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Article(id=1239184761055408806, tenantId=1146029695717560320, journalId=1205117023404326918, issueId=1239184752507408921, articleNumber=null, orderNo=null, doi=10.16155/j.0254-1793.2024-0377, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1717516800000, receivedDateStr=2024-06-05, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773374269974, onlineDateStr=2026-03-13, pubDate=1735574400000, pubDateStr=2024-12-31, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773374269974, onlineIssueDateStr=2026-03-13, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773374269974, creator=13701087609, updateTime=1773374269974, updator=13701087609, issue=Issue{id=1239184752507408921, tenantId=1146029695717560320, journalId=1205117023404326918, year='2024', volume='44', issue='12', pageStart='2011', pageEnd='2188', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1773374267937, creator=13701087609, updateTime=1773374446543, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1239185501702377864, tenantId=1146029695717560320, journalId=1205117023404326918, issueId=1239184752507408921, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1239185501702377865, tenantId=1146029695717560320, journalId=1205117023404326918, issueId=1239184752507408921, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=2011, endPage=2022, ext={EN=ArticleExt(id=1239184763018343095, articleId=1239184761055408806, tenantId=1146029695717560320, journalId=1205117023404326918, language=EN, title=Comparative pharmacokinetic characterization of multi-components in different artifacts of Ligustri Lucidi Fructus based on UPLC-Orbitrap MS/MS*, columnId=1239184757519602223, journalTitle=Chinese Journal of Pharmaceutical Analysis, columnName=Metabolism Analysis, runingTitle=null, highlight=null, articleAbstract=
Objective:

To establish an UPLC-MS method for the analysis of salidroside, methyloleoside, specnuezhenide, acteoside, oleuropein, and G13 in plasma, and the differences in pharmacokinetic profiles of five different concoctions of Ligustri Lucidi Fructus, wine Ligustri Lucidi Fructus, vinegar Ligustri Lucidi Fructus, salt Ligustri Lucidi Fructus and steamed Ligustri Lucidi Fructus in vivo of rats were investigated.

Methods:

SPF-grade male SD rats were randomly divided into 6 groups, and were given 4.2 g·kg-1 of aqueous extracts of different concoctions of Ligustri Lucidi Fructus by gavage (for the amount of raw drug), and the plasma samples were methanol-precipitated proteins with geniposide as the internal standard, and the plasma samples were used to determine salidroside, methyloleoside, specnuezhenide, acteoside, oleuropein, and G13 in the plasma of the rats in the different time points by using the negative-ion SIM mode of UPLC-MS/MS. Kinetica 5.1 software was used to calculate the pharmacokinetic parameters, and GraphPad Prism 8.4.0 software was used to analyze the data.

Results:

The mass concentrations of salidroside, methyloleoside, specnuezhenide, acteoside and oleuropein were in the range of 2.00-1 385 ng·mL-1, and the mass concentration of G13 was in the range of 1.30-650 ng·mL-1, with good linearity, the relative standard deviations of the precision were all less than 10%, the recoveries of the extracts were all in the range of 85%-105%, and the matrix effect and stability were in accordance with the requirements of biological samples. The results of pharmacokinetic study showed that the AUC0-∞, MRT0-t, t1/2, and Cmax of acteoside were significantly higher in wine Ligustri Lucidi Fructus (P<0.01) compared to raw Ligustri Lucidi Fructus, which was 751.36 ng·mL-1·h, 5.87 h, 377.82 h, and 38.11 ng·mL-1, respectively. Cmax, AUC0-∞, and t1/2 were significantly higher (P<0.01) for specnuezhenide and G13 in salt Ligustri Lucidi Fructus compared to raw Ligustri Lucidi Fructus, with Cmax of specnuezhenide and G13 in salt Ligustri Lucidi Fructus were 66.45 ng·mL-1 and 204.27 ng·mL-1, respectively. The AUC0-∞ were 342.69 ng·mL-1 and 423.44 ng·mL-1·h, and t1/2 were 101.64 h and 15.98 h, respectively. Compared to raw Ligustri Lucidi Fructus, the Cmax of oleuropein was significantly higher (P<0.05) in vinegar Ligustri Lucidi Fructus, wine Ligustri Lucidi Fructus, and steamed Ligustri Lucidi Fructus with 66.81 ng·mL-1, 68.00 ng·mL-1, and 66.38 ng·mL-1, respectively. The AUC0-∞ of salidroside and methyloleoside was the highest in vinegar Ligustri Lucidi Fructus, which was 5 782.74 ng·mL-1 and 545.26 ng·mL-1·h, respectively.

Conclusion:

This study reveals the changing law of the six active ingredients in different artillery products of Ligustri Lucidi Fructus in vivo and their different characteristics, which provides a basis for the clinical application of different artillery products of Ligustri Lucidi Fructus.

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目的：

建立血浆中红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13的超高效液相色谱-质谱分析方法，探究女贞子、酒女贞子、醋女贞子、盐女贞子、清蒸女贞子5种不同炮制品在大鼠体内的药代动力学特征差异。

方法：

SPF级雄性SD大鼠随机分为6组，分别灌胃给予女贞子不同炮制品水提液4.2 g·kg-1（以生药量计），以京尼平苷为内标物，血浆样品经甲醇沉淀蛋白，采用UPLC-MS/MS负离子SIM模式测定不同时间点大鼠血浆中红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷以及女贞苷G13的浓度，Kinetica 5.1软件计算药代动力学参数，GraphPad Prism 8.4.0软件进行数据分析。

结果：

红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷质量浓度在2.00~1 385 ng·mL-1范围内，女贞苷G13质量浓度在1.30~650 ng·mL-1范围内线性关系良好，精密度RSD均<10%，提取回收率均在85%~105%，基质效应和稳定性均符合生物样品的要求。药动学研究结果显示，与生女贞子相比，酒女贞子的毛蕊花糖苷AUC0-∞、MRT0-t、t1/2、Cmax均显著升高（P<0.01），分别为751.36 ng·mL-1·h，5.87 h，377.82 h，38.11 ng·mL-1；盐女贞子的特女贞苷和女贞苷G13 Cmax、AUC0-∞和t1/2均显著升高（P<0.01），Cmax分别为66.45、204.27 ng·mL-1，AUC0-∞分别为342.69、423.44 ng·mL-1·h，t1/2分别为101.64、15.98 h；醋蒸、酒蒸、清蒸女贞子的橄榄苦苷Cmax显著升高（P<0.05），分别为66.81、68.00、66.38 ng·mL-1。醋女贞子的红景天苷和木樨榄苷-11-甲酯AUC0-∞最高，分别为5 782.74、545.26 ng·mL-1·h。

结论：

本研究揭示了女贞子不同炮制品中6个活性成分在体内的变化规律及其差异特点，为女贞子不同炮制品的临床应用提供依据。

, correspAuthors=冯素香, authorNote=null, correspAuthorsNote=
**Tel：13526403080；E-mail：
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Research statue on pharmacological action of Oleuropein[J]. Chin J Clin Pharmacol，2019，35(24)：3265, articleTitle=Research statue on pharmacological action of Oleuropein, refAbstract=null)], funds=[Fund(id=1239218782955163993, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, awardId=No.82374041, language=CN, fundingSource=*国家自然科学基金项目(No.82374041), fundOrder=null, country=null), Fund(id=1239218783080993118, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, awardId=2023ZY1029, language=CN, fundingSource=河南省中医药科学研究专项课题(2023ZY1029), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1239218769537585969, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, xref=1., ext=[AuthorCompanyExt(id=1239218769545974578, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, companyId=1239218769537585969, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Henan University of Chinese Medicine, Zhengzhou 450046, China), AuthorCompanyExt(id=1239218769550168883, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, companyId=1239218769537585969, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.河南中医药大学，郑州 450046)]), AuthorCompany(id=1239218769726329655, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, xref=2., ext=[AuthorCompanyExt(id=1239218769768272698, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, companyId=1239218769726329655, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province & Education Ministry of P.R., Zhengzhou 450046, China), AuthorCompanyExt(id=1239218769793438524, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, companyId=1239218769726329655, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.呼吸疾病中医药防治省部共建协同创新中心，郑州 450046)]), AuthorCompany(id=1239218771315970884, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, xref=3., ext=[AuthorCompanyExt(id=1239218771324359493, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, companyId=1239218771315970884, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.Henan Engineering Research Center of Modern Chinese Medicine Research, Development and application, Zhengzhou 450046, China), AuthorCompanyExt(id=1239218771332748102, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, companyId=1239218771315970884, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.河南省现代中药研发与应用工程研究中心，郑州 450046)])], figs=[ArticleFig(id=1239218777963942069, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Fig.1, caption=Chromatograms of each component to be measured in rat plasma, figureFileSmall=Pz8EIVMVhmSUeZ+Nd/JIeg==, figureFileBig=gyH3wr6hGSAHu5vTHl0LtQ==, tableContent=null), ArticleFig(id=1239218778165268667, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=图1, caption=大鼠血浆中各待测成分色谱图

a.空白血浆加对照品(blank plasma with reference substance)　b.给药后大鼠血浆（rat plasma after administration）　c.空白血浆（blank plasma ）

, figureFileSmall=Pz8EIVMVhmSUeZ+Nd/JIeg==, figureFileBig=gyH3wr6hGSAHu5vTHl0LtQ==, tableContent=null), ArticleFig(id=1239218778270126272, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Fig.2, caption=Mean blood concentration-time curve of salidroside in rats after gavage of extracts of different concoctions of Ligustri Lucidi Fructus, figureFileSmall=0Hp9lDvzFTie+w+c+h1CiQ==, figureFileBig=3vdKTKAjbd013kn1/fdr3g==, tableContent=null), ArticleFig(id=1239218778349818053, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=图2, caption=大鼠灌胃女贞子不同炮制品提取液后红景天苷平均血药浓度-时间曲线, figureFileSmall=0Hp9lDvzFTie+w+c+h1CiQ==, figureFileBig=3vdKTKAjbd013kn1/fdr3g==, tableContent=null), ArticleFig(id=1239218778458869960, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Fig.3, caption=Mean blood concentration-time curve of methyloleoside in rats after gavage of extracts of different concoctions of Ligustri Lucidi Fructus, figureFileSmall=42vb33ZB93xCoezvCvaemg==, figureFileBig=WoVCEWcYOEKER0ZrDCYcNw==, tableContent=null), ArticleFig(id=1239218778572116174, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=图3, caption=大鼠灌胃女贞子不同炮制品提取液后木樨榄苷-11-甲酯平均血药浓度-时间曲线, figureFileSmall=42vb33ZB93xCoezvCvaemg==, figureFileBig=WoVCEWcYOEKER0ZrDCYcNw==, tableContent=null), ArticleFig(id=1239218778697945300, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Fig.4, caption=Mean blood concentration-time curve of specnuezhenide in rats after gavage of extracts of different concoctions of Ligustri Lucidi Fructus, figureFileSmall=OakHhkksjY26Qm0AjCbEBQ==, figureFileBig=0t/ZQsGcOJ3MlslafK4OSA==, tableContent=null), ArticleFig(id=1239218778827968732, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=图4, caption=大鼠灌胃女贞子不同炮制品提取液后特女贞苷平均血药浓度-时间曲线, figureFileSmall=OakHhkksjY26Qm0AjCbEBQ==, figureFileBig=0t/ZQsGcOJ3MlslafK4OSA==, tableContent=null), ArticleFig(id=1239218779947847905, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Fig.5, caption=Mean blood concentration-time curve of acteoside in rats after gavage of extracts of different concoctions of Ligustri Lucidi Fructus, figureFileSmall=bEgRibGgrb7GL7Ugy6o+og==, figureFileBig=aN3kN428y6a/kiV4Cr+qzg==, tableContent=null), ArticleFig(id=1239218780094648550, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=图5, caption=大鼠灌胃女贞子不同炮制品提取液后毛蕊花糖苷平均血药浓度-时间曲线, figureFileSmall=bEgRibGgrb7GL7Ugy6o+og==, figureFileBig=aN3kN428y6a/kiV4Cr+qzg==, tableContent=null), ArticleFig(id=1239218780207894761, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Fig.6, caption=Mean blood concentration-time curve of oleuropein in rats after gavage of extracts of different concoctions of Ligustri Lucidi Fructus, figureFileSmall=UDFy2tIDeZdEOEDuTWo/OQ==, figureFileBig=HuyLc9SElVi//2EjtQ4SvQ==, tableContent=null), ArticleFig(id=1239218780325335278, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=图6, caption=大鼠灌胃女贞子不同炮制品提取液后橄榄苦苷平均血药浓度-时间曲线, figureFileSmall=UDFy2tIDeZdEOEDuTWo/OQ==, figureFileBig=HuyLc9SElVi//2EjtQ4SvQ==, tableContent=null), ArticleFig(id=1239218780434387184, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Fig.7, caption=Mean blood concentration-time curve of G13 in rats after gavage of extracts of different concoctions of Ligustri Lucidi Fructus, figureFileSmall=CwPi9/gA0hIgaDYKLjhYHw==, figureFileBig=lfmaRifSCUAwkNfD0FunYA==, tableContent=null), ArticleFig(id=1239218780535050483, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=图7, caption=大鼠灌胃女贞子不同炮制品提取液后女贞苷G13平均血药浓度-时间曲线, figureFileSmall=CwPi9/gA0hIgaDYKLjhYHw==, figureFileBig=lfmaRifSCUAwkNfD0FunYA==, tableContent=null), ArticleFig(id=1239218780618936568, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Tab.1, caption=

Regression equation，correlation coefficient (r)，linear range，limit of detection and limit of quantification of the component to be measured

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		回归方程
(regression equation)		定量范围
(quantitative range)/（ng·mL-1）		 rLOD/（ng·mL-1）LOQ/（ng·mL-1）
红景天苷(salidroside) Y=3.992×10-4X+4.100×10-32.101~1 0500.998 70.630 32.101
木樨榄苷-11-甲酯(methyloleoside) Y=1.314×10-3X-6.300×10-32.001~1 0000.999 00.600 32.001
特女贞苷(specnuezhenide) Y=2.641×10-3X+8.860×10-22.019~1 0100.998 70.605 72.019
毛蕊花糖苷(acteoside) Y=9.334×10-4X+7.130×10-22.770~1 3850.995 30.831 02.770
橄榄苦苷(oleuropein) Y=2.942×10-3X+7.470×10-22.440~1 2200.998 00.732 02.440
女贞苷G13(G13) Y=1.010×10-4X+4.400×10-31.300~650.10.998 50.390 01.300
), ArticleFig(id=1239218780757348604, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=表1, caption=

待测成分的回归方程、相关系数（r）、线性范围、检测限（LOD）、定量限（LOQ）

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		回归方程
(regression equation)		定量范围
(quantitative range)/（ng·mL-1）		 rLOD/（ng·mL-1）LOQ/（ng·mL-1）
红景天苷(salidroside) Y=3.992×10-4X+4.100×10-32.101~1 0500.998 70.630 32.101
木樨榄苷-11-甲酯(methyloleoside) Y=1.314×10-3X-6.300×10-32.001~1 0000.999 00.600 32.001
特女贞苷(specnuezhenide) Y=2.641×10-3X+8.860×10-22.019~1 0100.998 70.605 72.019
毛蕊花糖苷(acteoside) Y=9.334×10-4X+7.130×10-22.770~1 3850.995 30.831 02.770
橄榄苦苷(oleuropein) Y=2.942×10-3X+7.470×10-22.440~1 2200.998 00.732 02.440
女贞苷G13(G13) Y=1.010×10-4X+4.400×10-31.300~650.10.998 50.390 01.300
), ArticleFig(id=1239218780887372033, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Tab.2, caption=

Extraction recovery and matrix effect of the characteristic components of different concoctions of Ligustri Lucidi Fructus

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		浓度
(concentration)/（ng·mL-1）		基质效应(matrix effect)提取回收率(extraction recovery)
（mean ± SD）/%RSD/%（mean ± SD）/%RSD/%
红景天苷(salidroside)525.294.4±2.62.897.7±2.42.5
42.02100.8±1.81.893.4±2.62.8
4.20298.0±1.21.298.10±2.2192.3
木樨榄苷-11-甲酯(methyloleoside)500.395.1±2.93.095.98±3.0713.2
40.0293.6±2.02.196.45±2.8322.9
4.00299.1±2.02.0100.1±1.6371.6
特女贞苷(specnuezhenide)504.898.2±1.91.987.13±2.1822.5
40.3996.3±1.71.794.93±2.6152.8
4.03995.8±3.13.393.16±2.4662.6
毛蕊花糖苷(acteoside)692.699.8±3.03.097.86±4.0324.1
55.4199.5±3.03.195.64±3.7073.9
5.541100.8±2.62.6100.2±2.92.9
橄榄苦苷(oleuropein)610.198.7±3.33.398.3±3.33.4
48.80102.3±3.73.799.2±3.43.5
4.880102.2±3.53.496.0±3.03.1
女贞苷G13(G13)325.096.7±3.53.798.2±2.02.0
26.0092.6±1.92.098.8±2.93.0
2.60099.9±2.22.293.3±3.33.6
), ArticleFig(id=1239218781000618243, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=表2, caption=

女贞子不同炮制品特征成分的提取回收率和基质效应

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		浓度
(concentration)/（ng·mL-1）		基质效应(matrix effect)提取回收率(extraction recovery)
（mean ± SD）/%RSD/%（mean ± SD）/%RSD/%
红景天苷(salidroside)525.294.4±2.62.897.7±2.42.5
42.02100.8±1.81.893.4±2.62.8
4.20298.0±1.21.298.10±2.2192.3
木樨榄苷-11-甲酯(methyloleoside)500.395.1±2.93.095.98±3.0713.2
40.0293.6±2.02.196.45±2.8322.9
4.00299.1±2.02.0100.1±1.6371.6
特女贞苷(specnuezhenide)504.898.2±1.91.987.13±2.1822.5
40.3996.3±1.71.794.93±2.6152.8
4.03995.8±3.13.393.16±2.4662.6
毛蕊花糖苷(acteoside)692.699.8±3.03.097.86±4.0324.1
55.4199.5±3.03.195.64±3.7073.9
5.541100.8±2.62.6100.2±2.92.9
橄榄苦苷(oleuropein)610.198.7±3.33.398.3±3.33.4
48.80102.3±3.73.799.2±3.43.5
4.880102.2±3.53.496.0±3.03.1
女贞苷G13(G13)325.096.7±3.53.798.2±2.02.0
26.0092.6±1.92.098.8±2.93.0
2.60099.9±2.22.293.3±3.33.6
), ArticleFig(id=1239218781101281544, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Tab.3, caption=

Stability of the characteristic components of different concoctions of Ligustri Lucidi Fructus under different conditions

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		浓度
(concentration)/（ng·mL-1）		短期稳定性
(short-term stability)		冻融稳定性
(freeze-thaw stability)		长期稳定性
(long-term stability)
测得量
(detected) mean ± SD/（ng·mL-1）		RSD/%测得量
(detected) mean ± SD/（ng·mL-1）		RSD/%测得量
(detected) mean ± SD/（ng·mL-1）		RSD/%
红景天苷(salidroside)525.2518.1±7.9801.5514.6±17.283.4527.4±0.722 60.13
42.0240.87±1.4863.642.16±1.3243.142.48±1.3713.2
4.2024.158±0.093 402.24.316±0.092 352.14.152±0.075 361.8
木樨榄苷-11-甲酯(methyloleoside)500.3497.1±14.072.8510.0±6.0791.2503.7±9.6301.9
40.0242.07±1.4913.540.52±0.434 31.141.20±2.8226.8
4.0024.184±0.358 08.64.050±0.052 331.34.000±0.052 681.3
特女贞苷(specnuezhenide)504.8505.8±7.1211.4508.8±6.4201.3500.9±4.1670.83
40.3941.00±1.9294.740.92±0.508 61.241.64±0.636 71.5
4.0394.027±0.112 22.84.063±0.087 752.24.027±0.054 161.3
毛蕊花糖苷(acteoside)692.6691.7±2.8720.41671.0±20.903.1667.7±9.8581.5
55.4152.46±2.2084.254.46±0.477 10.8855.50±0.848 91.5
5.5415.523±0.250 64.55.315±0.113 82.15.386±0.112 82.1
橄榄苦苷(oleuropein)610.1614.1±7.7901.3609.4±6.8751.1608.6±3.1900.52
48.8047.68±0.665 41.448.51±3.1496.547.14±1.1482.4
4.8804.686±0.138 53.04.610±0.270 05.94.768±0.155 53.3
女贞苷G13(G13)325.0324.6±19.265.9322.5±23.617.3318.1±21.556.8
26.0025.45±0.747 32.927.13±0.422 71.626.21±1.5696.0
2.6002.687±0.117 24.42.449±0.124 55.12.545±0.064 722.5
), ArticleFig(id=1239218781218722062, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=表3, caption=

女贞子不同炮制品特征成分在不同条件下的稳定性

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		浓度
(concentration)/（ng·mL-1）		短期稳定性
(short-term stability)		冻融稳定性
(freeze-thaw stability)		长期稳定性
(long-term stability)
测得量
(detected) mean ± SD/（ng·mL-1）		RSD/%测得量
(detected) mean ± SD/（ng·mL-1）		RSD/%测得量
(detected) mean ± SD/（ng·mL-1）		RSD/%
红景天苷(salidroside)525.2518.1±7.9801.5514.6±17.283.4527.4±0.722 60.13
42.0240.87±1.4863.642.16±1.3243.142.48±1.3713.2
4.2024.158±0.093 402.24.316±0.092 352.14.152±0.075 361.8
木樨榄苷-11-甲酯(methyloleoside)500.3497.1±14.072.8510.0±6.0791.2503.7±9.6301.9
40.0242.07±1.4913.540.52±0.434 31.141.20±2.8226.8
4.0024.184±0.358 08.64.050±0.052 331.34.000±0.052 681.3
特女贞苷(specnuezhenide)504.8505.8±7.1211.4508.8±6.4201.3500.9±4.1670.83
40.3941.00±1.9294.740.92±0.508 61.241.64±0.636 71.5
4.0394.027±0.112 22.84.063±0.087 752.24.027±0.054 161.3
毛蕊花糖苷(acteoside)692.6691.7±2.8720.41671.0±20.903.1667.7±9.8581.5
55.4152.46±2.2084.254.46±0.477 10.8855.50±0.848 91.5
5.5415.523±0.250 64.55.315±0.113 82.15.386±0.112 82.1
橄榄苦苷(oleuropein)610.1614.1±7.7901.3609.4±6.8751.1608.6±3.1900.52
48.8047.68±0.665 41.448.51±3.1496.547.14±1.1482.4
4.8804.686±0.138 53.04.610±0.270 05.94.768±0.155 53.3
女贞苷G13(G13)325.0324.6±19.265.9322.5±23.617.3318.1±21.556.8
26.0025.45±0.747 32.927.13±0.422 71.626.21±1.5696.0
2.6002.687±0.117 24.42.449±0.124 55.12.545±0.064 722.5
), ArticleFig(id=1239218781310996751, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Tab.4, caption=

Pharmacogenetic parameters of salidroside in rats after gavage of extracts of different concoctions of Ligustri Lucidi Fructus

, figureFileSmall=null, figureFileBig=null, tableContent=
名称
（designation）		AUC0-t/（ng·mL-1·h）AUC0-∞/（ng·mL-1·h）MRT0-t/h t1/2/h Tmax/hCLz/F/（L·h-1） Cmax/（ng·mL-1）
女贞子(Ligustri Lucidi Fructus)4 219.87±227.284 228.33±228.743.48±0.053.02±0.070.75±0.00277.38±15.011 091.02±45.96
醋蒸女贞子(vinegar Ligustri Lucidi Fructus)5 772.03±458.95b5 782.74±463.41b3.55±0.103.14±0.220.83±0.12237.15±16.811 350.57±92.60b
酒蒸女贞子(wine Ligustri Lucidi Fructus)4 213.89±413.99d4 218.15±415.30d3.36±0.232.59±0.11bd0.83±0.12315.95±30.84d1 340.72±154.64b
盐蒸女贞子(salt Ligustri Lucidi Fructus)4 079.34±482.26f4 086.49±485.08df3.29±0.202.40±0.11bd0.79±0.09333.41±38.40d1 216.44±72.25
清蒸女贞子(steamed Ligustri Lucidi Fructus)4 593.34±640.73cf4 601.14±643.42cf3.50±0.272.68±0.19adg0.83±0.12302.87±42.49c1 435.10±26.54bh
), ArticleFig(id=1239218781407465747, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=表4, caption=

大鼠灌胃女贞子不同炮制品提取液后红景天苷药代参数

, figureFileSmall=null, figureFileBig=null, tableContent=
名称
（designation）		AUC0-t/（ng·mL-1·h）AUC0-∞/（ng·mL-1·h）MRT0-t/h t1/2/h Tmax/hCLz/F/（L·h-1） Cmax/（ng·mL-1）
女贞子(Ligustri Lucidi Fructus)4 219.87±227.284 228.33±228.743.48±0.053.02±0.070.75±0.00277.38±15.011 091.02±45.96
醋蒸女贞子(vinegar Ligustri Lucidi Fructus)5 772.03±458.95b5 782.74±463.41b3.55±0.103.14±0.220.83±0.12237.15±16.811 350.57±92.60b
酒蒸女贞子(wine Ligustri Lucidi Fructus)4 213.89±413.99d4 218.15±415.30d3.36±0.232.59±0.11bd0.83±0.12315.95±30.84d1 340.72±154.64b
盐蒸女贞子(salt Ligustri Lucidi Fructus)4 079.34±482.26f4 086.49±485.08df3.29±0.202.40±0.11bd0.79±0.09333.41±38.40d1 216.44±72.25
清蒸女贞子(steamed Ligustri Lucidi Fructus)4 593.34±640.73cf4 601.14±643.42cf3.50±0.272.68±0.19adg0.83±0.12302.87±42.49c1 435.10±26.54bh
), ArticleFig(id=1239218781558460699, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Tab.5, caption=

Pharmacogenetic parameters of methyloleoside in rats after gavage of extracts of different concoctions of Ligustri Lucidi Fructus

, figureFileSmall=null, figureFileBig=null, tableContent=
名称
（designation）		AUC0-t/（ng·mL-1·h）AUC0-∞/（ng·mL-1·h）MRT0-t/h t1/2/h Tmax/hCLz/F/（L·h-1） Cmax/（ng·mL-1）
女贞子(Ligustri Lucidi Fructus)413.83±26.69421.94±29.992.42±0.357.06±0.860.75±0.002 830.62±199.96326.04±14.06
醋蒸女贞子(vinegar Ligustri Lucidi Fructus)540.53±17.40b545.26±19.14b2.65±0.144.89±0.500.79±0.09638.53±22.36b288.46±10.66b
酒蒸女贞子(wine Ligustri Lucidi Fructus)428.58±21.76d439.11±29.28d3.05±0.35a6.32±1.770.71±0.09789.79±52.60b278.53±8.43b
盐蒸女贞子(salt Ligustri Lucidi Fructus)412.85±18.47d417.90±21.88d2.50±0.29e4.74±1.190.75±0.00856.41±44.59bc366.93±11.78bdf
清蒸女贞子(steamed Ligustri Lucidi Fructus)369.51±18.44adfg371.50±19.64adfg2.11±0.22cf4.20±1.55a0.50±0.00bdfh793.94±42.21b269.70±6.90bh
), ArticleFig(id=1239218781675901216, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=表5, caption=

大鼠灌胃女贞子不同炮制品提取液后木樨榄苷-11-甲酯药代参数

, figureFileSmall=null, figureFileBig=null, tableContent=
名称
（designation）		AUC0-t/（ng·mL-1·h）AUC0-∞/（ng·mL-1·h）MRT0-t/h t1/2/h Tmax/hCLz/F/（L·h-1） Cmax/（ng·mL-1）
女贞子(Ligustri Lucidi Fructus)413.83±26.69421.94±29.992.42±0.357.06±0.860.75±0.002 830.62±199.96326.04±14.06
醋蒸女贞子(vinegar Ligustri Lucidi Fructus)540.53±17.40b545.26±19.14b2.65±0.144.89±0.500.79±0.09638.53±22.36b288.46±10.66b
酒蒸女贞子(wine Ligustri Lucidi Fructus)428.58±21.76d439.11±29.28d3.05±0.35a6.32±1.770.71±0.09789.79±52.60b278.53±8.43b
盐蒸女贞子(salt Ligustri Lucidi Fructus)412.85±18.47d417.90±21.88d2.50±0.29e4.74±1.190.75±0.00856.41±44.59bc366.93±11.78bdf
清蒸女贞子(steamed Ligustri Lucidi Fructus)369.51±18.44adfg371.50±19.64adfg2.11±0.22cf4.20±1.55a0.50±0.00bdfh793.94±42.21b269.70±6.90bh
), ArticleFig(id=1239218781797536037, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Tab.6, caption=

Pharmacogenetic parameters of specnuezhenide in rats after gavage of extracts of different concoctions of Ligustri Lucidi Fructus

, figureFileSmall=null, figureFileBig=null, tableContent=
名称
（designation）		AUC0-t/（ng·mL-1·h）AUC0-∞/（ng·mL-1·h）MRT0-t/h t1/2/h Tmax/hCLz/F/（L·h-1） Cmax/（ng·mL-1）
女贞子(Ligustri Lucidi Fructus)103.57±8.94119.80±16.785.08±0.9611.35±4.770.79±0.09109 757.40±17 860.5140.53±3.56
醋蒸女贞子(vinegar Ligustri Lucidi Fructus)127.67±11.68b147.34±32.744.66±0.448.58±8.730.75±0.0083 718.67±14 955.38a72.98±1.69b
酒蒸女贞子(wine Ligustri Lucidi Fructus)118.41±4.75133.86±8.944.48±0.159.80±8.770.75±0.0081 218.03±5 223.05a77.21±1.68b
盐蒸女贞子(salt Ligustri Lucidi Fructus)117.77±9.75342.69±74.95bdf4.86±0.30101.64±35.39bdf0.75±0.0038 924.94±10 469.99bdf66.45±4.14bf
清蒸女贞子(steamed Ligustri Lucidi Fructus)92.24±7.52dfh96.15±6.50h2.66±0.27bdfh3.15±0.20h0.75±0.00114 294.60±7 309.99dfh80.50±5.25bch
), ArticleFig(id=1239218781898199338, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=表6, caption=

大鼠灌胃女贞子不同炮制品提取液后特女贞苷药代参数

, figureFileSmall=null, figureFileBig=null, tableContent=
名称
（designation）		AUC0-t/（ng·mL-1·h）AUC0-∞/（ng·mL-1·h）MRT0-t/h t1/2/h Tmax/hCLz/F/（L·h-1） Cmax/（ng·mL-1）
女贞子(Ligustri Lucidi Fructus)103.57±8.94119.80±16.785.08±0.9611.35±4.770.79±0.09109 757.40±17 860.5140.53±3.56
醋蒸女贞子(vinegar Ligustri Lucidi Fructus)127.67±11.68b147.34±32.744.66±0.448.58±8.730.75±0.0083 718.67±14 955.38a72.98±1.69b
酒蒸女贞子(wine Ligustri Lucidi Fructus)118.41±4.75133.86±8.944.48±0.159.80±8.770.75±0.0081 218.03±5 223.05a77.21±1.68b
盐蒸女贞子(salt Ligustri Lucidi Fructus)117.77±9.75342.69±74.95bdf4.86±0.30101.64±35.39bdf0.75±0.0038 924.94±10 469.99bdf66.45±4.14bf
清蒸女贞子(steamed Ligustri Lucidi Fructus)92.24±7.52dfh96.15±6.50h2.66±0.27bdfh3.15±0.20h0.75±0.00114 294.60±7 309.99dfh80.50±5.25bch
), ArticleFig(id=1239218782036611378, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Tab.7, caption=

Pharmacogenetic parameters of acteoside in rats after gavage of extracts of different concoctions of Ligustri Lucidi Fructus

, figureFileSmall=null, figureFileBig=null, tableContent=
名称
（designation）		AUC0-t//(ng·mL-1·h）AUC0-∞/（ng·mL-1·h）MRT0-t/h t1/2/h Tmax/hCLz/F/（L·h-1） Cmax/（ng·mL-1）
女贞子(Ligustri Lucidi Fructus)77.32±6.9895.87±17.235.13±0.3315.96±4.650.75±0.001 549.14±277.3835.23±1.90
醋蒸女贞子(vinegar Ligustri Lucidi Fructus)73.26±3.95125.59±31.525.80±0.21a32.74±17.000.71±0.093 963.52±1 085.7631.12±0.62b
酒蒸女贞子(wine Ligustri Lucidi Fructus)69.90±5.16751.36±501.36bd5.87±0.30b377.82±266.59bd0.71±0.093 266.75±3 792.2438.11±2.31ad
盐蒸女贞子(salt Ligustri Lucidi Fructus)67.54±6.26158.27±66.50f5.80±0.30a56.63±35.65f0.58±0.245 054.25±2 678.3228.12±1.05bcf
清蒸女贞子(steamed Ligustri Lucidi Fructus)63.01±3.54bc104.78±70.53f5.90±0.35b23.48±35.88f0.58±0.128 951.94±3 015.66bce30.94±0.48bfg
), ArticleFig(id=1239218782141468982, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=表7, caption=

大鼠灌胃女贞子不同炮制品提取液后毛蕊花糖苷药代参数

, figureFileSmall=null, figureFileBig=null, tableContent=
名称
（designation）		AUC0-t//(ng·mL-1·h）AUC0-∞/（ng·mL-1·h）MRT0-t/h t1/2/h Tmax/hCLz/F/（L·h-1） Cmax/（ng·mL-1）
女贞子(Ligustri Lucidi Fructus)77.32±6.9895.87±17.235.13±0.3315.96±4.650.75±0.001 549.14±277.3835.23±1.90
醋蒸女贞子(vinegar Ligustri Lucidi Fructus)73.26±3.95125.59±31.525.80±0.21a32.74±17.000.71±0.093 963.52±1 085.7631.12±0.62b
酒蒸女贞子(wine Ligustri Lucidi Fructus)69.90±5.16751.36±501.36bd5.87±0.30b377.82±266.59bd0.71±0.093 266.75±3 792.2438.11±2.31ad
盐蒸女贞子(salt Ligustri Lucidi Fructus)67.54±6.26158.27±66.50f5.80±0.30a56.63±35.65f0.58±0.245 054.25±2 678.3228.12±1.05bcf
清蒸女贞子(steamed Ligustri Lucidi Fructus)63.01±3.54bc104.78±70.53f5.90±0.35b23.48±35.88f0.58±0.128 951.94±3 015.66bce30.94±0.48bfg
), ArticleFig(id=1239218782237937976, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Tab.8, caption=

Pharmacogenetic parameters of oleuropein in rats after gavage of extracts of different concoctions of Ligustri Lucidi Fructus

, figureFileSmall=null, figureFileBig=null, tableContent=
名称
（designation）		AUC0-t/（ng·mL-1·h）AUC0-∞/（ng·mL-1·h）MRT0-t/h t1/2/h Tmax/hCLz/F/（L·h-1） Cmax/（ng·mL-1）
女贞子(Ligustri Lucidi Fructus)120.66±20.50151.77±22.456.78±0.3311.62±2.050.75±0.0014 993.12±2 192.8856.91±4.04
醋蒸女贞子(vinegar Ligustri Lucidi Fructus)132.73±23.56181.58±50.056.18±0.5416.10±6.010.75±0.0010 794.40±2 760.8466.81±7.09a
酒蒸女贞子(wine Ligustri Lucidi Fructus)133.52±32.59176.26±75.875.83±0.9611.85±7.520.71±0.0914 066.72±5 318.1468.00±6.81a
盐蒸女贞子(salt Ligustri Lucidi Fructus)114.26±18.62155.06±39.535.94±0.6813.39±5.300.75±0.0011 810.79±3 436.5663.98±0.93
清蒸女贞子(steamed Ligustri Lucidi Fructus)145.50±21.84151.38±24.255.11±0.43b5.33±0.55c0.71±0.0913 634.15±2 313.1866.38±2.35a
), ArticleFig(id=1239218782376350015, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=表8, caption=

大鼠灌胃女贞子不同炮制品提取液后橄榄苦苷药代参数

, figureFileSmall=null, figureFileBig=null, tableContent=
名称
（designation）		AUC0-t/（ng·mL-1·h）AUC0-∞/（ng·mL-1·h）MRT0-t/h t1/2/h Tmax/hCLz/F/（L·h-1） Cmax/（ng·mL-1）
女贞子(Ligustri Lucidi Fructus)120.66±20.50151.77±22.456.78±0.3311.62±2.050.75±0.0014 993.12±2 192.8856.91±4.04
醋蒸女贞子(vinegar Ligustri Lucidi Fructus)132.73±23.56181.58±50.056.18±0.5416.10±6.010.75±0.0010 794.40±2 760.8466.81±7.09a
酒蒸女贞子(wine Ligustri Lucidi Fructus)133.52±32.59176.26±75.875.83±0.9611.85±7.520.71±0.0914 066.72±5 318.1468.00±6.81a
盐蒸女贞子(salt Ligustri Lucidi Fructus)114.26±18.62155.06±39.535.94±0.6813.39±5.300.75±0.0011 810.79±3 436.5663.98±0.93
清蒸女贞子(steamed Ligustri Lucidi Fructus)145.50±21.84151.38±24.255.11±0.43b5.33±0.55c0.71±0.0913 634.15±2 313.1866.38±2.35a
), ArticleFig(id=1239218782531539268, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=EN, label=Tab.9, caption=

Pharmacogenetic parameters of G13 in rats after gavage of extracts of different concoctions of Ligustri Lucidi Fructus

, figureFileSmall=null, figureFileBig=null, tableContent=
名称
（designation）		AUC0-t/（ng·mL-1·h）AUC0-∞/（ng·mL-1·h）MRT0-t/h t1/2/h Tmax/hCLz/F/（L·h-1） Cmax/（ng·mL-1）
女贞子(Ligustri Lucidi Fructus)291.28±5.90293.26±6.293.47±0.123.88±0.210.75±0.0012 724.58±269.67186.47±2.44
醋蒸女贞子(vinegar Ligustri Lucidi Fructus)267.10±10.20b322.16±19.524.89±0.20b14.53±1.94b0.50±0.0011 424.58±749.73a130.72±5.68b
酒蒸女贞子(wine Ligustri Lucidi Fructus)220.36±7.88bd226.56±10.34bd2.62±0.36bd3.09±0.30d0.50±0.0011 144.68±513.36b150.24±1.02bd
盐蒸女贞子(salt Ligustri Lucidi Fructus)361.08±11.90bdf423.44±50.51bdf3.86±0.20df15.98±7.47bf0.75±0.008 870.09±958.03bdf204.27±7.93bdf
清蒸女贞子(steamed Ligustri Lucidi Fructus)239.06±6.74bdeh239.08±6.74adh1.63±0.03bdfh1.60±0.01dh0.75±0.0013 038.88±371.86dfh166.42±9.02bdfh
), ArticleFig(id=1239218782678339913, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184761055408806, language=CN, label=表9, caption=

大鼠灌胃女贞子不同炮制品提取液后女贞苷G13药代参数

, figureFileSmall=null, figureFileBig=null, tableContent=
名称
（designation）		AUC0-t/（ng·mL-1·h）AUC0-∞/（ng·mL-1·h）MRT0-t/h t1/2/h Tmax/hCLz/F/（L·h-1） Cmax/（ng·mL-1）
女贞子(Ligustri Lucidi Fructus)291.28±5.90293.26±6.293.47±0.123.88±0.210.75±0.0012 724.58±269.67186.47±2.44
醋蒸女贞子(vinegar Ligustri Lucidi Fructus)267.10±10.20b322.16±19.524.89±0.20b14.53±1.94b0.50±0.0011 424.58±749.73a130.72±5.68b
酒蒸女贞子(wine Ligustri Lucidi Fructus)220.36±7.88bd226.56±10.34bd2.62±0.36bd3.09±0.30d0.50±0.0011 144.68±513.36b150.24±1.02bd
盐蒸女贞子(salt Ligustri Lucidi Fructus)361.08±11.90bdf423.44±50.51bdf3.86±0.20df15.98±7.47bf0.75±0.008 870.09±958.03bdf204.27±7.93bdf
清蒸女贞子(steamed Ligustri Lucidi Fructus)239.06±6.74bdeh239.08±6.74adh1.63±0.03bdfh1.60±0.01dh0.75±0.0013 038.88±371.86dfh166.42±9.02bdfh
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基于UPLC-Orbitrap MS/MS对比分析女贞子不同炮制品中多成分药代动力学特征*
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赵灿楠 1, 2 , 孙淑仃 1, 2, 3 , 郑历史 1, 2, 3 , 赵迪 1, 2, 3 , 李焕茹 1, 2 , 冯素香 1, 2, 3, **
药物分析杂志 | 代谢分析 2024,44(12): 2011-2022
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药物分析杂志 | 代谢分析 2024, 44(12): 2011-2022
基于UPLC-Orbitrap MS/MS对比分析女贞子不同炮制品中多成分药代动力学特征*
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赵灿楠1, 2 , 孙淑仃1, 2, 3, 郑历史1, 2, 3, 赵迪1, 2, 3, 李焕茹1, 2, 冯素香1, 2, 3, **
作者信息
  • 1.河南中医药大学，郑州 450046
  • 2.呼吸疾病中医药防治省部共建协同创新中心，郑州 450046
  • 3.河南省现代中药研发与应用工程研究中心，郑州 450046

    • Tel：15236837705；E-mail：

通讯作者:

**Tel：13526403080；E-mail：
Comparative pharmacokinetic characterization of multi-components in different artifacts of Ligustri Lucidi Fructus based on UPLC-Orbitrap MS/MS*
Can-nan ZHAO1, 2 , Shu-ding SUN1, 2, 3, Li-shi ZHENG1, 2, 3, Di ZHAO1, 2, 3, Huan-ru LI1, 2, Su-xiang FENG1, 2, 3, **
Affiliations
  • 1.Henan University of Chinese Medicine, Zhengzhou 450046, China
  • 2.Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province & Education Ministry of P.R., Zhengzhou 450046, China
  • 3.Henan Engineering Research Center of Modern Chinese Medicine Research, Development and application, Zhengzhou 450046, China
出版时间: 2024-12-31 doi: 10.16155/j.0254-1793.2024-0377
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摘要
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目的：

建立血浆中红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13的超高效液相色谱-质谱分析方法，探究女贞子、酒女贞子、醋女贞子、盐女贞子、清蒸女贞子5种不同炮制品在大鼠体内的药代动力学特征差异。

方法：

SPF级雄性SD大鼠随机分为6组，分别灌胃给予女贞子不同炮制品水提液4.2 g·kg-1（以生药量计），以京尼平苷为内标物，血浆样品经甲醇沉淀蛋白，采用UPLC-MS/MS负离子SIM模式测定不同时间点大鼠血浆中红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷以及女贞苷G13的浓度，Kinetica 5.1软件计算药代动力学参数，GraphPad Prism 8.4.0软件进行数据分析。

结果：

红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷质量浓度在2.00~1 385 ng·mL-1范围内，女贞苷G13质量浓度在1.30~650 ng·mL-1范围内线性关系良好，精密度RSD均<10%，提取回收率均在85%~105%，基质效应和稳定性均符合生物样品的要求。药动学研究结果显示，与生女贞子相比，酒女贞子的毛蕊花糖苷AUC0-∞、MRT0-t、t1/2、Cmax均显著升高（P<0.01），分别为751.36 ng·mL-1·h，5.87 h，377.82 h，38.11 ng·mL-1；盐女贞子的特女贞苷和女贞苷G13 Cmax、AUC0-∞和t1/2均显著升高（P<0.01），Cmax分别为66.45、204.27 ng·mL-1，AUC0-∞分别为342.69、423.44 ng·mL-1·h，t1/2分别为101.64、15.98 h；醋蒸、酒蒸、清蒸女贞子的橄榄苦苷Cmax显著升高（P<0.05），分别为66.81、68.00、66.38 ng·mL-1。醋女贞子的红景天苷和木樨榄苷-11-甲酯AUC0-∞最高，分别为5 782.74、545.26 ng·mL-1·h。

结论：

本研究揭示了女贞子不同炮制品中6个活性成分在体内的变化规律及其差异特点，为女贞子不同炮制品的临床应用提供依据。

女贞子  /  红景天苷  /  木樨榄苷-11-甲酯  /  特女贞苷  /  毛蕊花糖苷  /  橄榄苦苷  /  女贞苷G13  /  炮制  /  超高效液相串联质谱  /  药代动力学  /  临床应用
Objective:

To establish an UPLC-MS method for the analysis of salidroside, methyloleoside, specnuezhenide, acteoside, oleuropein, and G13 in plasma, and the differences in pharmacokinetic profiles of five different concoctions of Ligustri Lucidi Fructus, wine Ligustri Lucidi Fructus, vinegar Ligustri Lucidi Fructus, salt Ligustri Lucidi Fructus and steamed Ligustri Lucidi Fructus in vivo of rats were investigated.

Methods:

SPF-grade male SD rats were randomly divided into 6 groups, and were given 4.2 g·kg-1 of aqueous extracts of different concoctions of Ligustri Lucidi Fructus by gavage (for the amount of raw drug), and the plasma samples were methanol-precipitated proteins with geniposide as the internal standard, and the plasma samples were used to determine salidroside, methyloleoside, specnuezhenide, acteoside, oleuropein, and G13 in the plasma of the rats in the different time points by using the negative-ion SIM mode of UPLC-MS/MS. Kinetica 5.1 software was used to calculate the pharmacokinetic parameters, and GraphPad Prism 8.4.0 software was used to analyze the data.

Results:

The mass concentrations of salidroside, methyloleoside, specnuezhenide, acteoside and oleuropein were in the range of 2.00-1 385 ng·mL-1, and the mass concentration of G13 was in the range of 1.30-650 ng·mL-1, with good linearity, the relative standard deviations of the precision were all less than 10%, the recoveries of the extracts were all in the range of 85%-105%, and the matrix effect and stability were in accordance with the requirements of biological samples. The results of pharmacokinetic study showed that the AUC0-∞, MRT0-t, t1/2, and Cmax of acteoside were significantly higher in wine Ligustri Lucidi Fructus (P<0.01) compared to raw Ligustri Lucidi Fructus, which was 751.36 ng·mL-1·h, 5.87 h, 377.82 h, and 38.11 ng·mL-1, respectively. Cmax, AUC0-∞, and t1/2 were significantly higher (P<0.01) for specnuezhenide and G13 in salt Ligustri Lucidi Fructus compared to raw Ligustri Lucidi Fructus, with Cmax of specnuezhenide and G13 in salt Ligustri Lucidi Fructus were 66.45 ng·mL-1 and 204.27 ng·mL-1, respectively. The AUC0-∞ were 342.69 ng·mL-1 and 423.44 ng·mL-1·h, and t1/2 were 101.64 h and 15.98 h, respectively. Compared to raw Ligustri Lucidi Fructus, the Cmax of oleuropein was significantly higher (P<0.05) in vinegar Ligustri Lucidi Fructus, wine Ligustri Lucidi Fructus, and steamed Ligustri Lucidi Fructus with 66.81 ng·mL-1, 68.00 ng·mL-1, and 66.38 ng·mL-1, respectively. The AUC0-∞ of salidroside and methyloleoside was the highest in vinegar Ligustri Lucidi Fructus, which was 5 782.74 ng·mL-1 and 545.26 ng·mL-1·h, respectively.

Conclusion:

This study reveals the changing law of the six active ingredients in different artillery products of Ligustri Lucidi Fructus in vivo and their different characteristics, which provides a basis for the clinical application of different artillery products of Ligustri Lucidi Fructus.

Ligustri Lucidi Fructus  /  salidroside  /  methyloleoside  /  specnuezhenide  /  acteoside  /  oleuropein  /  G13  /  process  /  UPLC-MS/MS  /  pharmacokinetics  /  clinical applications
赵灿楠, 孙淑仃, 郑历史, 赵迪, 李焕茹, 冯素香. 基于UPLC-Orbitrap MS/MS对比分析女贞子不同炮制品中多成分药代动力学特征*. 药物分析杂志, 2024 , 44 (12) : 2011 -2022 . DOI: 10.16155/j.0254-1793.2024-0377
Can-nan ZHAO, Shu-ding SUN, Li-shi ZHENG, Di ZHAO, Huan-ru LI, Su-xiang FENG. Comparative pharmacokinetic characterization of multi-components in different artifacts of Ligustri Lucidi Fructus based on UPLC-Orbitrap MS/MS*[J]. Chinese Journal of Pharmaceutical Analysis, 2024 , 44 (12) : 2011 -2022 . DOI: 10.16155/j.0254-1793.2024-0377
正文
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女贞子为木犀科植物女贞(Ligustrum lucidum Ait.)的干燥成熟果实，始载于《神农本草经》，具有滋补肝肾、明目乌发之功效[1]。女贞子常用炮制品有生女贞子、酒女贞子、醋女贞子、盐女贞子以及清蒸女贞子。女贞子生品味性微寒，清蒸后可缓解其寒凉之性，滋补肝肾作用增强；酒蒸后可治风虚、补腰膝、黑发强筋；醋蒸后保肝作用增强；盐蒸后入肾引药下行，亦可增强其滋补肝肾、滋阴润燥的作用[2-5]。环烯醚萜苷类以及苯乙醇类是女贞子的主要有效成分[6-10]，研究发现经不同炮制方法加工后有效成分的含量发生显著变化[11-13]，绝大多数化学成分只有入血并维持在一定浓度以上才能发挥药效，所以研究其有效成分的体内代谢规律至关重要。目前对女贞子和酒女贞子体内成分代谢差异的研究较多[14-16]，但对其5种炮制品提取物给药后体外主要差异性成分的体内过程尚未见报道。因此，为进一步探究同批次女贞子不同炮制品中存在显著差异的化学成分在体内的代谢特征，本研究采用UPLC-MS技术对灌胃给予同批次女贞子、酒女贞子、醋女贞子、盐女贞子以及清蒸女贞子5种不同炮制品提取物后大鼠血浆中的6个体外差异性成分进行药代动力学研究，对比女贞子不同炮制品的药代动力学特征，为女贞子不同炮制品的临床合理用药及其药效物质基础研究提供依据。
1　仪器与材料
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1.1　仪器
Orbitrap Fusion Lumos Tribrid三合一超高分辨质谱仪、Vanquish高效液相色谱仪、Xcalibur工作站（ThermoFisher Scientific公司）；MS105DU十万分之一分析天平（梅特勒-托利多（上海）有限公司）；Heraeus Multifuge X1R型冷冻台式高速离心机、SPD 2010-230型离心低温浓缩仪、933型超低温冰箱（Thermo Fisher Scientific公司）；XH-C型振荡器（江苏优卓诺仪器制造有限公司）；BE-3100型混匀超级小精灵（海门市其林贝尔仪器制造有限公司）；Milli-QPOD超纯水仪（Merck公司）。
1.2　药品与试剂
女贞子药材（批号20170601），购自安徽九合堂国药有限公司，经河南中医药大学陈随清教授鉴定为木犀科植物女贞的干燥成熟果实；红景天苷（批号B20504，含量≥98%）、木樨榄苷-11-甲酯（批号B23144，含量≥96%）、特女贞苷（批号B21240，含量≥98%）、橄榄苦苷（批号B20425，含量≥98%）、女贞苷G13（批号B20954，含量≥98%）对照品，上海源叶生物科技有限公司；毛蕊花糖苷（批号MUST-17020715，含量≥99.57%）、京尼平苷（批号MUST-16042018，含量≥99.64%）对照品，成都曼思特生物科技有限公司；甲醇、乙腈、甲酸均为质谱纯，Fisher Scientific公司；超纯水，自制。
1.3　动物
36只清洁级雄性SD大鼠，体质量（280±20）g，购于郑州市惠济区华兴实验动物养殖厂，实验动物许可证号：SCXK（豫）2019-0002，该实验经过由河南中医药大学实验动物伦理委员会批准（批准文号：DWLL 201910323）。饲养条件：湿度（60±5）%，温度22~25 ℃，12 h光照黑暗循环，喂食正常维持饲料，实验前一晚禁食，自由饮水。实验动物的饲养和实验研究符合《河南省实验动物管理条例》。
2　方法与结果
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2.1　定量分析
2.1.1　供试品溶液的制备
取女贞子原药材，除去杂质，洗净，阴干；再取女贞子原药材，分别加入黄酒、米醋、10%盐水、水拌匀，每100 kg女贞子加辅料20 kg[17]，密闭闷润2 h，蒸制8 h，阴干，即得女贞子、酒女贞子、醋女贞子、盐女贞子以及清蒸女贞子5种炮制品。取女贞子不同炮制品粉末（过四号筛）各约2 g，精密称定，分别置于50 mL具塞锥形瓶中，加入80%的甲醇25 mL，称量，超声（700 W，40 kHz）提取1 h，放冷，用80%的甲醇补足减失的量，摇匀，过滤，用0.22 μm微孔滤膜滤过，取续滤液，待测。
2.1.2　测定条件
液相色谱：采用Thermo Scientific Accucore TM C18（100 mm×2.1 mm，2.6 μm）色谱柱，以甲醇（A）-0.1%甲酸水（B）为流动相，梯度洗脱（0~2 min，85%B→70%B；2~4 min，70%B→25%B；4~9 min，25%B；9~12 min，25%B→0%B），流速0.2 mL·min-1，进样量1 μL，进样室温度4 ℃，柱温25 ℃。
质谱：采用ESI离子源负离子检测，扫描模式为SIM模式，鞘气压力3 500 kPa，辅助气体压力700 kPa，扫气压力0 kPa，负离子模式下毛细管电压为2.5 kV，碰撞能量（CE）为20、40、60 eV，离子传输管300 ℃，气化温度275 ℃，扫描范围m/z 100~1 500。
2.1.3　含量测定
取“2.1.1”项供试品溶液，按照“2.1.2”项条件测定，生女贞中红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13的含量分别为2.994 4、1.010 5、10.929 2、0.122 3、1.893 4、3.171 7 mg·g-1。酒蒸女贞子红景天苷、木榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13的含量分别为3.122 4、0.293 6、9.204 9、0.564 0、1.795 0、2.142 6 mg·g-1。醋蒸女贞子红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13的含量分别为3.167 0、0.295 7、10.081 5、0.394 9、1.550 6、3.117 3 mg·g-1。盐蒸女贞子红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13的含量分别为3.142 8、0.303 5、10.693 1、0.540 4、1.445 7、3.153 0 mg·g-1。清蒸女贞子红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13的含量分别为3.161 8、0.250 1、9.304 6、0.617 3、1.708 1、2.648 7 mg·g-1。
2.2　女贞子不同炮制品灌胃溶液的制备
取“2.1.1”各炮制品约200 g，加入10倍量水煎煮2次，每次1 h，过滤，滤液浓缩至1.26 g·mL-1生药的药液，即得女贞子不同炮制品灌胃溶液。按照4.2 g·kg-1生药量灌胃给予女贞子不同炮制品灌胃溶液，实际给药剂量为生女贞子红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13分别为12.576 5、4.244 1、45.902 6、0.513 7、7.952 3、13.321 1 mg·kg-1。酒蒸女贞子红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13分别为13.114 1、1.233 1、38.660 6、2.368 8、7.539 0、8.998 9 mg·kg-1。醋蒸女贞子红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13分别为13.301 4、1.241 9、42.342 3、1.658 6、6.512 5、13.092 7 mg·kg-1。盐蒸女贞子红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13分别为13.199 8、1.274 7、44.911 0、2.269 7、6.071 9、13.242 6 mg·kg-1。清蒸女贞子红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13分别为13.279 6、1.050 4、39.079 3、2.592 7、7.174 0、11.124 5 mg·kg-1。
2.3　动物分组与给药
36只大鼠适应性喂养7 d后，随机分为6组，组别为空白组、生女贞子组、酒蒸女贞子组、醋蒸女贞子组、盐蒸女贞子组、清蒸女贞子组，每组6只。分别灌胃女贞子不同炮制品灌胃溶液，分别于给药前和给药后0.083、0.17、0.25、0.5、0.75、1、2、4、6、8、12、18、24 h尾静脉取血约400 μL，置含肝素钠抗凝剂的离心管中，并在取血后及时为大鼠补充等量生理盐水。血液样本静置后，置4 ℃离心机中3 000 r·min-1离心15 min，分离血浆，于-80 ℃冻存待测。
2.4　溶液的制备
2.4.1　对照品储备液
精密称取红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13对照品各约10 mg，分别置100 mL量瓶中，加甲醇稀释至刻度，作为对照品储备液。
2.4.2　内标溶液
精密称取京尼平苷（IS）对照品约10 mg，置100 mL量瓶中，加甲醇稀释至刻度，作为内标储备液。精密量取内标储备液适量，用甲醇稀释成质量浓度为55 ng·mL-1的内标溶液。
2.4.3　混合对照品溶液
精密量取对照品储备液适量，加甲醇梯度稀释制备质量浓度红景天苷、木樨榄苷-11-甲酯、特女贞苷为2~1 000 ng·mL-1，毛蕊花糖苷为3~1 400 ng·mL-1，橄榄苦苷为2~1 200 ng·mL-1，女贞苷G13为1~650 ng·mL-1的混合对照品溶液。
2.4.4　混合质控溶液
精密量取对照品储备液适量，加甲醇稀释制备得到低、中、高3个对应质量浓度的混合对照品溶液，其中红景天苷质量浓度为4.2、42、525 ng·mL-1；木樨榄苷-11-甲酯质量浓度为4、40、500 ng·mL-1；特女贞苷质量浓度为4.04、40.4、505 ng·mL-1；毛蕊花糖苷质量浓度为5.54、55.4、692.5 ng·mL-1；橄榄苦苷质量浓度为4.88、48.8、610 ng·mL-1；女贞苷G13质量浓度为2.6、26、325 ng·mL-1的混合质控溶液。
2.5　血浆样品处理
精密吸取血浆样品100 μL于1.5 mL离心管中，加入内标溶液50 μL，加甲醇400 μL，涡旋（2 000 r·min-1）15 min，离心（12 000 r·min-1，4 ℃）10 min。取上清液，于离心浓缩仪中吹干，残渣加50%甲醇100 μL复溶，涡旋（2 000 r·min-1）5 min，离心（14 000 r·min-1，4 ℃）10 min，取上清液进样分析。部分血浆样品的高浓度时间点采取稀释2倍进样。
2.6　色谱及质谱条件
进样量5 μL，其他同“2.1”项下色谱及质谱条件。
2.7　数据处理
采用Kinetica 5.1药物代谢动力学分析软件非房室模型分析法计算各给药组中红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷等6个成分的药代动力学参数，采用GraphPad Prism 8.4.0软件绘制药时曲线并进行单因素方差分析。
2.8　方法学考察
2.8.1　专属性
取大鼠空白血浆100 μL，除用甲醇代替内标溶液外，其余按“2.5”项下方法处理制备空白血浆。精密量取红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13的对照品储备液适量，用甲醇稀释成400 ng·mL-1的混合对照品溶液；精密量取空白血浆100 μL，置1.5 mL离心管中，精密加入混合对照品溶液50 μL，按“2.5”项下自“加入内标溶液50 μL”起操作，配制得到空白血浆加入混合对照品和内标的大鼠血浆样品。取大鼠灌胃给药后的血浆样品，按“2.5”项下方法制备大鼠给药后血浆样品溶液。以上溶液按“2.6”项下条件进样测定，结果见图1。
结果显示，红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13、京尼平苷保留时间分别为2.88、4.08、4.96、4.73、5.20、5.34、0.93 min，6个待测成分及内标京尼平苷分离度良好，无内源及外源性干扰，方法专属性良好。
2.8.2　线性范围
分别精密量取不同浓度梯度的混合对照品溶液50 μL和内标溶液50 μL，于离心浓缩仪中吹干，加入空白血浆100 μL混匀，按“2.5”项方法处理血浆样品后进行分析，以血药浓度X为横坐标，以待测成分与内标物峰面积的比值Y为纵坐标，得到相应的线性回归方程。
大鼠血浆中6个成分在其线性范围内线性关系良好，各成分标准曲线相关系数r均>0.990 0，见表1。
2.8.3　精密度与准确度
取“2.4.4”项下的高、中、低3种质量浓度的混合质控溶液各100 μL，于离心浓缩仪中吹干，分别加入空白血浆100 μL混匀，得低、中、高3个质量浓度的质控(QC)样品。混匀制成高、中、低3种质量浓度的QC样品。按“2.5”处理血浆样品后进行分析。日内精密度每一质量浓度平行6份样分别测定，日间精密度用6个平行样品连续测定3 d，计算日间及日内准确度、精密度。准确度用相对误差RE表示，精密度用相对标准偏差RSD表示。结果显示，6个成分日内、日间精密度的RSD范围分别为1.5%~9.9%、0.33%~6.4%；日内、日间准确度的RE范围分别为-7.8%~9.2%、-6.3%~7.6%，RSD均<10%，准确度在±10%的范围内，符合要求。说明该方法的准确度符合生物样品分析方法指导原则的要求。
2.8.4　基质效应和提取回收率
按“2.8.3”项下方法制备低、中、高3个质量浓度的QC样品，按“2.6”项下的条件进样分析，记录成分峰面积与内标峰面积比值（A）；取大鼠空白血浆100 μL，加甲醇400 μL沉淀蛋白，涡旋后离心10 min（12 000 r·min-1，4 ℃），取上清液于离心浓缩仪中吹干，残渣加入低、中、高3个质量浓度的混合质控溶液及内标溶液各50 μL，涡旋后离心10 min（12 000 r·min-1，4 ℃），取上清进样分析，记录成分峰面积与内标峰面积比值（B）。另取纯水100 μL，加甲醇400 μL，于离心浓缩仪中吹干，残渣加入低、中、高3个质量浓度的混合质控溶液及内标溶液各50 μL，涡旋后离心10 min（12 000 r·min-1，4 ℃），取上清进样分析，得到成分峰面积与内标峰面积比值（C）。提取回收率=A/B×100%；基质效应=A/C×100%，每个质量浓度样品平行6份样品。
如表2所示，6个成分的提取回收率在87.1%~100.2%，基质效应在92.7%~102.3%，表明提取方法精确可重复，且待测成分不受血中成分干扰，符合方法学要求。
2.8.5　稳定性
取“2.8.3”项下高、中、低3种质量浓度的QC样品（各平行6份），分别测定各浓度成分的短期、冻融、长期稳定性。（1）短期稳定性：将样品溶液室温（25 ℃）放置24 h；（2）冻融稳定性：将样品溶液置于-80 ℃下24 h，取出后室温下自然解冻，后再置于-80 ℃下24 h，如此反复冻融循环3次；（3）长期稳定性：将样品溶液于-80 ℃保存30 d。将样品分别按“2.5”项下方法处理后进样分析，计算稳定性。结果见表3，稳定性良好。
2.9　药代动力学研究
大鼠分别灌胃女贞子不同炮制品水提液后，采集不同时间点血浆样品，血浆样品采集方法按“2.3”项进行，血浆样品处理方法按“2.5”项进行，利用上述所建立的UPLC-MS/MS方法测定不同采样点各成分的血药浓度，Kinetica 5.1药物代谢动力学分析软件进行非房室模型拟合，计算各个成分的达峰时间(Tmax)、达峰浓度(Cmax)等药代动力学参数，采用GraphPad Prism软件进行数据分析并绘制药时曲线图。5种炮制品各成分平均血药浓度-时间曲线如图2~图7所示，药代动力学参数如表4~9所示。
3　讨论
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大鼠灌胃给予女贞子5种不同炮制品后，女贞子不同炮制品中6个成分均可在口服给药后1 h内达到最高血药浓度，说明这些成分均可被机体迅速吸收。女贞子不同炮制品含量测定结果显示，红景天苷在药材中含量较低但是其在大鼠血浆中的暴露量大血药浓度高，生物利用度较高，且文献报道红景天苷具有抗骨质疏松、保肝护肾、抗氧化应激等药理作用[18]，说明红景天苷可能是女贞子发挥药效的关键成分。醋女贞子中红景天苷和木樨榄苷-11-甲酯的AUC0-∞较其他4种炮制品显著升高（P<0.01或P<0.05），据文献报道红景天苷能有效缓解CCl4诱导的小鼠肝纤维化[19]，木樨榄苷-11-甲酯对Hep-G2细胞具有强细胞毒作用，且醋可引药入肝[20]，推测醋蒸更有利于女贞子在机体内发挥抗肝纤维化及抗肝癌的药理作用，并增强其保肝作用。与生女贞子相比，酒女贞子毛蕊花糖苷的AUC0-∞、MRT0-t、t1/2、Cmax均显著升高（P<0.01），说明酒蒸后毛蕊花糖苷的暴露量增加且在体内持续时间延长，推测可使其发挥长效作用。文献研究表明，毛蕊花糖苷能够有效减少氧化低密度脂蛋白诱导的巨噬细胞泡沫化[21]，且临床上患有动脉粥样硬化的患者少量饮酒可以增加血液循环舒张血管，因此推测在临床上治疗动脉粥样硬化可以优先选择酒蒸女贞子入药。
生女贞子和盐女贞子中特女贞苷和女贞苷G13的灌胃剂量相似，但与生女贞子相比，盐女贞子中特女贞苷和女贞苷G13的Cmax、AUC0-∞以及t1/2均显著升高（P<0.01），说明盐蒸可以促进机体对特女贞苷和女贞苷G13的吸收并提高其生物利用度，现代药理研究表明特女贞苷可以抑制破骨细胞分化作用[22]，女贞苷G13对大鼠骨髓间充质干细胞的碱性磷酸酶活性有刺激作用[23]，且盐制后可提高骨密度、骨生长因子[24]，因此推测在临床上治疗骨质疏松病人时可以优先选用盐蒸女贞子。与生女贞子相比，醋蒸、酒蒸、清蒸女贞子橄榄苦苷的Cmax显著升高（P<0.05），说明醋蒸、酒蒸、清蒸有利于机体对橄榄苦苷的吸收，橄榄苦苷具有降血糖、降血脂等多种药理作用[25]，因此推测醋蒸、酒蒸、清蒸可能会增强女贞子改善糖尿病的药理作用。
本研究所建立的UPLC-MS/MS分析方法简便、快速、灵敏，适用于大鼠灌胃女贞子不同炮制品提取物后6个活性成分的药代动力学研究。本研究结果补充了女贞子不同炮制品提取物在大鼠体内的药动学特征，为女贞子不同炮制品的临床应用及后续的相关研究提供了依据。
基金
收起
  • *国家自然科学基金项目(No.82374041)
  • 河南省中医药科学研究专项课题(2023ZY1029)
文献
收起
参考文献 引证文献
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2024年第44卷第12期
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doi: 10.16155/j.0254-1793.2024-0377
  • 接收时间：2024-06-05
  • 首发时间：2026-03-13
  • 出版时间：2024-12-31
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  • 收稿日期：2024-06-05
基金
*国家自然科学基金项目(No.82374041)
河南省中医药科学研究专项课题(2023ZY1029)
作者信息
    1.河南中医药大学，郑州 450046
    2.呼吸疾病中医药防治省部共建协同创新中心，郑州 450046
    3.河南省现代中药研发与应用工程研究中心，郑州 450046

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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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