Abstract
We recently demonstrated that nobiletin, a citrus flavonoid, exhibits anti-dementia action in animals. However, no determination methods for the content of nobiletin with beneficial action in the brain of nobiletin-administered animals have been developed, nor has its pharmacokinetics been revealed completely. Here, we established the high-performance liquid chromatography/photodiode array detection method for nobiletin determination using Bond Elut C18 SPE cartridges for extraction, where the calibration curve was linear over 0.025–10 ng, with coefficient of variation of less than 6.76%. This method enabled us to determine pharmacokinetic parameters of nobiletin given intraperitoneally or per os in the brain of mice.
Similar content being viewed by others
References
Nagase H, Yamakuni T, Matsuzaki K, Maruyama Y, Kasahara J, Hinohara Y, Kondo S, Mimaki Y, Sashida Y, Tank AW, Fukunaga K, Ohizumi Y (2005) Mechanism of neurotrophic action of nobiletin in PC12D cells. Biochemistry 44(42):13683–13691
Nagase H, Omae N, Omori A, Nakagawasai O, Tadano T, Yokosuka A, Sashida Y, Mimaki Y, Yamakuni T, Ohizumi Y (2005) Nobiletin and its related flavonoids with CRE-dependent transcription-stimulating and neuritegenic activities. Biochem Biophys Res Commun 337(4):1330–1336
Matsuzaki K, Miyazaki K, Sakai S, Yawo H, Nakata N, Moriguchi S, Fukunaga K, Yokosuka A, Sashida Y, Mimaki Y, Yamakuni T, Ohizumi Y (2008) Nobiletin, a citrus flavonoid with neurotrophic action, augments protein kinase A-mediated phosphorylation of the AMPA receptor subunit, GluR1, and the postsynaptic receptor response to glutamate in murine hippocampus. Eur J Pharmacol 578(2–3):194–200
Nakajima A, Yamakuni T, Haraguchi M, Omae N, Song SY, Kato C, Nakagawasai O, Tadano T, Yokosuka A, Mimaki Y, Sashida Y, Ohizumi Y (2007) Nobiletin, a citrus flavonoid that improves memory impairment, rescues bulbectomy-induced cholinergic neurodegeneration in mice. J Pharmacol Sci 105(1):122–126
Nakajima A, Yamakuni T, Matsuzaki K, Nakata N, Onozuka H, Yokosuka A, Sashida Y, Mimaki Y, Ohizumi Y (2007) Nobiletin, a citrus flavonoid, reverses learning impairment associated with N-methyl-d-aspartate receptor antagonism by activation of extracellular signal-regulated kinase signaling. J Pharmacol Exp Ther 321(2):784–790
Matsuzaki K, Yamakuni T, Hashimoto M, Haque AM, Shido O, Mimaki Y, Sashida Y, Ohizumi Y (2006) Nobiletin restoring beta-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer’s disease model rats. Neurosci Lett 400(3):230–234
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(3):739–744
Yamamoto Y, Shioda N, Han F, Moriguchi S, Nakajima A, Yokosuka A, Mimaki Y, Sashida Y, Yamakuni T, Ohizumi Y, Ohizumi Y, Fukunaga K (2009) Nobiletin improves brain ischemia-induced learning and memory deficits through stimulation of CaMKII and CREB phosphorylation. Brain Res 1295:218–229
Wang Z, Li S, Ferguson S, Goodnow R, Ho CT (2008) Validated reversed phase LC method for quantitative analysis of polymethoxyflavones in citrus peel extracts. J Sep Sci 31(1):30–37
Ding L, Luo X, Tang F, Yuan J, Liu Q, Yao S (2007) Simultaneous determination of flavonoid and alkaloid compounds in Citrus herbs by high-performance liquid chromatography-photodiode array detection-electrospray mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 857(2):202–209
Wang D, Wang J, Huang X, Tu Y, Ni K (2007) Identification of polymethoxylated flavones from green tangerine peel (Pericarpium Citri Reticulatae Viride) by chromatographic and spectroscopic techniques. J Pharm Biomed Anal 44(1):63–69
Wang Z, Li S, Jonca M, Lambros T, Ferguson S, Goodnow R, Ho CT (2006) Comparison of supercritical fluid chromatography and liquid chromatography for the separation of urinary metabolites of nobiletin with chiral and non-chiral stationary phases. Biomed Chromatogr 20(11):1206–1215
Li S, Wang Z, Sang S, Huang MT, Ho CT (2006) Identification of nobiletin metabolites in mouse urine. Mol Nutr Food Res 50(3):291–299
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(18):5177–5181
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(12):1426–1428
Faria A, Pestana D, Teixeira D, Azevedo J, De Freitas V, Mateus N, Calhau C (2010) Flavonoid transport across RBE4 cells: a blood-brain barrier model. Cell Mol Biol Lett 15(2):234–241
Yan B, Wang W, Zhang L, Xing D, Wang D, Du L (2006) Determination of puerarin in rat cortex by high-performance liquid chromatography after intravenous administration of Puerariae flavonoids. Biomed Chromatogr 20(2):180–184
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(PDF 36 kb)
Rights and permissions
About this article
Cite this article
Saigusa, D., Shibuya, M., Jinno, D. et al. High-performance liquid chromatography with photodiode array detection for determination of nobiletin content in the brain and serum of mice administrated the natural compound. Anal Bioanal Chem 400, 3635–3641 (2011). https://doi.org/10.1007/s00216-011-5031-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-011-5031-2