A Prenylated Xanthone, Cudratricusxanthone A, Isolated from Cudrania tricuspidata Inhibits Lipopolysaccharide-Induced Neuroinflammation through Inhibition of NF-κB and p38 MAPK Pathways in BV2 Microglia.

Abstract

Cudrania tricuspidata Bureau (Moraceae) is an important source of traditional Korean and Chinese medicines used to treat neuritis and inflammation. Cudratricusxanthone A (1), a prenylated xanthone, isolated from C. tricuspidata, has a variety of biological and therapeutic activities. The goal of this study was to examine the effects of compound 1 on neuroinflammation and characterize its mechanism of action in lipopolysaccharide (LPS)-stimulated BV2 microglia. Cudratricusxanthone A (1) suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 enzymes and decreased the production of iNOS-derived nitric oxide and COX-2-derived prostaglandin E2 in LPS-stimulated mouse BV2 microglia. The compound also decreased tumor necrosis factor-α, interleukin (IL)-1β, and IL-12 production; inhibited the phosphorylation and degradation of IκB-α; and blocked the nuclear translocation of p50 and p65 in mouse BV2 microglia induced by LPS. Cudratricusxanthone A (1) had inhibitory effects on nuclear factor kappa B DNA-binding activity. Additionally, it inhibited the p38 mitogen-activated protein kinase signaling pathway. Our data suggests that cudratricusxanthone A (1) may be a useful therapeutic agent in the treatment of neurodegenerative diseases caused by neuroinflammation.

• Authors: Chi-Su Yoon, Dong-Cheol Kim, Tran Hong Quang, Jungwon Seo, Dae Gill Kang, Ho Sub Lee, Hyuncheol Oh, Youn-Chul Kim
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 21 Issue 9 (Sep 16 2016) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 27649130 (Publication Type: Journal Article)

Chemical References

• Lipopolysaccharides
• NF-kappa B p50 Subunit
• Rela protein, mouse
• Transcription Factor RelA
• Xanthones
• cudratricusxanthone A
• Nfkb1 protein, mouse
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Inflammation (chemically induced, drug therapy, metabolism, pathology)
• Lipopolysaccharides (toxicity)
• MAP Kinase Signaling System (drug effects)
• Mice
• Microglia (metabolism, pathology)
• Moraceae (chemistry)
• NF-kappa B p50 Subunit (metabolism)
• Transcription Factor RelA (metabolism)
• Xanthones (chemistry, isolation & purification, pharmacology)
• p38 Mitogen-Activated Protein Kinases (metabolism)