| 引用本文: | 续艳丽,李少泓,李坚,李晓春,朱仁愿,张启立,武晓玉,段文达,夏鹏飞,赵磊.经典名方芍药甘草汤解痉功效的关键质量属性研究[J].中国现代应用药学,2023,40(6):721-729. |
| XU Yanli,LI Shaohong,LI Jian,LI Xiaochun,ZHU Renyuan,ZHANG Qili,WU Xiaoyu,DUAN Wenda,XIA Pengfei,ZHAO Lei.Research on key quality attributes of Spasmolysis effect of the famous classical formula Shaoyao Gancao Decoction[J].Chin J Mod Appl Pharm(中国现代应用药学),2023,40(6):721-729. |
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| 经典名方芍药甘草汤解痉功效的关键质量属性研究 |
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续艳丽1,2, 李少泓3, 李坚2, 李晓春2, 朱仁愿2, 张启立1, 武晓玉1,4,5, 段文达1,4,5, 夏鹏飞1,4,5, 赵磊1,4,5
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1.甘肃中医药大学药学院, 兰州 730099;2.兰州市食品药品检验检测研究院, 兰州 730050;3.无锡市第二人民医院, 江苏 无锡214000;4.甘肃中医药大学甘肃省高校中藏药化学与质量研究省级重点实验室, 兰州 730000;5.甘肃省道地药材质量标准化技术研究与推广工程实验室, 兰州 730000
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| 摘要: |
| 目的 基于血清药物化学、网络药理学和体外实验验证，阐明芍药甘草汤(Shaoyao-Gancao decoction，SGD)治疗痉挛性疾病的关键质量属性。方法 采用UHPLC-Q-Exactive Orbitrap MS技术对SGD体内入血移行成分进行分析鉴定；利用Cytoscape构建“入血成分-解痉靶点-通路”网络图，筛选SGD解痉核心功效成分；通过离体肠平滑肌实验对核心成分进行验证，明确SGD解痉功效的关键质量属性。结果 据高分辨质谱提供的精确分子量和碎片离子信息，结合对照品比对和相关文献报道，共鉴定出17个SGD入血原型成分，分别为氧化芍药苷、芍药内酯苷、芍药苷、异甘草苷、甘草苷、甘草酸、苯甲酰芍药苷、甘草查尔酮B、芒柄花苷、异甘草素、甘草素、甘草查尔酮A、甘草查尔酮C、光甘草定、甘草次酸、没食子酸。网络药理学预测SGD中光甘草定、甘草素、芍药内酯苷、芍药苷和苯甲酰芍药苷度值较高，可能通过GRIN2A、VCP、ABCB1、CYP2C9、CYP3A4、CHRNB2、SNCA等靶点，作用于药物代谢-细胞色素P450、神经活性配体-受体相互作用、cAMP、钙信号通路等发挥解痉作用。生物活性测定结果表明，芍药苷、甘草素、芍药内酯苷、光甘草定和苯甲酰芍药苷均可降低乙酰胆碱(acetylcholine，Ach)引起的离体肠平滑肌收缩张力，是SGD解痉功效的关键质量属性，其中芍药苷和甘草素解痉效果较强，与Ach模型组比较，差异具有统计学意义(P<0.05或P<0.01)。结论 本实验构建经典名方芍药甘草汤关键质量属性筛选方法，明确SGD解痉功效的关键质量属性，为SGD的精准质量控制及其产品二次开发提供实验依据。 |
| 关键词: 芍药甘草汤 经典名方 UPLC-Q-Exactive Orbitrap MS 血清药物化学 网络药理学 痉挛 关键质量属性 |
| DOI：10.13748/j.cnki.issn1007-7693.20222666 |
| 分类号:R961 |
| 基金项目:国家自然科学基金项目(82160457)；兰州市科技计划项目(2021-1-185)；甘肃省药品监督管理局科研项目(2020GSMPA027)；甘肃省自然科学基金项目(21JR7RA564)；甘肃省高校中(藏)药化学与质量研究省级重点实验室开放基金(zzy-2022-07) |
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| Research on key quality attributes of Spasmolysis effect of the famous classical formula Shaoyao Gancao Decoction |
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XU Yanli1,2, LI Shaohong3, LI Jian2, LI Xiaochun2, ZHU Renyuan2, ZHANG Qili1, WU Xiaoyu1,4,5, DUAN Wenda1,4,5, XIA Pengfei1,4,5, ZHAO Lei1,4,5
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1.College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730099, China;2.Lanzhou Institute for Food and Drug Control, Lanzhou 730050, China;3.Wuxi No.2 People’s Hospital, wuxi 214000, China;4.Key Laboratory of Chemistry and Quality for Traditional Chinese Medicines, College of Gansu Province, Gansu University of Chinese Medicine, Lanzhou 730000, China;5.Gansu Province Engineering Laboratory for TCM Standardization Technology and Popularization, Lanzhou 730000, China
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| Abstract: |
| OBJECTIVE To elucidate the critical quality attributes of Shaoyao Gancao decoction(SGD) in the treatment of spasmodic diseases based on serum pharmacochemistry, network pharmacology and isolated intestinal smooth muscle contraction experiments. METHODS The blood migration components in SGD were analyzed and identified by UHplC-Q-Exactive Orbitrap MS. Cytoscape software was used to construct the network diagram of "blood components- spasmolytic target-pathway" and screen the core functional components of SGD in spasmolytic. The core components were verified by isolated intestinal smooth muscle test, and the critical quality attributes of SGD spasmolytic efficacy were clarified. RESULTS According to the accurate molecular weight and fragment ion information provided by high resolution mass spectrometry, combined with standard substance comparison and relevant literature reports, a total of 17 SGD prototype components were identified, included oxypaeoniflorin, albiflorin, paeoniflorin, isoliquiritin, liquiritin, glycyrrhizic acid, benzoylpaeoniflorin, licochalcone B, ononin, liquiritigenin, iso liquiritigenin, licochalcone A, licochalcone C, glabridin, glycyrrhetinic acid, gallic acid. Network pharmacology predicted that the key SGD antispasmodic active ingredients of glabridin, liquiritigenin, albiflorin, paeoniflorin and benzoylpaeoniflorin may exert antispasmodic effects through GRIN2A, VCP, ABCB1, CYP2C9, CYP3A4, CHRNB2, SNCA and other targets, acting on drug metabolism-cytochrome P450, neuroactive ligand- receptor interactions, cAMP, calcium signaling pathway, etc. Verification tests showed that the glabridin, liquiritigenin, albiflorin, paeoniflorin and benzoylpaeoniflorin could reduce the maximum contractile evoked by acetylchloine, and albiflorin and paeoniflorin exerted significant spasmolytic effects with the inhibitory response for acetylcholine evoked contraction(P<0.05 or P<0.01). CONCLUSION The critical quality attributes of SGD antispasmolysis efficacy are determined by establishing the screening method of the classic decoction standard, which provide experimental basis for the accurate quality control of SGD and the secondary development of SGD products. |
| Key words: Shaoyao Gancao decoction classic prescription UHPLC-Q-Exactive Orbitrap MS serum pharmacochemistry network pharmacology spasticity critical quality attributes. |
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