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Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Research Article

Pharmacokinetics and Tissue Distribution of Isovitexin-2''-O-β-D-glucopyranoside (IVG) in Sprague-Dawley Rats

Author(s): Xiaotong Zhao, Leilei Fang, Tan Yang, Yanqing Zhang* and Junbo Xie*

Volume 24, Issue 9, 2023

Published on: 28 September, 2023

Page: [656 - 666] Pages: 11

DOI: 10.2174/0113892002263771230920092659

Price: $65

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Abstract

Background: Isovitexin-2"-O-D-glucopyranoside (IVG) has been known to exhibit sedative and hypnotic effects. However, there is little understanding of the in vivo pharmacokinetics and tissue distribution of IVG.

Objective: This study aimed to investigate the pharmacokinetics and tissue distribution of IVG.

Methods: The study employed an HPLC–ESI-MS/MS method to analyze the pharmacokinetics and tissue distribution of IVG. Results: Under mass spectrometry, IVG and internal standard (IS) showed strong negative ionization signals. MRM analysis chose ion transitions m/z 593.3 → 293.0 (IVG) and m/z 579.8 → 271.4 (IS). Method validation indicated high precision, accuracy, and reliability with a quantitation limit under 20 ng/mL. After intravenously administering 5.0 mg/kg of IVG, rapid clearance from rat plasma was observed, with a half-life (t1/2) of 3.49 ± 0.99 h and a clearance rate of 54.53 ± 11.90 mL/kg/h. The area under the curve (AUC0-12h) of 37.79 ± 7.65 μg·h/mL indicated a brisk metabolic rate. Evaluating the tissue distribution, the highest accumulation was seen in the liver (30.32 ± 3.06 μg/g), followed by the kidney (20.58 ± 2.12 μg/g) and intestine (6.69 ± 0.93 μg/g), suggesting a propensity for IVG to concentrate in these tissues. Importantly, the presence of IVG in the brain underlines its potential to traverse the blood-brain barrier. These findings revealed that following intravenous administration, IVG was swiftly and broadly distributed throughout various rat tissues.

Conclusion: This study provides valuable information on the pharmacokinetics and tissue distribution of IVG, implicating its potential as a novel and effective drug candidate for sedative and anxiolytic treatment.

Graphical Abstract

[1]
Liu, S.J.; Lv, Y.P.; Tang, Z.S.; Zhang, Y.; Xu, H.B.; Zhang, D.B.; Cui, C.L.; Liu, H.B.; Sun, H.H.; Song, Z.X.; Wei, S-M. Ziziphus jujuba Mill., a plant used as medicinal food: A review of its phytochemistry, pharmacology, quality control and future research. Phytochem. Rev., 2021, 20(3), 507-541.
[http://dx.doi.org/10.1007/s11101-020-09709-1]
[2]
Fang, X.S.; Hao, J.F.; Zhou, H.Y.; Zhu, L.X.; Wang, J.H.; Song, F.Q. Pharmacological studies on the sedative-hypnotic effect of Semen Ziziphi spinosae (Suanzaoren) and Radix et Rhizoma Salviae miltiorrhizae (Danshen) extracts and the synergistic effect of their combinations. Phytomedicine, 2010, 17(1), 75-80.
[http://dx.doi.org/10.1016/j.phymed.2009.07.004] [PMID: 19682877]
[3]
Jiang, J.G.; Huang, X.J.; Chen, J.; Lin, Q.S. Comparison of the sedative and hypnotic effects of flavonoids, saponins, and polysaccharides extracted from Semen Ziziphus jujube. Nat. Prod. Res., 2007, 21(4), 310-320.
[http://dx.doi.org/10.1080/14786410701192827] [PMID: 17479419]
[4]
Ko, S.Y.; Lee, H.E.; Park, S.J.; Jeon, S.J.; Kim, B.; Gao, Q.; Jang, D.S.; Ryu, J.H. Spinosin, a C-glucosylflavone, from Zizyphus jujuba var. spinosa ameliorates aβ1–42 oligomer-induced memory impairment in mice. Biomol. Ther., 2015, 23(2), 156-164.
[http://dx.doi.org/10.4062/biomolther.2014.110] [PMID: 25767684]
[5]
Liu, J.; Zhai, W.M.; Yang, Y.X.; Shi, J.L.; Liu, Q.T.; Liu, G.L.; Fang, N.; Li, J.; Guo, J.Y. GABA and 5-HT systems are implicated in the anxiolytic-like effect of spinosin in mice. Pharmacol. Biochem. Behav., 2015, 128, 41-49.
[http://dx.doi.org/10.1016/j.pbb.2014.11.003] [PMID: 25449359]
[6]
Yang, T.; Fang, L.; Lin, T.; Li, J.; Zhang, Y.; Zhou, A.; Xie, J. Ultrasonicated sour Jujube seed flavonoids extract exerts ameliorative antioxidant capacity and reduces Aβ-induced toxicity in Caenorhabditis elegans. J. Ethnopharmacol., 2019, 239, 111886.
[http://dx.doi.org/10.1016/j.jep.2019.111886] [PMID: 31026552]
[7]
Lin, C.M.; Huang, S.T.; Liang, Y.C.; Lin, M.S.; Shih, C.M.; Chang, Y.C.; Chen, T.Y.; Chen, C.T. Isovitexin suppresses lipopolysaccharide-mediated inducible nitric oxide synthase through inhibition of NF-kappa B in mouse macrophages. Planta Med., 2005, 71(8), 748-753.
[http://dx.doi.org/10.1055/s-2005-871287] [PMID: 16142640]
[8]
Yuan, K.; Zhou, W.; Zhou, J.; Yang, P.; Zhang, J. Studies on the active components and antioxidant activities of the extracts of Mimosa pudica Linn. from southern China. Pharmacogn. Mag., 2011, 7(25), 35-39.
[http://dx.doi.org/10.4103/0973-1296.75899] [PMID: 21472077]
[9]
Cheng, G.; Bai, Y.; Zhao, Y.; Tao, J.; Liu, Y.; Tu, G.; Ma, L.; Liao, N.; Xu, X. Flavonoids from Ziziphus jujuba Mill var. spinosa. Tetrahedron, 2000, 56(45), 8915-8920.
[http://dx.doi.org/10.1016/S0040-4020(00)00842-5]
[10]
Zhang, L.; Xu, Z.L.; Wu, C.F.; Yang, J.Y.; Kano, Y.; Yuan, D. Two new flavonoid glycosides from Semen Ziziphi Spinosae. J. Asian Nat. Prod. Res., 2012, 14(2), 121-128.
[http://dx.doi.org/10.1080/10286020.2011.637491] [PMID: 22296152]
[11]
KEGG. Flavone and flavonol biosynthesis; Kanehisa Laboratories, 2018.
[12]
Bao, K.; Li, P.; Li, H.; Qi, L. Simultaneous determination of flavonoids and saponins in Semen Ziziphi spinosae (Suanzaoren) by high performance liquid chromatography with evaporative light scattering detection. Chinese J. Nat. Med., 2009, 7(1), 47-53.
[http://dx.doi.org/10.3724/SP.J.1009.2009.00047]
[13]
Niu, C.Y.; Wu, C.S.; Sheng, Y.X.; Zhang, J.L. Identification and characterization of flavonoids from Semen zizyphi spinosae by high-performance liquid chromatography/linear ion trap FTICR hybrid mass spectrometry. J. Asian Nat. Prod. Res., 2010, 12(4), 300-312.
[http://dx.doi.org/10.1080/10286021003752284] [PMID: 20419541]
[14]
Zhao, A.H.; Zhang, Y.B.; Yang, X.W. Simultaneous determination and pharmacokinetics of sixteen Angelicae dahurica coumarins in vivo by LC–ESI-MS/MS following oral delivery in rats. Phytomedicine, 2016, 23(10), 1029-1036.
[http://dx.doi.org/10.1016/j.phymed.2016.06.015] [PMID: 27444348]
[15]
Qiao, L.; Liu, Y.; Chen, X.; Xie, J.; Zhang, Y.; Yang, K.; Zhou, H.; Duan, Y.; Zheng, W.; Xie, W.A. HPLC-MS/MS method for determination of 6′′′-feruloylspinosin in rat plasma and tissues: Pharmacokinetics and tissue distribution study. J. Pharm. Biomed. Anal., 2016, 121, 77-83.
[http://dx.doi.org/10.1016/j.jpba.2016.01.005] [PMID: 26780157]
[16]
Zhang, Y.; Zhang, Y.; Zhang, K.; Ma, G.; Zhang, M.; Xie, J. Degradation kinetics of jujuboside b by rat intestinal flora in vitro with an RRLC-MS-MS method. J. Chromatogr. Sci., 2014, 52(7), 691-696.
[http://dx.doi.org/10.1093/chromsci/bmt100] [PMID: 23828910]
[17]
Food, U.; Administration, D. Bioanalytical method validation.Guidance for industry; , 2001. Available from:http://www. fda.gov/cder/guidance/4252fnl. htm
[18]
Bressolle, F.; Bromet-Petit, M.; Audran, M. Validation of liquid chromatographic and gas chromatographic methods Applications to pharmacokinetics. J. Chromatogr., Biomed. Appl., 1996, 686(1), 3-10.
[http://dx.doi.org/10.1016/S0378-4347(96)00088-6] [PMID: 8953186]
[19]
Nirogi, R.; Kandikere, V.; Mudigonda, K.; Komarneni, P.; Aleti, R.; Boggavarapu, R. Sensitive liquid chromatography tandem mass spectrometry method for the quantification of sitagliptin, a DPP-4 inhibitor, in human plasma using liquid–liquid extraction. Biomed. Chromatogr., 2008, 22(2), 214-222.
[http://dx.doi.org/10.1002/bmc.926] [PMID: 17939170]
[20]
Tiwari, G.; Tiwari, R. Bioanalytical method validation: An updated review. Pharm. Methods, 2010, 1(1), 25-38.
[http://dx.doi.org/10.4103/2229-4708.72226] [PMID: 23781413]
[21]
Draghici, S.; Khatri, P.; Eklund, A.; Szallasi, Z. Reliability and reproducibility issues in DNA microarray measurements. Trends Genet., 2006, 22(2), 101-109.
[http://dx.doi.org/10.1016/j.tig.2005.12.005] [PMID: 16380191]
[22]
Battal, D. Aktaş Süküroğlu, A.; Alkaş F.B.; Ünlüsayin, İ,. A rapid, precise, and sensitive lc-ms/ms method for the quantitative determination of urinary dopamine levels via a simple liquid-liquid extraction technique. Turk. J. Pharmaceut. Sci., 2021, 18(6), 761-769.
[http://dx.doi.org/10.4274/tjps.galenos.2021.60486] [PMID: 34979741]
[23]
Oddoze, C.; Lombard, E.; Portugal, H. Stability study of 81 analytes in human whole blood, in serum and in plasma. Clin. Biochem., 2012, 45(6), 464-469.
[http://dx.doi.org/10.1016/j.clinbiochem.2012.01.012] [PMID: 22285385]
[24]
Zhang, R.; Zhu, H.; Ding, L.; Yang, Z. Determination of asperosaponin VI and its active metabolite hederagenin in rat tissues by LC–MS/MS: Application to a tissue distribution study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2014, 959, 22-26.
[http://dx.doi.org/10.1016/j.jchromb.2014.03.030] [PMID: 24747520]
[25]
Wang, P.; Sun, J.; Xu, J.; Yan, Q.; Gao, E.; Qu, W.; Zhao, Y.; Yu, Z. Pharmacokinetics, tissue distribution and excretion study of dictamnine, a major bioactive component from the root bark of Dictamnus dasycarpus Turcz. (Rutaceae). J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2013, 942-943, 1-8.
[http://dx.doi.org/10.1016/j.jchromb.2013.10.025] [PMID: 24200865]
[26]
Obermeier, B.; Daneman, R.; Ransohoff, R.M. Development, maintenance and disruption of the blood-brain barrier. Nat. Med., 2013, 19(12), 1584-1596.
[http://dx.doi.org/10.1038/nm.3407] [PMID: 24309662]
[27]
Chodobski, A.; Zink, B.J.; Szmydynger-Chodobska, J. Blood-brain barrier pathophysiology in traumatic brain injury. Transl. Stroke Res., 2011, 2(4), 492-516.
[http://dx.doi.org/10.1007/s12975-011-0125-x] [PMID: 22299022]

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