry of p65 into the nucleus. In conclusion, α-mangostin exerts its anti-inflammatory effects by inhibiting the activation of TAK1-NF-κB and it may be a potential choice for the treatment of inflammation diseases.

Keywords: LPS; NF-κB; TAK1; inflammatory; α-mangostin.