蜘蛛香炮制的物质基础和药效变化机理研究

As an important substitute for the European Valeriana officinalis, Valeriana jatamansi Jones (Valerianaceae) has been traditionally used for the treatment of a variety of conditions, especially sleep problems. However, this plant after baking to brown was used to promote digestion in Yi nationality, Gejiu city, Yunnan Province, but the mechanism of material basis and pharmacodynamic change are unclear. Iridoids, the main active components of V. jatamansi, are easily decomposed under high temperature, strong sunlight, and acidic or alkaline conditions, which is theorized as the reason for the pharmacodynamic change between raw V. jatamansi and its processed products. In previous work, we found that, except for baldrinal, the content of unknown constituents increased significantly in the processed products. . This project intends to research the transformation of iridoids during the processing process. The composition and content of iridoids in processed products will be determined, and the characteristic and new constituents emerged during the processing process will be separated. Moreover, the transformation mechanism of chemical constituents before and after the processing process is going to be discussed by a variety of chemical reactions, such as acid hydrolysis, thermolysis, polymerization, and so on. In combination with the sedative-hypnotic and digestive activities, the pharmacodynamic change before and after the processing process will be tested, in order to clarify the synergistic mechanism. This project may provide reasonable instruction for clinical drug use.

蜘蛛香，败酱科缬草属植物，生品主要作为欧缬草代用品用于镇静催眠，而云南省个旧市的彝族民间医生则把蜘蛛香经炒焦后作为健胃消食的一味良药，但其炮制的物质基础及药效变化机理尚不明确。其主要成分环烯醚萜性质活泼，在高温、强光、酸、碱或其他条件下极易降解，推测炒焦过程中环烯醚萜的降解是生品与炒焦制品功效迥异的关键。我们在前期工作中发现，环烯醚萜除降解产生缬草醛外，尚有未知成分含量显著增加。本课题拟以蜘蛛香的主要活性成分环烯醚萜在炮制过程中的转化为研究重点，以蜘蛛香饮片和单体化合物为研究对象，采用炒焦的炮制方法，检测炒焦制品中环烯醚萜类成分的组成和含量，寻找转化产生的新成分和特征差异性成分。并以酸水解、热解、聚合反应等化学方法模拟炮制过程，探讨炮制前后化学成分的转化机理。结合镇静催眠和健胃消食活性检测炮制前后的药效转变，从而阐明炒焦的增效机理，为临床用药提供合理性指导。

蜘蛛香，败酱科缬草属植物，以根茎入药，主要作为欧缬草代用品用于镇静安神，而云南省个旧市的彝族民间医生则将其炒焦后用于健胃消食，推测炒焦过程中其主要成分环烯醚萜的降解是生品与炒焦制品功效迥异的关键。本课题对蜘蛛香生品和炮制品进行了系统的化学成分研究，重点关注环烯醚萜类成分及炮制后转化产生的特征差异性成分，并推导了特征差异性成分的转化机理；结合生品和炮制品的促进消化和镇静安神活性检测，阐明炮制在蜘蛛香药效方面起到的关键作用；另外，本课题还对蜘蛛香生品和炮制品中分离得到的单体化合物进行了NO生成抑制，抗流感病毒和抑制人胶质瘤干细胞活性测试。. 目前，本课题已从蜘蛛香生品的根茎中分离鉴定了118个化合物，结构类型涉及环烯醚萜、倍半萜、木脂素、香豆素和甾体等，并以环烯醚萜类成分为主（85个），包括新化合物43个；从蜘蛛香炮制品中分离鉴定了21个化合物，包括18个特征差异性成分，9个新化合物。动物水平实验证实炮制在蜘蛛香促进消化方面确实起到了关键作用。抗流感病毒活性筛选实验发现，生品中倍半萜88-90对达菲耐药的流感病毒株A/Puerto Rico/8/1934（PR8）具有显著的抑制作用，EC50分别为0.35 ± 0.11，0.31 ± 0.078和0.083 ± 0.017 μg/ml；生品中环烯醚萜48，49和51对达菲耐药的PR8病毒株也具有显著的抑制作用，IC50值分别为0.62 ± 0.21，0.58 ± 0.17和0.088 ± 0.27μg/ml, 同时，化合物48和51对VR1679 (H3N2) 病毒株也具有明显的抑制作用，其IC50分别为0.78 ± 0.27和0.082 ± 0.031 μg/ml。抗肿瘤活性结果显示，生品中化合物20和炮制品中化合物6, 9, 14具有选择性抑制三种人胶质瘤干细胞（GSC-3，GSC-12和GSC-18）活性，IC50值为4.316-13.47 μM。进一步的研究表明，化合物20能够抑制胶质瘤干细胞增殖并诱导其凋亡，还能破坏胶质瘤干细胞集落形成，表明其对胶质瘤干细胞具有体外抗肿瘤活性。本课题为蜘蛛香的临床用药提供了物质基础和科学依据，为抗流感病毒和抗肿瘤药物的研究提供了新的思路。