基于药物"单-混-谱"模式及TNF-α/NF-κB信号通路探讨土家药血筒抗RA药效物质基础研究

Xiangxibei Tujia traditional medicine Xue Tong (the stem of Kadsura heteroclite (Roxb) Craib) was recorded to possess the function of expelling wind-evil and removing wetness-evil, regulating qi and alleviating pain in terms of traditional Chinese medicine (TCM) for the treatment of wind-dampness, arthralgia-syndrome and various arthritis.In our previous study, we found that total triterpenoids of Kadsura heteroclite has been recognized for its definite effect in anti-inflammatory, analgesia and anti-rheumatoid arthritis. Moreover, plenty of novel structure compounds of triterpene lactones were identified. Thus, an assumption is made that triterpene lactones are the effective substances of anti-rheumatoid arthritis of Xue Tong, producing a synergistic effect in TNF-α/NF-κB signal tranduction pathway in terms of immune inflammatory reaction in RA. Based on this, for effective substances screening we present a new method called "monomer-mixture-spectrum" mode, aiming at the action target, link, and intensity study of triterpene lactones monomers ("monomer"), monomer combinations ("mixture"), and active frations of Xue Tong ("spectrum") in the TNF-α/NF-κB signal pathway. This project will elucidate the anti-rheumatoid arthritis effective substances of Xue Tong, play an important role in revealing the synergisitic machanism of "multi-component, multi-target, multi-link, multi-approach", provide a substance and theory basis for the treatment of wind-dampness and arthragia-syndrome, carry on beneficial exploration on the effective substances and mechanism study of TCM and ethnomedicine.

湘西北土家族药物血筒（异型南五味子藤茎）具有祛风除湿、行气止痛之功效，常用于治疗风湿痹症、关节炎等。我们前期研究发现血筒总三萜具有确切的抗炎镇痛和抗关节炎作用，并分离得到了大量结构新颖的三萜内酯类化合物，因此提出三萜内酯类化合物是血筒抗类风湿性关节炎的药效物质基础，并在抗炎免疫相关TNF-α/NF-κB信号转导通路中发挥协同作用的假设。基于此，我们拟用"单-混-谱"药效物质基础筛选模式，研究血筒三萜内酯类化合物单体（"单"）、单体组合（"混"）和有效部位群（"谱"）在TNF-α/NF-κB信号转导通路中的作用靶点、作用环节和作用强度，对阐明血筒抗类风湿关节炎的药效物质基础，揭示血筒"多成分、多靶点、多环节、多途径"的协同作用机理有重要意义，为该民族药治疗风湿痹症的应用奠定物质理论基础，为中药和民族药药效物质基础和作用机理的研究进行有益的探索和尝试。

湘西北土家族药物血筒（异型南五味子藤茎）具有祛风除湿、行气止痛之功效，常用于治疗风湿痹症、关节炎等。我们前期研究发现血筒总三萜具有确切的抗炎镇痛和抗关节炎作用，本研究采用“单-混-谱”药效物质基础筛选模式，结合动物实验研究了血筒总三萜血筒抗类风湿关节炎的药效物质基础。结果表明，血筒不但具有良好的镇痛抗炎及抗风湿性关节炎的作用，还具有保肝作用。其抗风湿性关节炎作用是通过降低关节肿胀度，显著抑制关节滑膜增生，减少关节翳形成，抑制关节软骨破坏和骨侵蚀，降低大鼠血清TNF-α、IL-1β和IL-6含量从而改善风湿性关节炎的红肿热痛等病理现象起效，研究揭示血筒抗风湿性关节炎的药效物质基础和作用机理；同时还发现了27个新化合物，也进一步发掘了血筒次生代谢产物的多样性，为天然产物提供了更加丰富的内容，为新的生物活性的发现奠定了物质基础。本研究为该民族药治疗风湿痹症的应用奠定物质理论基础，为中药和民族药药效物质基础和作用机理的研究进行有益的探索和尝试，血筒产品的进一步开发将弥补国内外高效、低价抗类风湿性关节炎药物的空缺，为类风湿关节炎患者带来福音，减轻其经济负担，同时将促进民族医药的继承与发展，推动少数民族的经济发展，为社会创造更多的就业机会，创造良好的社会效益。