A citrus flavonoid, nobiletin, suppresses production and gene expression of matrix metalloproteinase 9/gelatinase B in rabbit synovial fibroblasts.
Journal of Rheumatoly. 2000 January;27(1):20-5
This study investigated the protective effect of citrus flavonoids on connective tissue. More specifically the researchers investigated their influence on the production of matrix metalloproteinases and prostaglandin E2 in cultured rabbit fibroblasts. They found that all flavonoids isolated from Citrus depressa Rutaceae suppressed the interleukin-1 induced production of promatrix metalloproteinases -9 and progelatinase B. Nobiletin was the most active anti-inflammatory flavonoid and may help to inhibit prostaglandin E2 production, matrix degradation and pannus tissue formation in osteoarthritis and rheumatoid arthritis.
Anti-inflammatory property of the urinary metabolites of nobiletin in mouse.
Bioorganic & Medicinal Chemistry Letters .2007 September 15;17(18):5177-81
The citrus flavonoid nobiletin contains 5 methoxyl groups. Nobiletin has many claimed benefits including anti-inflammatory and anti-carcinogenic activities. Li et al found that the metabolites of nobiletin, which contained 1 or 2 fewer methoxyl groups showed even higher anti-inflammatory activity than nobiletin.
Nobiletin from citrus fruit peel inhibits the DNA-binding activity of NF-kappaB and ROS production in LPS-activated RAW 264.7 cells.
Journal of Ethnopharmacology. 2007 August15;113(1):149-55
This study tested the effect of a post-treatment with nobiletin on mouse leukaemic monocyte macrophages after activation with lipopolysaccharides. The nobiletin was purified form the peel of mandarins (Citrus sunki Hort. ex Tanaka). The researched found no effect of nobiletin on phosphorylation of inhibitory kappaB-alpha or nuclear translocation of NF-kappaB. However, nobiletin interrupted the DNA-binding activity of activated NF-kappaB. They also found that nobiletin significantly inhibited the production of free radicals in the macrophages after activation with lipopolysaccharides. They concluded that nobiletin may exert its anti-inflammatory effect by blocking the NF-kappaB DNA-binding activity and the suppression of the formation of free radicals.
Antagonistic effects of nobiletin, a polymethoxyflavonoid, on eosinophilic airway inflammation of asthmatic rats and relevant mechanisms.
Life Science. 2006 May 1;78(23):2689-96
Eosinophils are white blood cells of the immune system that are responsible for combating infection and parasites. Eosinophils are also effector cells in allergic responses and asthma pathogenesis and are associated with disease severity. The aim of this study was to investigate the effect of the citrus flavonoid nobiletin the airway inflammation of asthmatic rats and to establish possible mechanisms. The rats were sensitized by injection of ovalbumin and the resulting inflammation was measured by hematoxylin and eosin staining. The number of eosinophils in blood and broncho-alveolar lavage fluid were determined as well as the level of eotaxin, a cytokine that selectively recruits eosinophils by inducing their chemotaxis. The researchers found that pre-treatment of the asthmatic rats with nobiletin reduced the airway inflammation, reduced the numbers of eosinophils and significantly lowered the eotaxin levls in blood and broncho-alveolar lavage fluid. An in-vitro test with cultured eosinophils showed that their apoptosis was significantly increased after treatment with nobiletin. Nobiletin enhanced the expression of Fas mRNA.. The study concluded that nobiletin could be used to inhibit the eosinophilic airway inflammation. Nobiletin worked by lowering the levels of eotaxin, reducing infiltration by eosinophils and inducing apoptosis of eosinophils.
Prevention of UVB-induced photoinflammation and photoaging by a polymethoxy flavonoid, nobiletin, in human keratinocytes in vivo and in vitro.
Biochemical Pharmacology. 2004 August 1;68(3):433-9.
Skin exposure to ultraviolet B can result in sunburn and edema (swelling caused by increase in interstitial fluid in the skin). These inflammatory reactions are mediated by prostaglandin E2. In the first experiment the researchers tested the effect of nobiletin on cultured skin cells, exposed to ultraviolet B radiation. Treatment of skin cells with ultraviolet B radiation results in increased expression of the cyclooxygenases-2 and increased level of prostaglandin E2. They found that nobiletin reversed this increase in cyclooxygenases-2 and inhibited the release of arachidonic acid. The second experiment was carried out on hairless mice which were also exposed to ultraviolet B radiation. Normally, this treatment results in water loss and hyperplasia of the epidermis, but the treatment with nobiletin inhibited these reactions. They concluded that nobiletin may be useful as a novel sunscreen reagent.
Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages.
Biochemical Pharmacology. 2003 June 15;65(12):2065-71
Department of Biochemistry and Molecular Biology, School of Pharmacy, Tokyo University of Pharmacy and Life Science (Japan).
The aim of this study was to determine the effect of nobiletin on the production of cyclooxygenases, prostaglandin E2 and proinflammatory cytokines in human synovial fibroblasts and the mouse macrophages. Nobiletin suppressed the interleukin-1-induced production of prostaglandin E2 in human synovial cells and reduced the production of cyclooxygenases-1. In the cultured mouse macrophages, nobiletin also reduced the lipopolysaccharide-induced production of prostaglandin E2 and the gene expression of proinflammatory cytokines. The production of TIMP-1, a tissue inhibitor of matrix metalloproteinases, was increased. The anti-inflammatory actions of nobiletin are comparable to those of other anti-inflammatory steroids. They concluded that nobiletin is a potential immunomodulatory and anti-inflammatory drug.
In vitro absorption and metabolism of nobiletin, a chemopreventive polymethoxyflavonoid in citrus fruits.
Bioscience Biotechnology and Biochemistry. 2001 January;65(1):194-7
The aim of this study was to compare the absorption and metabolism of nobiletin, a polymethoxylated flavonoid, with that of luteolin, a polyhydroxylated flavonoid. Research on nobiletin is important as this phytochemical, which is found in citrus fruits, has a promising anti-inflammatory and anti-tumour activities. The researchers found that nobiletin, but not luteolin, preferentially accumulated in a cultured layer of Caco-2 cells, which is used as an in vitro assay to predict the absorption rate and is a model for small intestinal epithelial cells. Treatment of nobiletin with a rat liver homogenate led to the formation of 3'-demethyl-nobiletin. They concluded that polymethoxylated flavonoids have unique absorption and metabolism properties in-vitro.
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