Comparative metabolism of honokiol in mouse, rat, dog, monkey, and human hepatocytes

详细信息    查看全文

• 作者：Hyeon-Uk Jeong ; Ju-Hyun Kim ; Tae Yeon Kong ; Won Gu Choi…
• 关键词：Honokiol ; Hepatocytes ; Comparative metabolism ; UDP ; glucuronosyltransferases ; Sulfotransferases
• 刊名：Archives of Pharmacal Research
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：39
• 期：4
• 页码：516-530
• 全文大小：858 KB
• 参考文献：Bohmdorfer M, Maier-Salamon A, Taferner B, Reznicek G, Thalhammer T, Hering S, Hufner A, Schuhly W, Jager W (2011) In vitro metabolism and disposition of honokiol in rat and human livers. Eur J Pharm Sci 100:3506–3516CrossRef
  Bohnert T, Gan L-S (2010) The role of Frug metabolism in drug discovery. In: Lu C, Li AP (eds) Enzyme inhibition in drug discovery and development. Wiley, New York, pp 91–176
  Chao LK, Liao PC, Ho CL, Wang EI, Chuang CC, Chiu HW, Hung LB, Hua KF (2010) Anti-inflammatory bioactivities of honokiol through inhibition of protein kinase C, mitogen-activated protein kinase, and the NF-kappaB pathway to reduce LPS-induced TNFalpha and NO expression. J Agric Food Chem 58:3472–3478CrossRef PubMed
  Cui HS, Huang LS, Sok DE, Shin J, Kwon BM, Youn UJ, Bae K (2007) Protective action of honokiol, administered orally, against oxidative stress in brain of mice challenged with NMDA. Phytomedicine 14:696–700CrossRef PubMed
  Davies B, Morris T (1993) Physiological parameters in laboratory animals and humans. Pharm Res 10:1093–1095CrossRef PubMed
  Dikalov S, Losik T, Arbiser JL (2008) Honokiol is a potent scavenger of superoxide and peroxyl radicals. Biochem Pharmacol 76:589–596CrossRef PubMed PubMedCentral
  Dong Y, Tang M, Song H, Li R, Wang C, Ye H, Qiu N, Zhang Y, Chen L, Wei Y (2014) Characterization of metabolic profile of honokiol in rat feces using liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and (13)C stable isotope labeling. J Chromatogr B 953–954:20–29CrossRef
  Hoi CP, Ho YP, Baum L, Chow AH (2010) Neuroprotective effect of honokiol and magnolol, compounds from Magnolia officinalis, on beta-amyloid-induced toxicity in PC12 cells. Phytother Res 24:1538–1542CrossRef PubMed
  Hu H, Zhang XX, Wang YY, Chen SZ (2005) Honokiol inhibits arterial thrombosis through endothelial cell protection and stimulation of prostacyclin. Acta Pharmacol Sin 26:1063–1068CrossRef PubMed
  Joo J, Lee D, Wu Z, Shin JH, Lee HS, Kwon BM, Huh TL, Kim YW, Lee SJ, Kim TW, Lee T, Liu KH (2013) In vitro metabolism of obovatol and its effect on cytochrome P450 enzyme activities in human liver microsomes. Biopharm Drug Dispos 34:195–202CrossRef PubMed
  Kim BH, Cho JY (2008) Anti-inflammatory effect of honokiol is mediated by PI3 K/Akt pathway suppression. Acta Pharmacol Sin 29:113–122CrossRef PubMed
  Lai H, Tang M, Liu J, Dong Y, Qiu N, Li S, Ma L, Yang J, Song H, Zhang Y, Peng A, Chen L (2013) Identification of honokiol metabolites in rats by the method of stable isotope cluster technique and ultra-high performance liquid chromatography/quadrupole-time-of-flight mass spectrometry. J Chromatogr B 931:157–163CrossRef
  Lee SY, Cho JY (2009) Inhibitory effects of honokiol on LPS and PMA-induced cellular responses of macrophages and monocytes. BMB Rep 42:574–579CrossRef PubMed
  Lee SK, Kim DH, Yoo HH (2011a) Comparative metabolism of sildenafil in liver microsomes of different species by using LC/MS-based multivariate analysis. J Chromatogr B 879:3005–3011CrossRef
  Lee YJ, Lee YM, Lee CK, Jung JK, Han SB, Hong JT (2011b) Therapeutic applications of compounds in the Magnolia family. Pharmacol Ther 130:157–176CrossRef PubMed
  Lin YR, Chen HH, Ko CH, Chan MH (2006) Neuroprotective activity of honokiol and magnolol in cerebellar granule cell damage. Eur J Pharmacol 537:64–69CrossRef PubMed
  Lin YR, Chen HH, Lin YC, Ko CH, Chan MH (2009) Antinociceptive actions of honokiol and magnolol on glutamatergic and inflammatory pain. J Biomed Sci 16:94CrossRef PubMed PubMedCentral
  Liu J, Tang M, Lai H, Dong Y, Xie C, Ye H, Ma L, Qiu N, Li Y, Cai L, Chen L (2013) Identification of metabolites of honokiol in rat urine using 13C stable isotope labeling and liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. J Chromatogr A 1295:48–56CrossRef PubMed
  Matsui N, Takahashi K, Takeichi M, Kuroshita T, Noguchi K, Yamazaki K, Tagashira H, Tsutsui K, Okada H, Kido Y, Yasui Y, Fukuishi N, Fukuyama Y, Akagi M (2009) Magnolol and honokiol prevent learning and memory impairment and cholinergic deficit in SAMP8 mice. Brain Res 1305:108–117CrossRef PubMed
  Munroe ME, Arbiser JL, Bishop GA (2007) Honokiol, a natural plant product, inhibits inflammatory signals and alleviates inflammatory arthritis. J Immunol 179:753–763CrossRef PubMed
  Munroe ME, Businga TR, Kline JN, Bishop GA (2010) Anti-inflammatory effects of the neurotransmitter agonist Honokiol in a mouse model of allergic asthma. J Immunol 185:5586–5597CrossRef PubMed PubMedCentral
  Peters SA (2012) Physiologically-Based Pharmacokinetic (PBPK) modeling and simulations: principles, methods, and applications in the Pharmaceutical Industry. Wiley, New YorkCrossRef
  Riches Z, Stanley EL, Bloomer JC, Coughtrie MW (2009) Quantitative evaluation of the expression and activity of five major sulfotransferases (SULTs) in human tissues: the SULT “pie”. Drug Metab Dispos 37:2255–2261CrossRef PubMed PubMedCentral
  Rowland A, Miners JO, Mackenzie PI (2013) The UDP-glucuronosyltransferases: their role in drug metabolism and detoxification. Int J Biochem Cell Biol 45:1121–1132CrossRef PubMed
  Runge-Morris M, Kocarek TA (2009) Regulation of sulfotransferase and UDP-glucuronosyltransferase gene expression by the PPARs. PPAR Res 2009:728941CrossRef PubMed PubMedCentral
  Seo MS, Kim JH, Kim HJ, Chang KC, Park SW (2015) Honokiol activates the LKB1-AMPK signaling pathway and attenuates the lipid accumulation in hepatocytes. Toxicol Appl Pharmacol 284:113–124CrossRef PubMed
  Shen JL, Man KM, Huang PH, Chen WC, Chen DC, Cheng YW, Liu PL, Chou MC, Chen YH (2010) Honokiol and magnolol as multifunctional antioxidative molecules for dermatologic disorders. Molecules 15:6452–6465CrossRef PubMed
  Sheng YL, Xu JH, Shi CH, Li W, Xu HY, Li N, Zhao YQ, Zhang XR (2014) UPLC-MS/MS-ESI assay for simultaneous determination of magnolol and honokiol in rat plasma: application to pharmacokinetic study after administration emulsion of the isomer. J Ethnopharmacol 155:1568–1574CrossRef PubMed
  Sohlenius-Sternbeck AK (2006) Determination of the hepatocellularity number for human, dog, rabbit, rat and mouse livers from protein concentration measurements. Toxicol In Vitro 20:1582–1586CrossRef PubMed
  Spaulding SW, Smith TJ, Hinkle PM, Davis FB, Kung MP, Roth JA (1992) Studies on the biological activity of triiodothyronine sulfate. J Clin Endocrinol Metab 74:1062–1067PubMed
  Tsai TH, Chou CJ, Cheng FC, Chen CF (1994) Pharmacokinetics of honokiol after intravenous administration in rats assessed using high-performance liquid chromatography. J Chromatogr B 655:41–45CrossRef
  Wang X, Deng L, Cai L, Zhang X, Zheng H, Deng C, Duan X, Zhao X, Wei Y, Chen L (2011) Preparation, characterization, pharmacokinetics, and bioactivity of honokiol-in-hydroxypropyl-beta-cyclodextrin-in-liposome. J Pharm Sci 100:3357–3364CrossRef PubMed
  Wu X, Chen X, Hu Z (2003) High-performance liquid chromatographic method for simultaneous determination of honokiol and magnolol in rat plasma. Talanta 59:115–121CrossRef PubMed
  Xu Q, Yi LT, Pan Y, Wang X, Li YC, Li JM, Wang CP, Kong LD (2008) Antidepressant-like effects of the mixture of honokiol and magnolol from the barks of Magnolia officinalis in stressed rodents. Prog Neuropsychopharmacol Biol Psychiatry 32:715–725CrossRef PubMed
  Yi LT, Xu Q, Li YC, Yang L, Kong LD (2009) Antidepressant-like synergism of extracts from magnolia bark and ginger rhizome alone and in combination in mice. Prog Neuropsychopharmacol Biol Psychiatry 33:616–624CrossRef PubMed
  Yu HE, Oh SJ, Ryu JK, Kang JS, Hong JT, Jung JK, Han SB, Seo SY, Kim YH, Park SK, Kim HM, Lee K (2014) Pharmacokinetics and metabolism of 4-O-methylhonokiol in rats. Phytother Res 28:568–578CrossRef PubMed
  Zhang T, Haws P, Wu Q (2004) Multiple variable first exons: a mechanism for cell- and tissue-specific gene regulation. Genome Res 14:79–89CrossRef PubMed PubMedCentral
  Zhu L, Ge G, Zhang H, Liu H, He G, Liang S, Zhang Y, Fang Z, Dong P, Finel M, Yang L (2012) Characterization of hepatic and intestinal glucuronidation of magnolol: application of the relative activity factor approach to decipher the contributions of multiple UDP-glucuronosyltransferase isoforms. Drug Metab Dispos 40:529–538CrossRef PubMed
  
• 作者单位：Hyeon-Uk Jeong (1)
  Ju-Hyun Kim (1)
  Tae Yeon Kong (1)
  Won Gu Choi (1)
  Hye Suk Lee (1)
  
  1. Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, The Catholic University of Korea, Bucheon, 420-743, Republic of Korea
  
• 刊物主题：Pharmacy; Pharmacology/Toxicology;
• 出版者：Springer Netherlands
• ISSN：1976-3786

文摘

Honokiol has antitumor, antioxidative, anti-inflammatory, and antithrombotic effects. Here we aimed to identify the metabolic profile of honokiol in mouse, rat, dog, monkey, and human hepatocytes and to characterize the enzymes responsible for the glucuronidation and sulfation of honokiol. Honokiol had a high hepatic extraction ratio in all five species, indicating that it was extensively metabolized. A total of 32 metabolites, including 17 common and 15 different metabolites, produced via glucuronidation, sulfation, and oxidation of honokiol allyl groups were tentatively identified using liquid chromatography–high resolution quadrupole Orbitrap mass spectrometry. Glucuronidation of honokiol to M8 (honokiol-4-glucuronide) and M9 (honokiol-2′-glucuronide) was the predominant metabolic pathway in hepatocytes of all five species; however, interspecies differences between 4- and 2′-glucuronidation of honokiol were observed. UGT1A1, 1A8, 1A9, 2B15, and 2B17 played major roles in M8 formation, whereas UGT1A7 and 1A9 played major roles in M9 formation. Human cDNA-expressed SULT1C4 played a major role in M10 formation (honokiol-2′-sulfate), whereas SULT1A1*1, 1A1*2, and 1A2 played major roles in M11 formation (honokiol-4-sulfate). In conclusion, honokiol metabolism showed interspecies differences.