Anti-inflammatory property of the urinary metabolites of nobiletin in mouse

Li, Shiming; Sang, Shengmin; Pan, Min‐Hsiung; Lai, Ching-Shu; Lo, Chih-Yu; Yang, Chung S.; Ho, Chi‐Tang

doi:10.1016/j.bmcl.2007.06.096

Cited by 136 publications

(106 citation statements)

References 20 publications

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“…Further, in the blood serum, maximum levels of glucuronidated metabolites occurred later than nobiletin and tangeretin and occurred at higher concentrations than aglycone metabolites (Manthey et al, 2011). It is also confirmed in previous trials that overall expression of biological actions of nobiletin and tangeretin in animals is due to the biological actions of aglycone metabolites (Eguchi et al, 2007;Li et al, 2007;Lai et al, 2008;Xiao et al, 2009). …”

Section: Bioavailability Of a Nutrient Is Simply The Quantity Or Fracmentioning

confidence: 52%

Bioavailability of Citrus Polymethoxylated Flavones and Their Biological Role in Metabolic Syndrome and Hyperlipidemia

Evans¹,

Sharma²,

Guthrie³

2012

Readings in Advanced Pharmacokinetics - Theory, Methods and Applications

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Section: Bioavailability Of a Nutrient Is Simply The Quantity Or Fracmentioning

confidence: 52%

Bioavailability of Citrus Polymethoxylated Flavones and Their Biological Role in Metabolic Syndrome and Hyperlipidemia

Evans¹,

Sharma²,

Guthrie³

2012

Readings in Advanced Pharmacokinetics - Theory, Methods and Applications

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“…The results demonstrated that inotilone has an inhibitory effect on LPS-induced NO and PGE 2 production in RAW 264.7 while methylinotilone showed no effect on both of these inflammatory mediators. Several structure-activity relationships studies have indicated that flavonoids with a 4 0 -OH substitution in the B-ring show better anti-inflammatory effect than 3 0 -OH-4 0 -methoxy substitution [35,36]. We reported previously that 3 0 ,4 0 -didemethylnobiletin is a more potent anti-inflammatory and anti-tumor agent compared with its parent compound, nobiletin [37].…”

Section: Discussionmentioning

confidence: 96%

Differential inhibitory effects of inotilone on inflammatory mediators, inducible nitric oxide synthase and cyclooxygenase‐2, in LPS‐stimulated murine macrophage

Kuo

Lai

Wang

et al. 2009

Molecular Nutrition Food Res

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The inhibitory effects of inotilone and methylinotilone on the induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with LPS were investigated. The results show that both hydroxyl groups on the benzene ring of the inotilone molecule are required for better anti-inflammatory effect. Western blotting and RT-PCR analyses demonstrated that inotilone blocked protein and mRNA expression of iNOS but not COX-2. Instead, inotilone inhibited prostaglandin E(2) production through decreasing the enzyme activity of COX-2. The repression of iNOS but not COX-2 expression may come from the differential effect of inotilone on nuclear factor-kappaB (NFkappaB) and CCAAT/enhancer-binding protein beta Treatment with inotilone resulted in the reduction of LPS-induced nuclear translocation of NFkappaB subunit and the NFkappaB-dependent transcriptional activity by blocking phosphorylation of inhibitor kappaB(IkappaB)alpha and p65 and subsequent degradation of inhibitor kappaBalpha. Inotilone also inhibited LPS-induced activation of PI3K/Akt and extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase. Our results suggest that inotilone may have potential to be developed into an effective anti-inflammatory agent.

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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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Anti-inflammatory property of the urinary metabolites of nobiletin in mouse

Cited by 136 publications

References 20 publications

Bioavailability of Citrus Polymethoxylated Flavones and Their Biological Role in Metabolic Syndrome and Hyperlipidemia

Bioavailability of Citrus Polymethoxylated Flavones and Their Biological Role in Metabolic Syndrome and Hyperlipidemia

Differential inhibitory effects of inotilone on inflammatory mediators, inducible nitric oxide synthase and cyclooxygenase‐2, in LPS‐stimulated murine macrophage

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

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