In Vitro Anti-Inflammatory Effects of Quercetin 3-O-Methyl Ether and Other Constituents from Rhamnus Species

Abstract

The anti-inflammatory activities of the isolated flavonoids, quercetin 3-O-methyl ether (1), kaempferol (2), and quercetin (3), of Rhamnus nakaharai, and anthraquinone, frangulin B (4), of Rhamnus formosana, were assessed in vitro by determining their inhibitory effects on the chemical mediators released from mast cells, neutrophils, macrophages, and microglial cells. Compounds 1 - 3 strongly inhibited the release of β-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB). Compound 1 strongly inhibited superoxide anion formation in fMLP/CB or phorbol 12-myristate 13-acetate (PMA)-stimulated rat neutrophils. Compound 1 exhibited potent inhibitory effect on tumor-necrosis factor-α ( TNF-α) formation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells while 1 and 4 showed potent inhibitory effects on TNF-α formation in LPS/IFN-γ (interferon-γ)-stimulated murine microglial cell lines N9.

References

• 1 Middleton E, Kandaswami C. Effects of flavonoids on immune and inflammatory cell functions.  Biochem. Pharmacol.. 1992;  43 1167-79
• 2 Ding A H, Nathan C F, Stuehr D J. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages.  J. Immunol.. 1988;  141 2407-12
• 3 Mallat M, Chamak B. Brain Macrophages: Neurotoxic or neurotrophic effector.  Cell. Leukoc J. Biol.. 1994;  56 416-22
• 4 Gehrmann J, Matsumoto Y, Kreutzberg G W. Microglia: Intrinsic immuneffector cell of the brain.  Brain Res. Rev.. 1995;  20 269-87
• 5 Wei B L, Lin C N, Won S J. Naphthalene and cytotoxic principles of Formosan Rhamnus plants.  J. Nat. Prod.. 1992;  55 967-9
• 6 Lin C N, Lu C M, Lin H C, Ko F N, Teng C M. Novel antiplatelet naphthalene from Rhamnus nakaharai .  J. Nat. Prod.. 1995;  58 1934-40
• 7 Lin C N, Chung M I, Lu C M. Anthraquinones from Phamnus formosana .  Phytochemistry. 1990;  29 3903-5
• 8 Alexandrakis M, Singh L, Boucher W, Letourneau R, Theofilopoulos P, Theoharides T C. Differential effect of flavonoids on inhibition of secretion and accumulation of secretory granules in rat basophilic leukemia cells. Int.  J. Immunopharmacol.. 1999;  21 379-90
• 9 Tordera M, Ferrandiz M L, Alcaraz M J. Influence of anti-inflammatory flavonoids on degranulation and arachidonic acid release in rat neutrophils.  Z. Naturforsch C.. 1994;  49 235-40
• 10 Segal A W, Abo A. The biochemical basis of the NADPH oxidase of phagocytes.  Trends Biochem. Sci.. 1993;  18 43-7
• 11 Takemura O S, Banno Y, Nozawa Y. Inhibition of N-formylmethionyl-leucyl-phenylalanine-stimulated tyrosine phosphorylation and phospholipase D activation by quercetin in rabbit neutrophils.  Biochem. Pharmacol.. 1997;  53 1503-10
• 12 Meda L, Cassatella M A, Szendrei G I, Otvos J r. L, Baron P, Villelba M, Ferrari D, Ross F. Activation of microglial cells by β-amyloid protein and interferon-γ.  Nature. 1995;  374 647-50
• 13 Beuther B, Cerami A. Tumor necrosis factor, cachexia, shock, and inflammation: a common mediator.  Anm. Rev. Biochem.. 1988;  57 505-18
• 14 Wadsworth T L, Koop D R. Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 Macrophages.  Biochem. Pharmacol.. 1999;  57 941-91
• 15 Wang J P, Raung S L, Lin C N, Teng C M. Inhibitory effect of norathyriol, a Xanthone from Tripterospermun lanceolatum, on Cutameous plasma extravasation.  Eur. J. Pharmacol.. 1994;  251 35-42
• 16 Boyum A. Isolation of mononuclear cells and granulocytes from blood.  Scand J. Clin. Invest.. 1968;  97 (Suppl.) 77-89
• 17 Smith R J, Iden S S. Phorbol myristate acetate-induced release of granule enzymes from human neutrophils: Inhibition by the calcium antagonist, 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate hydrochloride.  Biochem. Biophys. Res. Commun.. 1979;  91 263-71
• 18 Market M, Andrews P C, Babior B M. Measurement of O₂ ^--production by human neutrophils. The preparation and assay of NADPH oxidase-containing particles from human neutrophils.  Methods Enzymol.. 1984;  105 358-65
• 19 Corradin S B, Mauel J, Donini S D, Quattrocchi P, Ricciardi-Casragnoli P. Inducible nitric oxide synthase activity of cloned murine microglial cells.  Glia. 1993;  7 255-62
• 20 Minghetti L, Nicolini A, Polazzi E, Creminon C, Maclouf J, Levi G. Inducible nitric oxide synthase expression in activated rat microglial cultures is downregulated by exogenous prostaglandin E₂ and by cyclooxygenase inhibitor.  Glia.. 1997;  19 152-60