黄芩不同炮制品黄酮类成分的整合药动学研究
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国家自然科学基金项目(82173979,81173553)——黄芩栀子炮制配伍增强“宁肺火”、“止血热”科学内涵研究,基于黄芩清肺汤的黄芩、栀子饮片“炮制配伍”示范性研究;道地药材国家重点实验室培育基地自主选题;国家中医药管理局中药炮制技术传承基地项目(国中医药科技中药〔2022〕59号)


Integrated Pharmacokinetics of Flavonoids from Different Processed Products of Scutellariae Radix
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    摘要:

    目的:比较黄芩炮制品中8种黄酮类成分在大鼠体内含量的差异,探明黄芩不同炮制品的药动学行为的差异,为其炮制原理的阐明提供科学依据。方法:选取20只SD大鼠随机分为空白组、生黄芩、酒黄芩和黄芩炭4组,每组5只,灌胃给药。以山柰素为内标,采用超高效液相色谱-三重四级杆串联质谱法(UPLC-QQQ-MS/MS)测定不同时间点大鼠血清中黄芩苷、5,7,2',5'-四羟基-8,6'-二甲氧基黄酮(HQ-6)、汉黄芩苷、黄芩素、汉黄芩素、白杨素、5,6-二羟基-7,8,2',6'-四甲氧基黄酮(HQ-2)、千层纸素-A等的浓度,利用各成分药-时曲线下面积(AUC0→∞)百分比作为自定义权重系数,计算在大鼠体内的综合血药浓度并建立整合药物代谢动力学(药动学)模型,比较黄芩炮制品中黄酮类成分的整合药动学参数的差异。结果:单成分的AUC0→∞差异较大;多成分整合药动力学结果显示,黄芩酒炙后,8种黄酮类成分的滞留时间(MRT0→∞)由17.22 h缩短为13.13 h。首次达峰时间(Tmax)由0.50 h缩短为0.25 h,2次(Tmax由4 h延长为8 h。黄芩炒炭后,黄芩炭的多成分整体的MRT0→∞为10.07 h,与酒黄芩比较,差异无统计学意义(P>0.05)。黄芩炭存在0.25、1、2 h,3次达峰。结论:该方法专属性强、灵敏度高,可作为大鼠血清中8种黄酮类成分的同步检测及其药动学研究的方法,进一步诠释了黄芩“酒炙增效,炒炭存性”的科学内涵。

    Abstract:

    To compare the content differences of eight flavonoid components in different processed products of Scutellariae Radix(SR) in rats and to explore the differences of pharmacokinetic behaviors of these products,providing scientific evidence for elucidating the processing principles.Methods:Twenty SD rats were randomly divided into control group,raw SR group,wine-processed SR group,and carbonized SR group,with five rats in each group.Drugs were administered by gavage.Using kaempferol as an internal standard,ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-QQQ-MS/MS) was employed to measure the concentrations of baicalin,5,7,2',5'-tetrahydroxy-8,6'-dimethoxyflavone(HQ-6),wogonoside,baicalein,wogonin,chrysin,5,6-dihydroxy-7,8,2',6'-tetramethoxyflavone(HQ-2),and oroxylin A in rat serum at various time points.The area under the curve(AUC0→∞) percentage of each component was used as a custom weighting coefficient to calculate the overall serum concentration of the drugs in rats and establish an integrated pharmacokinetic model to compare the differences in pharmacokinetic parameters of flavonoid components in processed products of SR.Results:The AUC0→∞ for single components varied significantly.The integrated pharmacokinetic results of multiple components showed that after wine processing of SR,the mean retention time(MRT0→∞) of the eight flavonoid components was reduced from 17.22 h to 13.13 h.The time to reach peak concentration(Tmax) decreased from 0.50 h to 0.25 h,while the time to secondary peak increased from 4 h to 8 h.After carbonization of SR,the overall MRT for the carbonized product was 10.07 h,which was not significantly different from the wine-processed product(P>0.05).The carbonized SR showed three peaks at 0.25,1,and 2 h.Conclusion:This method is specific and highly sensitive,suitable for simultaneous detection and pharmacokinetic studies of eight flavonoid components in rat serum,further elucidating the scientific meaning of “enhanced efficacy by wine processing and stability by carbonization' for SR.

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宋亚南,王云,陈影,黄琪,张村.黄芩不同炮制品黄酮类成分的整合药动学研究[J].世界中医药,2024,(17).

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  • 收稿日期:2023-08-29
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  • 在线发布日期: 2024-10-14
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