Identification of novel bioactive metabolites of 5-demethylnobiletin in mice

Zheng, Jinkai; Song, Mingyue; Dong, Ping; Qiu, Peiju; Guo, Shan-Shan; Zhong, Zhimei; Li, Shiming; Ho, Chi Tang; Xiao, Hang

doi:10.1002/mnfr.201300211

Cited by 67 publications

(78 citation statements)

References 32 publications

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“…The same results were observed in O-methylated flavonoids, which showed weaker antioxidation than their respective aglycones [60]. As an example, 5,3-didemethylnobiletin showed much stronger inhibitory effect on human colon cancer cell growth than 5-demethylnobiletin by cell viability assay [61]. These correlations between the flavonoid structure and their free radical scavenging activity need to be further investigated for better understanding and clinical application.…”

Section: Anticarcinogenic Propertiesmentioning

confidence: 61%

Anticancer Activities of Citrus Peel Polymethoxyflavones Related to Angiogenesis and Others

Wang

Fang

et al. 2014

BioMed Research International

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103

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Citrus is a kind of common fruit and contains multiple beneficial nutrients for human beings. Flavonoids, as a class of plant secondary metabolites, exist in citrus fruits abundantly. Due to their broad range of pharmacological properties, citrus flavonoids have gained increased attention. Accumulative in vitro and in vivo studies indicate protective effects of polymethoxyflavones (PMFs) against the occurrence of cancer. PMFs inhibit carcinogenesis by mechanisms like blocking the metastasis cascade, inhibition of cancer cell mobility in circulatory systems, proapoptosis, and antiangiogenesis. This review systematically summarized anticarcinogenic effect of citrus flavonoids in cancer therapy, together with the underlying important molecular mechanisms, in purpose of further exploring more effective use of citrus peel flavonoids.

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Section: Anticarcinogenic Propertiesmentioning

confidence: 61%

Anticancer Activities of Citrus Peel Polymethoxyflavones Related to Angiogenesis and Others

Wang

Fang

et al. 2014

BioMed Research International

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103

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“…This may be associated with the metabolism of 5-HPMF as previously demonstrated in our laboratory. 30 The presence of oleic acid in the mixed micelles appeared to have a transport-enhancing effect: there was an increase in cellular accumulation relative to the control (Fig. 3C) and an increase in the rate and extent of basolateral 5-HPMF (Fig.…”

Section: Discussionmentioning

confidence: 91%

Enhanced lymphatic transport of bioactive lipids: cell culture study of polymethoxyflavone incorporation into chylomicrons

et al. 2013

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Polymethoxyflavones (PMFs) are bioactive flavonoids found in citrus fruits that have been shown to have potential health promoting properties. However, their application as nutraceuticals in functional foods and beverages is currently limited due to their low water solubility and high melting point. The oral bioavailability of lipophilic compounds can be enhanced by promoting their intestinal lymphatic transport through co-administration with digestible lipids. We investigated the effects of chylomicron-mediated intestinal lymphatic transport on the bioavailability of 5-hydroxy-6,7,8,3',4'-pentamethoxylflavone (5-HPMF), one of representative PMFs in Caco-2 cells. Our results demonstrated that oleic acid and bile acid promoted secretion of chylomicrons in Caco-2 cells, with mean diameter ranged from 70 to 150 nm. The intracellular level of 5-HPMF increased 3-fold by co-incubation with the mixed micelle solution. Moreover, the basolateral level of 5-HPMF increased 3-fold due to enhanced chylomicron-mediated transport. Overall, our results demonstrated for the first time that the bioavailability of polymethoxyflavones can be enhanced by promoting their incorporation into chylomicrons.

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“…4DN was chemically synthesized as previously described. 15,20,21 Chemical structures of NOB and 4DN are illustrated in Figure 1A. The purity of NOB and 4DN is >98% according to the HPLC analysis as shown in Figure 1B Animals, Diets, and Treatments.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Inhibitory Effects of 4′-Demethylnobiletin, a Metabolite of Nobiletin, on 12-O-Tetradecanoylphorbol-13-acetate (TPA)-Induced Inflammation in Mouse Ears

Song

Rakariyatham

et al. 2015

J. Agric. Food Chem.

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Nobiletin (NOB) is major citrus flavonoid with many health-promoting benefits. We reported previously that 4'-demethylnobiletin (4DN), a major metabolite of NOB, significantly inhibited lipopolysaccharide (LPS)-stimulated inflammation in RAW 264.7 macrophages. In this study, we further studied the anti-inflammatory effects of 4DN in TPA-induced skin inflammation in mice. We demonstrated that topical application of 4DN decreased TPA-induced ear edema by >88 ± 4.77% in mice. This inhibitory effect was associated with inhibition on TPA-induced up-regulation of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Immunoblotting results showed that 4DN resulted in profound effects on multiple proteins related with inflammation and carcinogenesis. 4DN significantly decreased the expression levels of iNOS, COX-2, and MMP-9, suppressed phosphorylation of PI3K/Akt and ERK, and increased the levels of HO-1 and NQO1 in TPA-treated mice. Overall, the results demonstrated that 4DN had strong anti-inflammatory effects in vivo, which provided a scientific basis for using NOB to inhibit inflammation-driven diseases.

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Identification of novel bioactive metabolites of 5-demethylnobiletin in mice

Cited by 67 publications

References 32 publications

Anticancer Activities of Citrus Peel Polymethoxyflavones Related to Angiogenesis and Others

Anticancer Activities of Citrus Peel Polymethoxyflavones Related to Angiogenesis and Others

Enhanced lymphatic transport of bioactive lipids: cell culture study of polymethoxyflavone incorporation into chylomicrons

Inhibitory Effects of 4′-Demethylnobiletin, a Metabolite of Nobiletin, on 12-O-Tetradecanoylphorbol-13-acetate (TPA)-Induced Inflammation in Mouse Ears

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