基于体内动态效应的蒙药森登-4治疗风湿性关节炎的药效物质基础研究

Compound studies on potential basis is the core research areas of the Mongolian medicine . Mongolian compound Sendeng -4 is the traditional formula which commonly used for acetanilide detumescence on the Mongolian medicine clinical. It is also the Mongolian medicine classical prescriptions in the clinical treatment of rheumatoid arthritis , and it is included in the "People's Republic of China Ministry of Health Drug Standards (Mongolian Volume)." This subject has completed the effective parts of preparation technology, the main chemical composition separation,analysis, quality control and related pharmacology experimental research, a preliminary study on the fingerprint - effect relationship in vitro and preliminarily determined its active components of the rheumatoid arthritis resistance on the basis of the clinical curative effect treatment of rheumatoid arthritis. This project intends to develop the HPLC - MS on the research of Mongolian compound Sendeng -4’s effective parts dynamic serum chemistry in vivo, dynamic metabolic drugs chemical effect in biological and chemical process and the chemical composition in vitro mapping study. We will screen and evaluate the pharmacodynamics associated with rheumatoid arthritis of the effective ingredient group . And the subject also want to interprete the Mongolian compound Sendeng -4’s efficacy material base for rheumatoid arthritis from multiple perspectives , establish the combination Mongolian compound research model of chemical composition - in effect - efficacy validation , improve the efficiency of Mongolian compound material basic research , provide a scientific basis for for the compound further development and promote Mongolian to be modernization and standardization.

复方药效物质基础研究是蒙医药研究领域的核心内容。蒙药复方森登-4是蒙医临床上常用的消肿止痛传统配方，亦为蒙医临床治疗风湿性关节炎的经典方剂，被收载于《中华人民共和国卫生部药品标准(蒙药分册)》。本课题在森登-4治疗风湿性关节炎临床疗效确切的基础上，已完成其有效部位制备工艺、主要化学成分的分离、分析、质量控制以及相关药理学实验研究，并进行体外指纹图谱-药效关系初步研究，初步确定其抗风湿关节炎的有效成分群。本项目拟采用HPLC-MS开展森登-4有效部位体内动态血清药物化学、动态代谢药物化学的生物和化学效应变化过程及体外化学成分图谱研究；对有效组分群进行与风湿性关节炎相关的药效学筛选与评价，多角度阐释森登-4用于风湿性关节炎的药效物质基础，建立化学成分-体内效应-药效验证相结合的蒙药复方研究模式，提高蒙药复方物质基础研究效率，为该复方深入开发提供科学依据；促进蒙药现代化、标准化进程。

复方药效物质基础研究是蒙医药研究领域的核心内容。蒙药复方森登-4是蒙医临床上常用的消肿止痛传统配方，亦为蒙医临床治疗风湿性关节炎的经典方剂，被收载于《中华人民共和国卫生部药品标准(蒙药分册)》。. 本课题在森登-4治疗风湿性关节炎临床疗效确切的基础上，采用HPLC-MS开展森登-4体内动态血清药物化学、动态代谢药物化学的生物和化学效应变化过程及体内外化学成分图谱研究。通过对森登-4有效组分群与风湿性关节炎相关靶点进行药效学筛选与评价，多角度阐释森登-4治疗风湿性关节炎的药效物质基础。. 本课题建立了胶原Ⅱ诱导的风湿性关节炎大鼠模型，确定了生物样本的处理方法，通过不同配伍特征图谱的谱效关系研究辨识了森登-4治疗风湿性关节的体内直接效应成分为黄酮类（杨梅素、二氢杨梅素、儿茶素、表儿茶素、芦丁）和萜类（栀子苷、京尼平龙胆二糖苷）。测定了给予森登-4后正常大鼠和风湿性关节炎模型大鼠血清、尿液中总黄酮和总萜的含量，以及血清和关节液中的栀子苷、京尼平龙胆二糖苷、杨梅素、二氢杨梅素的含量，并比较其药代动力学差异，明确了目标活性成分在病变关节中具有选择性富集作用。明确了森登-4目标组分的体内分布及代谢规律。通过分子对接模拟预测蒙药森登-4治疗风湿性关节炎潜在的有效成分为杨梅素、二氢杨梅素等。通过敲入-敲出制备得到含不同浓度目标组分的森登-4样品，以IL-6、IL-1β、TNFα、PGE2、iNOs含量为指标对其进行药效学评价，辨识了杨梅素、二氢杨梅素、表儿茶素、原花青素A2是森登-4抗炎活性的关键药效成分，四个目标组分与森登-4抗炎活性成剂量依赖关系，且在复方中发挥的抗炎作用大于单独作用时的抗炎作用。.本课题建立了从化学成分提取分离-体内效应物质动态过程跟踪—分子对接模拟预测—药效学评价确认药效物质群相结合的整体研究模式，为森登-4深入开发提供科学依据，提高了蒙药复方物质基础研究效率，促进了蒙药现代化、标准化进程。