云南规模种植石斛中免疫抑制活性成分研究

Autoimmune disease, for example, rheumatoid arthritis, ulcerative colitis, and psoriasis etc. have seriously threatened human health and life because of the complicated precipitating factors and the unclear pathogenesis. Traditionally clinic treatments are mainly immunosuppressors, but leak of efficacy. Additionally, some drugs cause badly side-effect. Although monoclonal antibody drugs are well curative, high specificity of these medications could easily cause the immune tolerance and likely induce the inflection of organism. Moreover, the harsh medication treatment and expensive cost of these drugs together limit the application. Thus, to find new type immunosuppressors with high activity and low toxicity is a significant task for the development of this kind of medicine. Previously, we first found bibenzyls from Dendrobium that was largely cultivated in Yunnan province exhibited strongly immunosuppressive activity and no cytotoxicity. Based on the finding, research on the immunosuppressive components in five species of Dendrobium those are largely cultivated in Yunnan province is planned to carry out in this project. By finishing the project, immunosuppressors with high activity and low toxicity are likely found. At last, the project may support the further innovation in drug candidate development of autoimmune disease.

自身免疫性疾病，如：类风湿性关节炎、溃疡性大肠炎、银屑病等，诱发因素复杂，发病机制尚未阐明，严重威胁人类健康与生活质量。传统临床用药多为免疫抑制剂，但无法根治，且副作用明显。单抗类药物虽疗效显著，但特异性过强容易产生免疫耐受性以及可能诱发机体组织感染，治疗条件苛刻且费用昂贵。因此，发现新型高效低毒免疫抑制剂是这类药物发展的重要方向。基于研究组前期首次发现云南规模种植石斛中联苄类成分具有强免疫抑制活性且无细胞毒性，项目拟开展五种云南规模种植石斛中免疫抑制活性成分的研究，以期发现活性出色的免疫抑制剂，为自身免疫性疾病候选药物研发奠定基础。

自身免疫性疾病，如：类风湿性关节炎、溃疡性大肠炎、银屑病等，诱发因素复杂，发病机制尚未阐明，严重威胁人类健康与生活质量。传统临床用药多为免疫抑制剂，但无法根治，且副作用明显。单抗类药物虽疗效显著，但特异性过强容易产生免疫耐受性以及可能诱发机体组织感染，治疗条件苛刻且费用昂贵。因此，发现新型高效低毒免疫抑制剂是这类药物发展的重要方向。天然药物治疗疾病的历史悠久，天然产物资源丰富，同时天然药物具有成分多样化，药理作用广泛的特点，从中寻找和开发具有免疫抑制活性的先导化合物具有十分显著的优势。石斛属（Dendrobium）植物具有较高的药用价值，其药用历史悠久，《本草纲目》将石斛奉为上品。近年来，石斛多种植物在云南实现规模化种植，对规模种植石斛进行研究，不仅可能得到新型的免疫抑制剂，同时促进对种植资源的深度开发。本项目对云南省德宏州大棚规模种植的铁皮石斛，金钗石斛，齿瓣石斛，鼓槌石斛和兜唇石斛的次生代谢成分进行了系统研究，共分离了192个单体化合物。对所得部分化合物进行的免疫抑制活性测试显示，联苄及菲类衍生物有较好的免疫活性，同时菲类化合物显示出较联苄类化合物更好的免疫抑制活性。上述工作不仅为石斛属植物作为免疫调节药物提供物质基础，同时本次研究所建立的化合物库可以为后续快速研究野生资源，仿生种植资源，林下种植资源和大棚种植资源的差异提供支持。