2-3-6-8-tetrahydroxy-1-(3-methylbut-2-enyl)-5-(2-methylbut-3-en-2-yl)-9h-xanthen-9-one and Inflammation

SIRT1, a member of the sirtuin family, belongs to the NAD⁺-dependent class III histone deacetylase. SIRT1 can regulate gene expression by catalyzing non-histone and histone lysine residues deacetylation. SIRT1 also plays important roles in glucose and lipid metabolism, cell aging, tumorigenesis and inflammation. Recent studies indicate that SIRT1 can inhibit the inflammatory responses via regulating several inflammatory signaling pathways. It is closely related to the occurrence and development of sepsis and other inflammatory diseases. Research has been done on relevant signaling pathways of SIRT1 as well as its target genes during inflammation. SIRT1 is a hot spot in uncontrolled inflammatory response research. This article focuses on the role of SIRT1 in inflammation, especially its targets and involved signaling pathways in sepsis, and tries to provide more convincing evidence for the clinical treatment of sepsis and other inflammatory diseases.

Topics: Animals; Glucosides; Humans; Inflammation; Phenols; Resveratrol; Sepsis; Signal Transduction; Sirtuin 1; Xanthones

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.

Topics: Animals; Inflammation; Lipopolysaccharides; MAP Kinase Signaling System; Mice; Microglia; Moraceae; NF-kappa B p50 Subunit; p38 Mitogen-Activated Protein Kinases; Transcription Factor RelA; Xanthones