疼痛与炎症一直以来为医学界所关注。研究表明内源性大麻素参与建立体内镇痛体系，能够在外周组织和中枢神经系统中显著地缓解疼痛发生。PEA是一种重要的镇痛抗炎作用的内源性大麻素，但它在许多组织中易被NAAA 酶水解代谢而阻碍了其对抗外周炎症的功能。因此抑制NAAA活性，使PEA维持正常生理水平是治疗外周疼痛与炎症的有效途径之一。本项目旨在UPLC-QTOF-HRMS、NMR等指导下，通过活性跟踪方法从雪莲内生真菌TPF15和TPF37发酵液中快速发现结构新颖且具有镇痛抗炎作用的次级代谢产物；并采用化学-表观遗传学方法，通过在培养液中加入酶抑制剂，获得更多新颖的活性代谢产物；通过对得到的单体化合物活性测试结果探讨其构效关系，进而从雪莲内生真菌中发现NAAA抑制剂。本项目不仅在阐明2株内生真菌中NAAA抑制剂的快速发现上具有重要科学意义，而且可为镇痛抗炎药的研发提供新型物质基础。

Some researches indicate that endogenous cannobinoids participate in establishing analgesia tone, and they can ease pain in the peripheral tissue and cetral nervous system. PEA is an important endogenous cannobinoid for analgesia and anti-inflammatory effects. However, it is hydrolyzed easily by NAAA in many tissues and its anti-inflammatory functions are hindered simultaneously. Thus, if the activity of NAAA is inhibited, it should be one of the efficient way for analgesia and anti-inflammatory effects to keep PEA's normal level. This proposal is to discover the novel, analgesia and anti-inflammatory secondary metabolites quickly from endophytic fungi （TPF15 and TPF26）of Saussurea medusa, using bio-guided methods by UPLC-QTOF-HRMS and NMR analysis. A chemical epigenetics approach is applied to aquire more bioactive novel metabolites by adding the inhibitor of enzyme to culture media. The SAR will be discussed among the active compounds in order to discover the potent inhibitors of NAAA. This proposal is not only significant for discovering the inhibitors of NAAA from two strains of fungi, but also the basis for developing the analgesia and anti-inflammatory drugs.