霍山石斛新颖抗炎活性成分的定向发现及其作用机制研究

Due to the serious risk of inflammatory disease, it is urgent that new anti-inflammatory drug with high efficacy and low toxicity should be developed. Dendrobium huoshanense, a well-known orchid plant, has been recorded as a therapeutic agent in traditional Chinese medicine for centuries due to its nutritional values and health benefits. In China, the stems of D. huoshanense were often used as a raw material to make teas, soups and juices to relieve throat inflammation, improve eyesight, nourish stomach and promote body fluid production. Our resent study on the stem of Dendrobium huoshanense showed that its ethanol extracts exhibited significant anti-inflammatory activity. Moreover, it was proved that some novel compounds might be contained in the extracts by UPLC-HRMS analysis, which indicated the presence of novel anti-inflammatory compounds in D. huoshanense. Therefore, the fast and directional isolation of novel anti-inflammatory compounds will be researched under bioactivity and UPLC-HRMS analysis guide in this project. Their structure elucidation, anti-inflammatory activity, and undering anti-inflammatory mechanism will be further investigated to found anti-inflammatory lead compounds. The result of this project will provide a scientific basis for the development of new anti-inflammatory drug and the exploitation of D. huoshanense.

炎症性疾病严重威胁人类健康与生存质量，而临床常用抗炎药多具有毒副作用，因此从中药中定向发现新颖抗炎活性成分用于开发新型高效低毒抗炎药物具有重要意义。霍山石斛作为一味名贵中药，具有极高的药用保健价值，申请者前期研究表明霍山石斛醇提物具有显著抗炎活性，大孔吸附树脂70%和95%乙醇富集段为其活性部位，且UPLC-HRMS分析初步判断活性部位存在新颖化合物。据此，本项目拟运用活性导向与UPLC-HRMS分析紧密相结合的策略对活性组分中新颖化合物进行定向发现，运用多种色谱技术及结构鉴定方法对其进行快速分离与鉴定，运用经典炎症模型对其进行活性评价并优选出活性显著、结构新颖的化合物，最后探讨其对NF-κB、MAPKs、JAK/STAT、PI3K/AKT、Nrf2/OH-1等炎症信号通路的影响，阐明其抗炎作用机制。研究成果将为新型高效低毒抗炎药物的研发奠定基础，为充分利用名贵中药霍山石斛提供科学依据。