Anti-Inflammatory Effect of 1,3,5,7-Tetrahydroxy-8-isoprenylxanthone Isolated from Twigs of Garcinia esculenta on Stimulated Macrophage

• Published in: Mediators of Inflammation 2015-01, Vol.2015 (2015), p.440-450-141
• Main Authors: Xu, Hong-Xi, Murad, Ferid, Xu, Jin-wen, Wu, Rong, Lao, Yuanzhi, Zhang, Hong, Zhang, Dan-Dan, Bian, Ka
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Cell Survival; Chinese medicine; Cyclooxygenase 2 - metabolism; Dinoprostone - metabolism; Garcinia - chemistry; Health aspects; Inflammation; Interleukin-6 - metabolism; Kinases; Lipopolysaccharides - chemistry; Macrophages; Macrophages - drug effects; Mice; NF-kappa B - metabolism; Nitric oxide; Nitric Oxide - chemistry; Nitric Oxide Synthase Type II - metabolism; Plant Extracts - chemistry; RAW 264.7 Cells; Salicylates; Signal Transduction; Tumor necrosis factor-TNF; Xanthones - isolation & purification; Xanthones - pharmacology; Xanthones - therapeutic use
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2015/350564

Garcinia Linn. plants having rich natural xanthones and benzophenones with anti-inflammatory activity attracted a great deal of attention to discover and develop them as potential drug candidates. Through screening targeting nitric oxide accumulation in stimulated macrophage, we found that 1,3,5,7-tetrahydroxy-8-isoprenylxanthone (TIE) had potential anti-inflammatory effect. To understand how TIE elicits its anti-inflammatory activity, we uncovered that it significantly inhibits the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS/IFNγ-stimulated RAW264.7 cells. In further study, we showed that TIE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), two key molecules responsible for the production of NO and PGE2 during inflammation progress. Additionally, TIE also suppressed the expression of inflammatory cytokines IL-6, IL-12, and TNF-α. TIE-led suppression in iNOS, COX-2, and cytokines production were probably the consequence of TIE’s capability to block ERK and p38MAPK signaling pathway. Moreover, TIE blocked activation of nuclear factor-kappa B (NF-κB) as well as NF-κB regulation of miR155 expression. Our study suggests that TIE may represent as a potential therapeutic agent for the treatment of inflammatory diseases.