Deng Xin, Lei Hong-Yuan, Ren Yong-Shen, Ai Jiao, Li Yan-Qiu, Liang Shuai, Chen Lin-Lin, Liao Mao-Chuan
School of Pharmacy, South-Central Minzu University, Wuhan, China; State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau.
School of Pharmacy, South-Central Minzu University, Wuhan, China.
J Ethnopharmacol. 2023 Jan 10;300:115677. doi: 10.1016/j.jep.2022.115677. Epub 2022 Sep 3.
Bioactive substance identification is always the focal point and the main challenge in Chinese herbal medicine (CHM). Most CHM present multiple efficacies and multiple tropisms, which has improved the application accuracy of CHM, and is worthy of further study. In this article, the concept of "multi-tropism efficacy of CHM" has been proposed for the first time. In addition, it is hypothesized that the different components in CHM can be classified based on their efficacy status.
The spectrum-effect relationship between the fingerprint and efficacy was established to identify the efficacy status of components. This provided a practical, efficient and accurate way to identify the bioactive substances from a complex CHM system.
The network pharmacology approach was applied to preliminarily analyze the potential antibacterial compounds and mechanisms of HQ. Furthermore, its chemical fingerprint was established and the characteristic peaks were identified by LC-MS/MS. The antibacterial and anti-inflammatory bioactivities of HQ were determined to evaluate its pharmacological effect of heat-clearing and detoxification, and its anticoagulation activity was determined to evaluate its heat-clearing and tocolysis effects. The spectrum-effect relationships were assessed by gray correlation analysis to discriminate the status of active components in HQ with different efficacies.
Network pharmacology analysis revealed apigenin, wogonin, baicalein, acacetin, β-sitosterol, baicalin, eugenol, moslosooflavone, palmitic acid, oroxylin-A 7-O-glucuronide, and scutevulin as the potential active compounds responsible for the efficacy of HQ against both E. coli and S. aureus. The spectrum-effect relationship was utilized to reveal the orientation activities, with the results as follows: 1) The main basic-efficacy components in HQ with antibacterial, anti-inflammatory, and anticoagulant effects were P5, P8, P9, P15, P18, P19, P20; while the general basic-efficacy components were P2, P3, P6, P7, P11, P14, P21, P22, P28. 2) The main efficacy-oriented components in HQ with antibacterial effects on E. coli were P1, P12, P17, while the general efficacy-oriented compound was P10, P24, P25, P26, P27; the main efficacy-oriented in HQ with antibacterial effects on S. aureus were P14 and the general efficacy-oriented components were P1, P12, P26, P29, P30, respectively. 3) The main efficacy-oriented components with anti-inflammatory activity were P14, P24, P25, P27, and P30, while the general efficacy-oriented components were P13, P23, P26. 4) The main efficacy-oriented compounds in HQ with effects on anticoagulation were P6 and P22; these acted by prolonging APTT through the intrinsic coagulation pathway and PT through the extrinsic coagulation pathway, respectively. 5) The pharmacodynamic status classification of Scutellaria baicalensis ingredients were confirmed by nine reference compounds exemplarily.
This work established a novel strategy for active compound efficacy status identification in multi-tropism Chinese herbal medicine (Scutellaria baicalensis Georgi) based on multi-indexes spectrum-effect gray correlation analysis, the method is scientific feasible and can be applied to the effective substances identification and quality control of other CHM.
生物活性物质的鉴定一直是中药的重点和主要挑战。大多数中药具有多种功效和多种归经，这提高了中药的应用准确性，值得进一步研究。本文首次提出了“中药多归经功效”的概念。此外，推测中药中的不同成分可根据其功效状态进行分类。
建立指纹图谱与功效之间的谱效关系，以确定成分的功效状态。这为从复杂的中药体系中鉴定生物活性物质提供了一种实用、高效且准确的方法。
应用网络药理学方法初步分析黄芩的潜在抗菌化合物及作用机制。此外，建立其化学指纹图谱，并通过液相色谱 - 串联质谱法鉴定特征峰。测定黄芩的抗菌、抗炎生物活性以评估其清热解毒的药理作用，测定其抗凝活性以评估其清热安胎作用。通过灰色关联分析评估谱效关系，以区分黄芩中不同功效活性成分的状态。
网络药理学分析表明，芹菜素、汉黄芩素、黄芩苷元、刺槐素、β - 谷甾醇、黄芩苷、丁香酚、莫洛索黄酮、棕榈酸、木犀草素 - 7 - O - 葡萄糖醛酸苷和野黄芩素是黄芩对大肠杆菌和金黄色葡萄球菌发挥功效的潜在活性化合物。利用谱效关系揭示了定向活性，结果如下：1）黄芩中具有抗菌、抗炎和抗凝作用的主要基本功效成分是P5、P8、P9、P15、P18、P19、P20；一般基本功效成分是P2、P3、P6、P7、P11、P14、P21、P22、P28。2）黄芩中对大肠杆菌有抗菌作用的主要功效导向成分是P1、P12、P17，一般功效导向化合物是P10、P24、P25、P26、P27；黄芩中对金黄色葡萄球菌有抗菌作用的主要功效导向成分是P14，一般功效导向成分分别是P1、P12、P26、P29、P30。3）具有抗炎活性的主要功效导向成分是P14、P24、P25、P27和P30，一般功效导向成分是P13、P23、P26。4）黄芩中具有抗凝作用的主要功效导向化合物是P6和P22；它们分别通过内源性凝血途径延长活化部分凝血活酶时间（APTT）和通过外源性凝血途径延长凝血酶原时间（PT）来发挥作用。5）以9种对照品为例证实了黄芩成分的药效学状态分类。
本研究基于多指标谱效灰色关联分析，建立了一种鉴定多归经中药（黄芩）中活性化合物功效状态的新策略，该方法科学可行，可应用于其他中药有效物质的鉴定和质量控制。
