利用网络药理学方法研究芪桂痛风片的药效物质基础与分子作用机制(1)
[摘要]该研究采用网络药理学方法结合分子相似性比较来探索芪桂痛风片治疗痛风的药效物质基础和分子作用机制。分子相似性结果表明芪桂痛风片中木犀草素、异泽兰黄素、金合欢素-7-O-β-D-吡喃半乳糖苷及其光学异构体等黄酮类化合物与金石欢素(acacetin)具有较高的相似性，提示其对痛风有一定的治疗作用，进一步的分子对接和网络分析发现芪桂痛风片中网络度大于8的dongbeinine，去氢浙贝母碱-N-氧化物和浙贝母碱-N-氧化物等9个生物碱类化合物通过作用于黄嘌呤氧化酶，基质金属蛋白酶9，5-脂氧合酶激活蛋白和蛋白酪氨酸激酶等22个靶点来抑制新尿酸形成、缓解已形成尿酸引发的炎症反应、调节机体免疫应答，由此揭示出这些化合物可能为芪桂痛风片的主要药效物质基础，同时也揭示了其治疗痛风的分子作用机制，印证了芪桂痛风片整体的药效作用特征并为其进一步的效应物质基础和作用机制探索提供理论依据。
[关键词]痛风;芪桂痛风片;网络药理学;分子相似性;分子对接
Study on effective substance basis and molecular mechanism of Qigui
Tongfeng tablet using network pharmacology method
KE Zhi-peng1，2， ZHANG Xin-zhuang1，2， DING Yue1，2， CAO Liang1，2， LI Na1，2， DING Gang1，2， WANG Zhen-zhong1，2， XIAO Wei1，2*
(1.Jiangsu Kanion Pharmarceutical Co.， Ltd.， Lianyungang 222001， China;
2. State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process， Lianyungang 222001， China)
[Abstract]Qigui Tongfeng tablet(QLTFT) is a traditional Chinese medicine with good effect for treating gout. Here， network pharmacology method and molecular similarity analysis were utilized to study the effective substance basis and molecular mechanism of the QLTFT on the gout. The similarity to the medicinal compounds is reflected in the Tanimoto coefficient that gives the structural similarity of two compounds. Operationally， similar modifiers were described as pairs of concepts with a similarity score of 0.500. The results of the molecular similarity analysis suggested that the flavonoids in QLTFT could be new leads for gout. Furthermore， complex biological systems may be represented and analyzed as computable networks. Two important properties of a network were degree and betweenness. Nodes with high degree or high betweenness may play important roles in the overall composition of a network. And the results of network analysis showed that dongbeinine， verticinone-N-oxide， verticine N-oxide， peimine， peiminine， isobaimonidine， dongbeirine， peimisine and simiarenol which with high degree acted on xanthine dehydrogenase/oxidase， matrix metalloproteinase-9， an arachidonate 5-lipoxygenase-activating protein， tyrosine-protein kinase and etc. Inhibition of these targets can prevent the formation of uric acid， reduce inflammation by uric acid and regulate the body′s immune response. Thus， these compounds may be the main effective substance basis. The research results not only reveals its molecular mechanism， but also provide a theoretical basis for the quality control of drugs and clinical application. (柯志鹏 张新庄 丁玥 曹亮 李娜 丁岗 王振中 萧伟)
[关键词]痛风;芪桂痛风片;网络药理学;分子相似性;分子对接
Study on effective substance basis and molecular mechanism of Qigui
Tongfeng tablet using network pharmacology method
KE Zhi-peng1，2， ZHANG Xin-zhuang1，2， DING Yue1，2， CAO Liang1，2， LI Na1，2， DING Gang1，2， WANG Zhen-zhong1，2， XIAO Wei1，2*
(1.Jiangsu Kanion Pharmarceutical Co.， Ltd.， Lianyungang 222001， China;
2. State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process， Lianyungang 222001， China)
[Abstract]Qigui Tongfeng tablet(QLTFT) is a traditional Chinese medicine with good effect for treating gout. Here， network pharmacology method and molecular similarity analysis were utilized to study the effective substance basis and molecular mechanism of the QLTFT on the gout. The similarity to the medicinal compounds is reflected in the Tanimoto coefficient that gives the structural similarity of two compounds. Operationally， similar modifiers were described as pairs of concepts with a similarity score of 0.500. The results of the molecular similarity analysis suggested that the flavonoids in QLTFT could be new leads for gout. Furthermore， complex biological systems may be represented and analyzed as computable networks. Two important properties of a network were degree and betweenness. Nodes with high degree or high betweenness may play important roles in the overall composition of a network. And the results of network analysis showed that dongbeinine， verticinone-N-oxide， verticine N-oxide， peimine， peiminine， isobaimonidine， dongbeirine， peimisine and simiarenol which with high degree acted on xanthine dehydrogenase/oxidase， matrix metalloproteinase-9， an arachidonate 5-lipoxygenase-activating protein， tyrosine-protein kinase and etc. Inhibition of these targets can prevent the formation of uric acid， reduce inflammation by uric acid and regulate the body′s immune response. Thus， these compounds may be the main effective substance basis. The research results not only reveals its molecular mechanism， but also provide a theoretical basis for the quality control of drugs and clinical application. (柯志鹏 张新庄 丁玥 曹亮 李娜 丁岗 王振中 萧伟)