基于“姜制温散”理论的建昌帮天麻炮制的“药性-药效-效应成分”关联的炮制作用变化机理研究

Migraine is a kind of refractory vascular spasm and prone to dizziness, seizures, or vascular dementia syndrome and so on. It is often caused by deficiency body and windy. Owe to the chemical drug application limitations, TCM is often used the theory of “Qu feng zhitong, warming channel stodispel cold medicine prescription”. Gastrodia elata with leve and sweet is the first medicine as for “Qufengzhitong” .Ginger is the goods with symplectic and warm and have a wind dispersing cold by warming, analgesic, antiemetic and eliminating phlegm. It is also commonly used in processing materials. However, both the processing theory of that "Gastrodia elata processed by Ginger called as Jianchang Gang helps increase its efficacy is right" and the current reports were failed to clear effect components of ginger processing changes on Gastrodia elata, and the processing mechanism is not clear. Preliminary study showed that it not only effects its drug properties, but also its gastrodin content and other components with Gastrodia elata processed by Ginger and improve the ability of anti vertigo and learning ability for dementia model rats, but failed to carry out the research from the overall efficacy, efficacy of composition, role change effect of processing components is not clear.In this study, the integrated uses of modern analytical ways, metabolic technology and modern means of statistical analysis, the content changes by the theory of “Ginger dispersing cold by warming”, to carry out study on the resistance of the processed efficacy and composition, correlation analysis of data of resistance efficacy component, and clear effect components, clarify the gun made of material basis for efficacy changes. It will reveal its processing mechanism that is scientific and effective to provide data support technology of Gastrodia elata processed by Ginger .

偏头痛，是一种难治性血管痉挛性疾病，易致眩晕、惊厥或血管性痴呆等证，素以体虚而感风邪为主因。由于化学药物应用的局限，中医常以祛风止痛、温经散寒等药取得良好疗效。天麻性平，为祛风止痛之要药；生姜辛温，具发散风寒，温中止呕、祛痰之功，也是常用炮制辅料。然而，无论是“建昌帮”提出天麻姜制符合药效增强的炮制理论，还是目前的文献报道，均未明确姜天麻作用变化的效应成分，炮制机理不明。前期研究表明，姜制天麻后，不仅影响药性，而且对天麻素及其他成分也产生影响，并能提高模型鼠抗眩晕和学习记忆能力，但未能从药性、整体药效和效应成分等方面深入研究，未阐明变化后的有效组分（群）。为此，本课题拟结合现代分析手段、代谢组学技术和统计学等方法，通过“姜制温散”炮制后的药性变化、药效和成分等研究内容，分析药性-药效-成分等关联数据，阐明炮制前后作用变化的药效物质基础，揭示其炮制机理，为姜天麻炮制的科学合理性提供数据支撑

项目背景：姜天麻为江西“建昌帮”地方炮制特色饮片，但临床疗效主要基于经验判断，炮制变化机理仍缺乏现代研究基础。该药帮提出天麻经姜制后，可增强天麻抗眩晕、止痛之效，而天麻为治偏头痛之要药。因此，本项目研究姜天麻炮制作用机理，契合中药炮制目的。由于天麻炮制后后差异性成分较多，但变化后的成分又是影响药效变化的关键。因此，本项目运用UHPLC-Q-TOF-MS、LC-MS-MS、HPLC等多种分析手段，从炮制后出现的成分、药性和药效等方面开展研究，以阐明天麻炮制作用变化机理。.主要研究内容：本研究主要从天麻经姜制后发生的成分、药性和药效等变化方面开展研究。优选了姜天麻提供工艺参数；开展了天麻不同炮制品之间的主成分变化差异、稳定和非稳定性挥发性等成分研究；以及天麻炮制前后对镇痛、抗惊厥和抗偏头痛等作用的影响研究；借助网络药理学，结合天麻炮制后成分、药性和药效研究资料，分析了成分、靶点和疾病之间的关系以及炮制后的效应成分，以此探讨了天麻炮制作用变化机理。.3重要结果：.① 采用响应曲面法，优化了姜天麻有效成分提取工艺参数；.② 建立了天麻素含量的测定方法，并明确了姜天麻与其他炮制品中天麻素的含量差异；.③ 天麻经姜制后发生炮制变化的主要效应成分为天麻素和巴利森苷类，以及生姜中β-谷甾醇等；.④ 天麻经姜制后药效增强主要机理，其作用路径可能是通过降低NO、CGRP和提高ET、DA、5-HT的含量，以改善偏头痛症状。.4关键数据：一是天麻经姜制后发生的成分、药性和药效等方面的变化；二是为阐述天麻炮制机理奠定基础。.5科学意义：.“建昌帮”姜天麻目前的临床应用，仍局限于地方经验，未见现代研究内容，临床推广受限。本研究初步明确了“建昌帮”姜制天麻炮制后药效物质基础，揭示了其炮制作用机理，为姜天麻在临床应用提供了科学依据，也为姜天麻炮制品在生产、炮制加工、质量控制等方面提供了科学依据。同时，为寻找治疗偏头痛新药来源提供了契机，并为开展天麻炮制后的变化成分对药效作用机制奠定了基础。