基于组效关系的苗药“头花蓼”质量评价研究

The whole herb of Polygonum capitatum Buch.-Ham. ex D. Don Prodr (Tou-Hua-Liao, THL) is one of the six emphatically developed Miao medicines included in the plan of Chinese material medica modernization of Guizhou province. We previously studied this herbal medicine from aspects of crude drug, preparations and new drug development, resulting in the establishment and approval of GAP bases, marketing of three THL-based preparations, i.e., Re-Lin-Qing Kili, Ning-Bi-Tai Jiaonang, and Si-Ji-Cao Keli, as well as the ongoing phase II clinical trial of two compound prescriptions containing THL. However, since the chemical constituents of THL are very complex and the effective principles remains unclear, a reasonable and effective quality assessment system of THL is still required. The proposed study aimed at clarifying the composition-activity relationship by combination of various modern analysis and separation techniques and multi-index evaluation of antibacteria and anti-inflammatoary activities. The composition-activity relationship will be elucidated from aspects of pharmacological activity, contribution to the efficacy, and influence (synergy or antagonism) on the activity. A quality assessment system will be established based on the revealed relationship. Results obtained from this study will not only provide valuable scientific evidence for the utilization of THL and its preparations, but can also facilitate research and development of active composition-based new drug of THL.

头花蓼是贵州省中药现代化重点发展的六大苗药之一。我们前期对其进行了药材、产品及创新性新药三个层面的研究，完成了GAP种植基地的建设和认证，研制成功以头花蓼为原料的三个中药产品，即热淋清颗粒，宁泌泰胶囊以及四季草颗粒，两个复方新药正在进行二期临床研究。 这些研究结果表明头花蓼具有良好的临床应价值。但是，由于头花蓼化学成分复杂，药效物质不明确，因此一直缺乏合理有效的质量评价体系。为此，本研究以揭示头花蓼的"组-效关系"为主要目标，采用多种现代分离分析技术，结合多指标抗菌抗炎活性评价，从药理活性、药效贡献度以及成分相互作用三个层次建立化学成分组与活性的相关性，并建立基于"组-效"关系的头花蓼质量评价体系。本研究不仅可以解决长期以来头花蓼有效成分不明确、缺乏有效质量控制体系的问题，为头花蓼药材及产品合理的应用提供重要的科学依据，而且可以为基于"有效组分" 的中药新药研制提供基础。

摘要：本课题从苗药头花蓼的活性部位化学成分入手，通过RAW264.7细胞炎症损伤模型为药理评价模型，筛选出70%乙醇提取部位为活性部位。采用UPLC-Q-TOF-MS液质联用法，分析出头花蓼70%乙醇提取部位主要含有酚酸类、黄酮类等25个化合物。利用MCI大孔树脂层析分离，以不同比例甲醇进行梯度洗脱，制备了A~G 7个组分。以抗菌MIC和炎症因子NO、TNF-α、IL-6、PGE2以及体内抗炎实验小鼠耳肿胀法为指标，进一步对7个组分抑菌、抗炎活性进行评价。在化学成分分析和药效实验的基础上，课题还建立了活性部位HPLC特征指纹图谱，并明确了其中8个主要化学成分，可为头花蓼的品种鉴别及质量提升提供依据，已明确了活性部位物质基础。并以活性成分没食子酸、槲皮苷等为指标，建立了头花蓼的多指标含量测定方法。同时，进行了头花蓼单方制剂-热淋清颗粒的药代动力学研究，以及与抗生素-环丙沙星（CIP）的相互作用研究。初步研究结果显示，热淋清颗粒能降低低CIP 的达峰浓度和药时曲线下面积，从而显著降低 CIP 的生物利用度。本项目研究可为“头花蓼”产业链的发展提供基础研究成果。