目的：研究芒柄花素灌胃给药后在小鼠体内的药动学及其在脑组织中的分布。方法：ICR小鼠灌胃给药芒柄花素（50 mg/kg）后以高效液相色谱法测定其血清及脑组织中的浓度（含量）计算其药动学参数。色谱条件为：AQ C18色谱柱（250 mm×4.6 mm,5 μm）;流动相为：乙腈-0.1%醋酸（55∶45, v/v）。流速为1 mL·min-1;柱温为32℃;检测波长为248 nm。结果：药动学数据与带时滞的二室模型最为匹配。雄、雌小鼠血清中分布半衰期分别为16.10 min、15.72 min, 消除半衰期分别为395.51 min、384.28 min,达峰浓度分别为893.53 ng/mL、939.64 ng/mL,曲线下面积（AUC）分别为110 070.91 ng/mL·min、112 157.66 ng/mL·min。脑中药物浓度的变化规律与血清中相似,以脑与血清的AUC比值计算平均脑/血浓度比（C脑/C血）, 雄性为1.13,雌性为1.19,表明芒柄花素具有较好的透脑性能且雌性略优于雄性。8 h后在血清及脑组织中几乎检测不到。结论：芒柄花素小鼠口服给予芒柄花素后能迅速透脑,但消降也相对较快,其在雌性小鼠中的透脑能力略强于雄性。
Abstract
Objective To study the pharmacokinetics and distribution of mangiferin in brain tissue of mice after oral administration. Methods ICR mice were orally administered with mangiferin (50 mg/kg), and the concentration (content) in their serum and brain tissue was determined by high-performance liquid chromatography to calculate their pharmacokinetic parameters. The chromatographic conditions are: AQ C18 column (250mm×4.6mm, 5 μm); The mobile phase is acetonitrile 0.1% acetic acid (55∶45, v/v). The flow rate is 1 mL·min-1; The column temperature is 32℃; The detection wavelength is 248 nm. Results The pharmacokinetic data fit best matched the two -chambers model with time delay. The distribution half-life in the serum of male and female mice is 16.10 min, 15.72 min respectively, the elimination half-life is 395.51 min, 384.28 min, the peak concentrations are 893.53 ng/mL, 939.64 ng/mL, and the area under the curve (AUC) is 110 070.91 ng/mL·min, 112 157.66 ng/mL·min, respectively. The variation profile of drug concentration in the brain is similar to that in serum. The average brain/blood concentration ratio (CBrain/CBlood) is calculated based on the AUC ratio of the brain to serum, with a value of 1.13 for males and 1.19 for females, indicating that formononetin has good brain permeability both in male and females and the latter are slightly better than the former. It is almost undetectable in serum and brain tissue 8 hours after dosing. Conclusion Fomononetin can rapidly penetrate the brain after oral administration to mice, but the attenuation is also relatively fast. The brain penetration ability of formononetin is slightly stronger in female mice than in males.
关键词
芒柄花素 /
脑 /
高效液相色谱
Key words
formononetin /
brain /
high performance liquid chromatography
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参考文献
[1] 白月, 王红芳, 黄怀鹏. 芒柄花素药理作用的研究进展[J]. 现代药物与临床, 2022, 37(2): 425-432.
[2] 丛亚婷, 翁宗琴, 张子昕, 等. 芒柄花素抗肿瘤的研究进展[J/OL]. 中药药理与临床, 1-14[2025-02-21].https://doi.org/10.13412/j.cnki.zyyl.20240912.002.
[3] DUTRA J M, ESPITIA P J P, BATISTA R A . Formononetin: Biological Effects and Uses - A review[J]. Food Chemistry, 2021, 359(5): 129975.
[4] 田亚静, 杨雪, 汪静, 等. 芒柄花素对妊娠期糖尿病大鼠氧化应激损伤的影响[J]. 天津医药, 2023, 51(7): 734-739.
[5] 林海, 易金容, 饶运帷. 芒柄花素对脂多糖诱导的肺泡上皮细胞凋亡及炎症反应的抑制作用[J]. 中国药房, 2023, 34(22): 2721-2726.
[6] 邹小蓉, 徐露. 刺芒柄花素对脑缺血再灌注损伤大鼠的保护作用及其机制研究[J]. 中国现代应用药学, 2018, 35(6): 855-858.
[7] 刘其羽, 邹一峰, 黎阳. 葛根中刺芒柄花素预防和改善阿尔兹海默病的机制[J]. 武汉轻工大学学报, 2024, 43(4): 23-32+48.
[8] 黄渊智, 刘红玲. 芒柄花素通过miR-1229/ZDHHC9分子轴对胶质瘤细胞增殖、活力及凋亡的影响[J]. 世界中医药, 2024, 19(3): 329-335+341.
[9] 张星, 陆兔林, 毛春芹, 等. 不同器具煎煮补阳还五汤的4种成分含量比较[J]. 中国医院药学杂志, 2013, 33(7): 533-536.
[10] 陈惠军, 刁秀敏, 冯黎明. 补阳还五汤加味(水蛭与鸡血藤)联合丹参川芎嗪治疗急性脑梗死的疗效及对凝血因子和血液黏度影响的临床研究[J]. 世界最新医学信息文摘, 2019, 19(26): 174-175.
[11] 李嘉雨. 天然冰片促进芒柄花素透过血脑屏障发挥抗脑缺血作用的研究[D]. 福州: 福建中医药大学, 2022.
[12] LIU Z, ZHENG X, LV J, et al.Pharmacokinetic synergy from the taxane extract of Taxus chinensis improves the bioavailability of paclitaxel[J]. Phytomedicine, 2015, 22(3): 573-578.
[13] ZHANG Y, HUO M, ZHOU J, et al.PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel[J]. Comput Methods Programs Biomed, 2010, 99(3): 306-314.
[14] DI L, KERNS EH, CARTER GT.Strategies to assess blood-brain barrier penetration[J]. Expert Opin Drug Discov, 2008, 3(6): 677-687.
[15] WANG YH, GAO XH, LI X, et al.Design, synthesis and the evaluation of cholinesterase inhibition and blood-brain permeability of daidzein derivatives or analogs[J]. Chem Biol Drug Des, 2023, 102(4): 718-729.
基金
广东省中医药局科研项目“补阳还五汤控DHEA治疗脑梗死恢复期认知功障碍的机制研究”（20221414）; 李轩东莞市名中医工作室建设项目（东卫函2021【134】号）
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