title: Anti-Inflammatory Effect of 1,3,5,7-Tetrahydroxy-8-isoprenylxanthone Isolated from Twigs of Garcinia esculenta on Stimulated Macrophage.
abstract: 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.
authors.affiliation: Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Cailun Road 1200, Shanghai 201203, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Cailun Road 1200, Shanghai 201203, China ; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Cailun Road 1200, Shanghai 201203, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Cailun Road 1200, Shanghai 201203, China ; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Cailun Road 1200, Shanghai 201203, China.
authors.forename: Yuan-zhi
authors.initials: YZ
authors.lastname: Lao
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Cailun Road 1200, Shanghai 201203, China ; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Cailun Road 1200, Shanghai 201203, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.affiliation: Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Cailun Road 1200, Shanghai 201203, China.
authors.forename: Jin-wen
authors.initials: JW
authors.lastname: Xu
authors.affiliation: Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Cailun Road 1200, Shanghai 201203, China ; Department of Biochemistry and Molecular Medicine, George Washington University, I Street, Washington, DC 20037, USA.
authors.forename: Ferid
authors.initials: F
authors.lastname: Murad
authors.affiliation: Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Cailun Road 1200, Shanghai 201203, China ; Department of Biochemistry and Molecular Medicine, George Washington University, I Street, Washington, DC 20037, USA.
authors.forename: Ka
authors.initials: K
authors.lastname: Bian
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Cailun Road 1200, Shanghai 201203, China ; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Cailun Road 1200, Shanghai 201203, China.
authors.forename: Hong-Xi
authors.initials: HX
authors.lastname: Xu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D029760:Garcinia / Q000737:chemistry*; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction; D044004:Xanthones / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C000609902:1,3,5,7-tetrahydroxy-8-isoprenylxanthone; D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D044004:Xanthones; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone