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Xenobiotica
the fate of foreign compounds in biological systems
Volume 41, 2011 - Issue 11
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General Xenobiochemistry

In vitro metabolism of nobiletin, a polymethoxy-flavonoid, by human liver microsomes and cytochrome P450

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Pages 927-933 | Received 08 Apr 2011, Accepted 30 May 2011, Published online: 05 Jul 2011

References

  • Al Rahim M, Nakajima A, Saigusa D, Tetsu N, Maruyama Y, Shibuya M, Yamakoshi H, Tomioka Y, Iwabuchi Y, Ohizumi Y, Yamakuni T. (2009). 4′-Demethylnobiletin, a bioactive metabolite of nobiletin enhancing PKA/ERK/CREB signaling, rescues learning impairment associated with NMDA receptor antagonism via stimulation of the ERK cascade. Biochemistry 48:7713–7721.
  • Breinholt VM, Offord EA, Brouwer C, Nielsen SE, Brøsen K, Friedberg T. (2002). In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids. Food Chem Toxicol 40:609–616.
  • Breinholt VM, Rasmussen SE, Brøsen K, Friedberg TH. (2003). In vitro metabolism of genistein and tangeretin by human and murine cytochrome P450s. Pharmacol Toxicol 93:14–22.
  • Eguchi A, Murakami A, Li S, Ho CT, Ohigashi H. (2007). Suppressive effects of demethylated metabolites of nobiletin on phorbol ester-induced expression of scavenger receptor genes in THP-1 human monocytic cells. Biofactors 31:107–116.
  • Guengerich FP. (1997). Comparisons of catalytic selectivity of cytochrome P450 subfamily enzymes from different species. Chem Biol Interact 106:161–182.
  • Guengerich FP. (2006). Cytochrome P450s and other enzymes in drug metabolism and toxicity. AAPS J 8:E101–E111.
  • Hu M, Krausz K, Chen J, Ge X, Li J, Gelboin HL, Gonzalez FJ. (2003). Identification of CYP1A2 as the main isoform for the phase I hydroxylated metabolism of genistein and a prodrug converting enzyme of methylated isoflavones. Drug Metab Dispos 31:924–931.
  • Ishiwa J, Sato T, Mimaki Y, Sashida Y, Yano M, Ito A. (2000). A citrus flavonoid, nobiletin, suppresses production and gene expression of matrix metalloproteinase 9/gelatinase B in rabbit synovial fibroblasts. J Rheumatol 27:20–25.
  • Kawabata K, Murakami A, Ohigashi H. (2005). Nobiletin, a citrus flavonoid, down-regulates matrix metalloproteinase-7 (matrilysin) expression in HT-29 human colorectal cancer cells. Biosci Biotechnol Biochem 69:307–314.
  • Koga N, Matsuo M, Ohta C, Haraguchi K, Matsuoka M, Kato Y, Ishii T, Yano M, Ohta H. (2007). Comparative study on nobiletin metabolism with liver microsomes from rats, guinea pigs and hamsters and rat cytochrome P450. Biol Pharm Bull 30:2317–2323.
  • Kohno H, Yoshitani S, Tsukio Y, Murakami A, Koshimizu K, Yano M, Tokuda H, Nishino H, Ohigashi H, Tanaka T. (2001). Dietary administration of citrus nobiletin inhibits azoxymethane-induced colonic aberrant crypt foci in rats. Life Sci 69:901–913.
  • Kulling SE, Honig DM, Metzler M. (2001). Oxidative metabolism of the soy isoflavones daidzein and genistein in humans in vitro and in vivo. J Agric Food Chem 49:3024–3033.
  • Lai CS, Li S, Chai CY, Lo CY, Dushenkov S, Ho CT, Pan MH, Wang YJ. (2008). Anti-inflammatory and antitumor promotional effects of a novel urinary metabolite, 3′,4′-didemethylnobiletin, derived from nobiletin. Carcinogenesis 29:2415–2424.
  • Li S, Sang S, Pan MH, Lai CS, Lo CY, Yang CS, Ho CT. (2007). Anti-inflammatory property of the urinary metabolites of nobiletin in mouse. Bioorg Med Chem Lett 17:5177–5181.
  • Li S, Wang Z, Sang S, Huang MT, Ho CT. (2006). Identification of nobiletin metabolites in mouse urine. Mol Nutr Food Res 50:291–299.
  • Lin N, Sato T, Takayama Y, Mimaki Y, Sashida Y, Yano M, Ito A. (2003). Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages. Biochem Pharmacol 65:2065–2071.
  • Lo YH, Pan MH, Li S, Yen JH, Kou MC, Ho CT, Wu MJ. (2010). Nobiletin metabolite, 3′,4′-dihydroxy-5,6,7,8-tetramethoxyflavone, inhibits LDL oxidation and down-regulates scavenger receptor expression and activity in THP-1 cells. Biochim Biophys Acta 1801:114–126.
  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. (1951). Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275.
  • Minagawa A, Otani Y, Kubota T, Wada N, Furukawa T, Kumai K, Kameyama K, Okada Y, Fujii M, Yano M, Sato T, Ito A, Kitajima M. (2001). The citrus flavonoid, nobiletin, inhibits peritoneal dissemination of human gastric carcinoma in SCID mice. Jpn J Cancer Res 92:1322–1328.
  • Murakami A, Nakamura Y, Ohto Y, Yano M, Koshiba T, Koshimizu K, Tokuda H, Nishino H, Ohigashi H. (2000a). Suppressive effects of citrus fruits on free radical generation and nobiletin, an anti-inflammatory polymethoxyflavonoid. Biofactors 12:187–192.
  • Murakami A, Nakamura Y, Torikai K, Tanaka T, Koshiba T, Koshimizu K, Kuwahara S, Takahashi Y, Ogawa K, Yano M, Tokuda H, Nishino H, Mimaki Y, Sashida Y, Kitanaka S, Ohigashi H. (2000b). Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice. Cancer Res 60:5059–5066.
  • Nagase H, Omae N, Omori A, Nakagawasai O, Tadano T, Yokosuka A, Sashida Y, Mimaki Y, Yamakuni T, Ohizumi Y. (2005a). Nobiletin and its related flavonoids with CRE-dependent transcription-stimulating and neuritegenic activities. Biochem Biophys Res Commun 337:1330–1336.
  • Nagase H, Yamakuni T, Matsuzaki K, Maruyama Y, Kasahara J, Hinohara Y, Kondo S, Mimaki Y, Sashida Y, Tank AW, Fukunaga K, Ohizumi Y. (2005b). Mechanism of neurotrophic action of nobiletin in PC12D cells. Biochemistry 44:13683–13691.
  • Nielsen SE, Breinholt V, Justesen U, Cornett C, Dragsted LO. (1998). In vitro biotransformation of flavonoids by rat liver microsomes. Xenobiotica 28:389–401.
  • Nogata Y, Sakamoto K, Shiratsuchi H, Ishii T, Yano M, Ohta H. (2006). Flavonoid composition of fruit tissues of citrus species. Biosci Biotechnol Biochem 70:178–192.
  • Onozuka H, Nakajima A, Matsuzaki K, Shin RW, Ogino K, Saigusa D, Tetsu N, Yokosuka A, Sashida Y, Mimaki Y, Yamakuni T, Ohizumi Y. (2008). Nobiletin, a citrus flavonoid, improves memory impairment and Abeta pathology in a transgenic mouse model of Alzheimer’s disease. J Pharmacol Exp Ther 326:739–744.
  • Pelkonen O, Mäenpää J, Taavitsainen P, Rautio A, Raunio H. (1998). Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotica 28:1203–1253.
  • Roberts-Kirchhoff ES, Crowley JR, Hollenberg PF, Kim H. (1999). Metabolism of genistein by rat and human cytochrome P450s. Chem Res Toxicol 12:610–616.
  • Shimada T, Fujii-Kuriyama Y. (2004). Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and 1B1. Cancer Sci 95:1–6.
  • Shimada T, Gillam EM, Sutter TR, Strickland PT, Guengerich FP, Yamazaki H. (1997). Oxidation of xenobiotics by recombinant human cytochrome P450 1B1. Drug Metab Dispos 25:617–622.
  • Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. (1994). Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414–423.
  • Silva ID, Rodrigues AS, Gaspar J, Maia R, Laires A, Rueff J. (1997). Involvement of rat cytochrome 1A1 in the biotransformation of kaempferol to quercetin: relevance to the genotoxicity of kaempferol. Mutagenesis 12:383–390.
  • Tanaka S, Sato T, Akimoto N, Yano M, Ito A. (2004). Prevention of UVB-induced photoinflammation and photoaging by a polymethoxy flavonoid, nobiletin, in human keratinocytes in vivo and in vitro. Biochem Pharmacol 68:433–439.
  • Walle UK, Walle T. (2007). Bioavailable flavonoids: cytochrome P450-mediated metabolism of methoxyflavones. Drug Metab Dispos 35:1985–1989.
  • Yasuda T, Yoshimura Y, Yabuki H, Nakazawa T, Ohsawa K, Mimaki Y, Sashida Y. (2003). Urinary metabolites of nobiletin orally administered to rats. Chem Pharm Bull 51:1426–1428.

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