Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages

Lin, Na; Sato, Takashi; Takayama, Yoshiaki; Mimaki, Yoshihiro; Sashida, Yutaka; Yano, Masamichi; Ito, Akira

doi:10.1016/s0006-2952(03)00203-x

Cited by 271 publications

(197 citation statements)

References 23 publications

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“…MMPs are major components of the enzyme cascade responsible for degradation of the extracelullar matrix in many organs including bone, brain and liver 7,19,20 . The activities and expressions of MMPs are tightly regulated by various factors and aberrant regulations of MMPs are contributed to the pathogenesis of diverse diseases.…”

Section: Discussionmentioning

confidence: 99%

“…MMPs expression can be induced in various pathological conditions including inflammation. Many studies reported the increased MMPs expression by the proinflammatory cytokines such as IL-1β and TNF-α in many cell types such as chondrocytes, synoviocytes, macrophages and astrocytes 7,16,20 . In addition, IL-1 has been reported to induce MMPs expression in osteoblastic cell lines and primary cultured osteoblasts 21 .…”

Section: Discussionmentioning

confidence: 99%

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Luteolin downregulates IL-1β-induced MMP-9 and -13 expressions in osteoblasts via inhibition of ERK signalling pathway

Yang

Liu

Ahn

et al. 2011

Journal of Enzyme Inhibition and Medicinal Chemistry

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Luteolin downregulates IL-1β-induced MMP-9 and -13 expressions in osteoblasts via inhibition of ERK signalling pathway

Yang

Liu

Ahn

et al. 2011

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…On the other hand, there are a number of reports concerning a variety of biological effects of tangeretin and nobiletin, especially nobiletin, in addition to the concentrations of polymethoxy flavones in various species of citrus (10,11). For instances, direct and indirect evidences have been provided for anti-cancer effects (12)(13)(14)(15)(16)(17)(18)(19)(20), anti-inflammatory effects (21)(22)(23)(24), inhibition of NO production (25,26), enhancement of differentiation and lipolysis of adipocytes (27), prevention of cartilage destruction (28), improvement of memory impairment (29) and neurodegradation (30). However, no liver injury-suppressive effect of tangeretin and nobiletin has been reported yet.…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effects of Flavonoids from Shekwasha (Citrus depressa) against D-Galactosamine-Induced Liver Injury in Rats

Akachi

Shiina

Ohishi

et al. 2010

J Nutr Sci Vitaminol

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SummaryWe attempted to isolate the constituent(s) responsible for the suppressive effect of the juice of shekwasha, a citrus produced in Okinawa Prefecture, on D -galactosamine (GalN)-induced liver injury in rats. Liver injury-suppressive activity, as assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, was found only in the fraction that was extracted with n -hexane when three fractions were added to the diet and fed to rats. Of five compounds isolated from the n -hexane-soluble fraction by silica gel column chromatography, three compounds had liver injury-suppressive effects when five compounds were singly force-fed to rats at a level of 300 mg/kg body wt 4 h before the injection with GalN. The structures of the three active compounds were determined as 3 ′ ,4 ′ ,5,6,7,8-hexamethoxyflavanone (citromitin), 4 ′ ,5,6,7,8-pentamethoxyflavone (tangeretin) and 3 ′ ,4 ′ ,5,6,7,8-hexamethoxyflavone (nobiletin), which are known flavonoids mainly existing in citrus. Nobiletin, the most important compound in the n -hexane-soluble fraction, also had suppressive effects on liver injuries induced by carbon tetrachloride, acetaminophen and GalN/lipopolysaccharide (LPS) in addition to liver injury induced GalN. Nobiletin suppressed GalN/LPS-induced increases in plasma tumor necrosis factor (TNF)-␣ and nitric oxide (NO) concentrations and hepatic mRNA levels for inducible NO synthase and DNA fragmentation. These results suggest that nobiletin suppressed GalN/LPS-induced liver injury at least by suppressing the production of both TNF-␣ and NO. The results obtained here indicate that the hepatoprotective effect of shekwasha juice is mainly ascribed to several polymethoxy flavonoids included in the juice. Key Words D -galactosamine, liver injury, shekwasha, Citrus depressa , flavonoids Fruits and vegetables are important as sources of several nutrients such as vitamins, minerals and dietary fibers. Fruits and vegetables also contain a variety of constituents, which are characteristic of the species of plant. It is widely recognized that relatively high intakes of fruits and vegetables are desirable for prevention of diseases and maintenance of healthy conditions ( 1 ). Previously we reported that several kinds of fruit had suppressive effects on D -galactosamine (GalN)-induced liver injury in rats when various kinds of lyophilized fruit were added to the diet ( 2 ). Furthermore, recently we found that some fruit juices, e.g., camu-camu and shekwasha, also had suppressive effects on GalNinduced liver injury in rats, and we identified the active compound (unpublished data). These findings indicate that certain fruits (and possibly vegetables) have a hepatoprotective effect in addition to nutritional effects.Since the liver is the central organ of many types of metabolism, the hepatoprotective effect of foods is worthwhile to investigate in detail, not only from the viewpoint of food science but also from the viewpoint of nutrition.In the present study, we attempted to isolate the constituent(s) res...

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“…Due to the proven ability of flavonoids to inhibit specific enzymes, to simulate some hormone secretions and neurotransmitters and to scavenge free radicals, pure flavonoids are used to treat many common diseases [90,94,99]. Polymethoxylated flavones are known for their anticancer [100], anti-inflammatory [101], and neuro-protective [102] properties. Flavonoids from Theobroma cacao caused dose-dependent reduction of interleukin (IL)-2Ra (CD25) expression in activated lymphoid cell line, which suggests the potentials of the use flavonoids in counteracting immune system hyperactivity such as chronic autoimmune inflammatory disease [103].…”

Section: Flavonoidsmentioning

confidence: 99%

Medicinal Potentials and Toxicity Concerns of Bioactive Principles

CO¹

2015

Med Aromat Plants

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Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages

Cited by 271 publications

References 23 publications

Luteolin downregulates IL-1β-induced MMP-9 and -13 expressions in osteoblasts via inhibition of ERK signalling pathway

Luteolin downregulates IL-1β-induced MMP-9 and -13 expressions in osteoblasts via inhibition of ERK signalling pathway

Hepatoprotective Effects of Flavonoids from Shekwasha (Citrus depressa) against D-Galactosamine-Induced Liver Injury in Rats

Medicinal Potentials and Toxicity Concerns of Bioactive Principles

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