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.

<p>JAZF1 Suppresses Papillary Thyroid Carcinoma Cell Proliferation and Facilitates Apoptosis via Regulating TAK1/NF-κB Pathways</p>

“…TAK1 is a pivotal kinase upstream of the NF-κB signalling pathway 24. Zou et al revealed that α-mangostin-mediated inflammation inhibition may through the inhibition of TAK1-NF-κB pathways activation 49. Wang et al found that CXC195 exerts antiproliferation of human hepatocellular cancer cells via regulating the TAK1-mediated NF-κB pathway 50.…”

Existence of α‐mangostin conformers and effects of aprotic and protic solvents on their equilibria, UV–Vis spectra, and chemical descriptors: Density functional theory and time‐dependent density functional theory study

“…α-Mangostin has been extracted from the rind of mangosteen fruit using 1,2-propanediol-betaine, [2] ethyl acetate, [3] and supercritical CO 2 [4] as a green solvent, and from the pericarp with water, [5] and water at 65 C [6] and purification through solid phase extraction. [7] α-Mangostin has been reported to have anti-acne activity, [8] inhibit mutant IDH1, [9] prevent and treat hepatocellular carcinoma, [10] and exhibit antiinflammatory, [11][12][13][14] antibacterial, [15,16] antitumor, [17,18] and antimetastatic properties in many cancer cell types. [19] The biological activities and pharmacological properties of α-mangostin as an antineoplastic agent, antioxidant, antiproliferation agent for the induction of apoptosis, [20] and as a lysine-specific demethylase 1 (LSD1) inhibitor against tumor metastasis [21] have been reviewed.…”

“…The antioxidant and neuroprotective effects of α-mangostin on 6-hydroxydopamine-induced toxicity in SH-SY5Y cells as an in vitro model for Parkinson's disease have been demonstrated. [22] Moreover, α-mangostin has been found to inhibit the production of both dengue virus and cytokines/chemokines, [23] act as antiviral and anti-inflammatory agent in the treatment of dengue fever, [24] have a biological role via the TAK1-NF-κB pathway against inflammation, [25] induce the necrotic death of BT474 breast cancer cells through autophagy and inflammation, [26] and exhibit inhibitory effects on cholangiocarcinoma cells and allografts. [27] The α-mangostin showed apoptotic effect on human breast cancer cells via inhibiting activity of fatty acid synthase (FAS), [28] abrogates anoikis resistance in human hepatocellular carcinoma cells [19] and migration and invasion of A549 lung cancer cells.…”

Using high-throughput sequencing to explore the anti-inflammatory effects of α-mangostin

“…IEC-6 cells are small intestinal epithelial cells that are important components of the mechanical barrier afforded by the small intestine, and their integrity plays an important role in intestinal immunity 4,5 . Because IEC-6 cells express Toll-like receptors (TLRs), including TLR2 and TLR4, they recognize LPS 6,7 , a component of the outer membranes of Gram-negative bacteria, and have been widely used for in vivo and in vitro studies of the inflammatory response 8–10 . Studies have shown that LPS increases the expression of inflammatory factors and chemokines, and causes physiological and morphological changes to tissues 11–14 .…”

“…α-MG, the main component of mangosteen peel, is widely used for its anti-inflammatory and antioxidant properties 29,30 . It has been reported that α-MG exerts its anti-inflammatory effects by inhibiting the expression of tumor necrosis factor α (TNF-α), cyclooxygenase 2 (COX2), and prostaglandin-endoperoxide synthase 2 (PGE2), and inhibits the activation of the MAPK and NF-κB signaling pathways 6,31,32 . It has also been reported that α-MG exerts an antioxidant effect by inhibiting the production of ROS 26,33 .…”