Identification of novel bioactive metabolites of 5-demethylnobiletin in mice

Molecular Nutrition and Food Research

Volumn 57, Issue 11, 2013, Pages 1999-2007

  Zheng, Jinkai ^a   Song, Mingyue ^a   Dong, Ping ^a   Qiu, Peiju ^a,b   Guo, Shanshan ^a   Zhong, Zhimei ^a,c   Li, Shiming ^d   Ho, Chi Tang ^d   Xiao, Hang ^a  

^a UNIVERSITY OF MASSACHUSETTS   (United States)

^b OCEAN UNIVERSITY OF CHINA   (China)

^c INNER MONGOLIA AGRICULTURAL UNIVERSITY   (China)

^d RUTGERS UNIVERSITY   (United States)

Author keywords

5,3 Didemethylnobiletin; 5 Demethylnobiletin; Cancer inhibition; Metabolites

Indexed keywords

5 O DEMETHYLNOBILETIN; 5-O-DEMETHYLNOBILETIN; FLAVONE DERIVATIVE; PLANT EXTRACT;

5,3′-DIDEMETHYLNOBILETIN; 5-DEMETHYLNOBILETIN; ANIMAL; ARTICLE; BIOTRANSFORMATION; CANCER INHIBITION; CELL SURVIVAL; CHEMISTRY; CITRUS; COLON TUMOR; DRUG EFFECT; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; LIQUID CHROMATOGRAPHY; MALE; MASS SPECTROMETRY; METABOLITES; MOUSE; ORAL DRUG ADMINISTRATION; TUMOR CELL LINE; URINE;

5,3′-DIDEMETHYLNOBILETIN; 5-DEMETHYLNOBILETIN; CANCER INHIBITION; METABOLITES;

ADMINISTRATION, ORAL; ANIMALS; BIOTRANSFORMATION; CELL LINE, TUMOR; CELL SURVIVAL; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CHROMATOGRAPHY, LIQUID; CITRUS; COLONIC NEOPLASMS; FLAVONES; HUMANS; MALE; MASS SPECTROMETRY; MICE; PLANT EXTRACTS;

EID: 84886789774     PISSN: 16134125     EISSN: 16134133     Source Type: Journal    
DOI: 10.1002/mnfr.201300211     Document Type: Article

References (34)

1. Li, S., Lo, C. Y., Ho, C. T., Hydroxylated polymethoxyflavones and methylated flavonoids in sweet orange (Citrus sinensis) peel. J. Agric. Food Chem. 2006, 54, 4176-4185.
2. Li, S. M., Pan, M. H., Lo, C. Y., Tan, D. et al., Chemistry and health effects of polymethoxyflavones and hydroxylated polymethoxyflavones. J. Funct. Foods 2009, 1, 2-12.
3. Xiao, H., Yang, C. S., Li, S., Jin, H. et al., Monodemethylated polymethoxyflavones from sweet orange (Citrus sinensis) peel inhibit growth of human lung cancer cells by apoptosis. Mol. Nutr. Food Res. 2009, 53, 398-406.
4. Qiu, P., Dong, P., Guan, H., Li, S. et al., Inhibitory effects of 5-hydroxy polymethoxyflavones on colon cancer cells. Mol. Nutr. Food Res. 2010, 54 (Suppl 2), S244-S252.
5. Qiu, P., Guan, H., Dong, P., Guo, S. et al., The inhibitory effects of 5-hydroxy-3, 6, 7, 8, 3′, 4′-hexamethoxyflavone on human colon cancer cells. Mol. Nutr. Food Res. 2011, 55, 1523-1532.
6. Qiu, P., Guan, H., Dong, P., Li, S. et al., The p53-, Bax- and p21-dependent inhibition of colon cancer cell growth by 5-hydroxy polymethoxyflavones. Mol. Nutr. Food Res. 2011, 55, 613-622.
7. Sergeev, I. N., Ho, C. T., Li, S., Colby, J. et al., Apoptosis-inducing activity of hydroxylated polymethoxyflavones and polymethoxyflavones from orange peel in human breast cancer cells. Mol. Nutr. Food Res. 2007, 51, 1478-1484.
8. Pan, M. H., Lai, Y. S., Lai, C. S., Wang, Y. J. et al., 5-Hydroxy-3, 6, 7, 8, 3′, 4′-hexamethoxyflavone induces apoptosis through reactive oxygen species production, growth arrest and DNA damage-inducible gene 153 expression, and caspase activation in human leukemia cells. J. Agric. Food Chem. 2007, 55, 5081-5091.
9. Bas, E., Recio, M. C., Giner, R. M., Manez, S. et al., Anti-inflammatory activity of 5-O-demethylnobiletin, a polymethoxyflavone isolated from Sideritis tragoriganum. Planta Med. 2006, 72, 136-142.
10. Yen, J. H., Weng, C. Y., Li, S., Lo, Y. H. et al., Citrus flavonoid 5-demethylnobiletin suppresses scavenger receptor expression in THP-1 cells and alters lipid homeostasis in HepG2 liver cells. Mol. Nutr. Food Res. 2011, 55, 733-748.
11. Yang, M., Cheng, C. R., Yang, J. L., Guo, D. A., Metabolite profiling and characterization for medicinal herbal remedies. Curr. Drug. Metab. 2012, 13, 535-557.
12. Monagas, M., Urpi-Sarda, M., Sanchez-Patan, F., Llorach, R. et al., Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. Food Funct. 2010, 1, 233-253.
13. Magee, P. J., Session 3: influences of food constituents on gut health is equol production beneficial to health? P. Nutr. Soc. 2011, 70, 10-18.
14. Lotito, S. B., Zhang, W. J., Yang, C. S., Crozier, A. et al., Metabolic conversion of dietary flavonoids alters their anti-inflammatory and antioxidant properties. Free Radic. Bio. Med. 2011, 51, 454-463.
15. Matthies, A., Loh, G., Blaut, M., Braune, A., Daidzein and genistein are converted to equol and 5-hydroxy-equol by human intestinal Slackia isoflavoniconvertens in gnotobiotic rats. J. Nutr. 2012, 142, 40-46.
16. Setchell, K. D., Clerici, C., Equol: pharmacokinetics and biological actions. J. Nutr. 2010, 140, 1363S-1368S.
17. Nagase, H., Omae, N., Omori, A., Nakagawasai, O. et al., Nobiletin and its related flavonoids with CRE-dependent transcription-stimulating and neuritegenic activities. Biochem. Biophys. Res. Commun. 2005, 337, 1330-1336.
18. Wang, K. W., Zhang, H., Positive electrospray ionization tandem mass spectrometry of polymethoxylated flavones. Rapid. Commun. Mass. Spectrom. 2009, 23, 2107-2111.
19. Wollenweber, E., Dorr, M., Rivera, D., Roitman, J. N., Externally accumulated flavonoids in three Mediterranean Ononis species. Z. Naturforsch. C 2003, 58, 771-775.
20. Ho, C. T., Bai, N. S., He, K., Zhou, Z. et al., Flavonoids from Rabdosia rubescens exert anti-inflammatory and growth inhibitory effect against human leukemia HL-60 cells. Food Chem. 2010, 122, 831-835.
21. Li, S., Wang, Z., Sang, S., Huang, M. T. et al., Identification of nobiletin metabolites in mouse urine. Mol. Nutr. Food Res. 2006, 50, 291-299.
22. Dong, P., Qiu, P., Zhu, Y., Li, S. et al., Simultaneous determination of four 5-hydroxy polymethoxyflavones by reversed-phase high performance liquid chromatography with electrochemical detection. J. Chromatogr. A 2010, 1217, 642-647.
23. Feng, W., Yang, J., Xu, X., Liu, Q., Quantitative determination of lanostane triterpenes in Fomes officinalis and their fragmentation study by HPLC-ESI. Phytochem. Anal. 2010, 21, 531-538.
24. Li, S., Wang, Y., Wang, Z., Xiao, H. et al., Quantitative analysis of hydroxylated polymethoxyflavones by high-performance liquid chromatography. Biomed. Chromatogr. 2010, 24, 838-845.
25. Qiu, P., Guan, H., Dong, P., Guo, S. et al., The inhibitory effects of 5-hydroxy-3, 6, 7, 8, 3′, 4′-hexamethoxyflavone on human colon cancer cells. Mol. Nutr. Food Res. 2011, 55, 1523-1532.
26. Yasuda, T., Yoshimura, Y., Yabuki, H., Nakazawa, T. et al., Urinary metabolites of nobiletin orally administered to rats. Chem. Pharm. Bull. (Tokyo) 2003, 51, 1426-1428.
27. Li, S., Sang, S., Pan, M. H., Lai, C. S. et al., Anti-inflammatory property of the urinary metabolites of nobiletin in mouse. Bioorg. Med. Chem. Lett. 2007, 17, 5177-5181.
28. Li, S., Pan, M. H., Lai, C. S., Lo, C. Y. et al., Isolation and syntheses of polymethoxyflavones and hydroxylated polymethoxyflavones as inhibitors of HL-60 cell lines. Bioorg. Med. Chem. 2007, 15, 3381-3389.
29. Koga, N., Ohta, C., Kato, Y., Haraguchi, K. et al., In vitro metabolism of nobiletin, a polymethoxy-flavonoid, by human liver microsomes and cytochrome P450. Xenobiotica 2011, 41, 927-933.
30. Surichan, S., Androutsopoulos, V. P., Sifakis, S., Koutala, E. et al., Bioactivation of the citrus flavonoid nobiletin by CYP1 enzymes in MCF7 breast adenocarcinoma cells. Food Chem. Toxicol. 2012, 50, 3320-3328.
31. Oshitari, T., Okuyama, Y., Miyata, Y., Kosano, H. et al., Nobiletin metabolites: synthesis and inhibitory activity against matrix metalloproteinase-9 production. Bioorg. Med. Chem. Lett. 2011, 21, 4540-4544.
32. Gosslau, A., Li, S. M., Ho, C. T., Chen, K. Y. et al., The importance of natural product characterization in studies of their anti-inflammatory activity. Mol. Nutr. Food Res. 2011, 55, 74-82.
33. Yen, J. H., Weng, C. Y., Li, S. M., Lo, Y. H. et al., Citrus flavonoid 5-demethylnobiletin suppresses scavenger receptor expression in THP-1 cells and alters lipid homeostasis in HepG2 liver cells. Mol. Nutr. Food Res. 2011, 55, 733-748.
34. Oshitari, T., Okuyama, Y., Miyata, Y., Kosano, H. et al., B-Ring-modified and/or 5-demethylated nobiletin congeners: inhibitory activity against pro-MMP-9 production. Bioorgan. Med. Chem. 2011, 19, 7085-7092.