基于花生四烯酸代谢网络的沙枣花抗炎活性成分及作用机制研究

Arachidonic acid (AA) and its metabolites play an important role in the generation and development of inflammation, and its metabolic network provides a number of important targets for the development of anti-inflammatory drugs. The flowers of Elaeagnus angustifolia L., one of the Uighur Medicine, were used in the treatment of chronic bronchitis and arthritis. In our preliminary study, the ethanol extract of flowers of E. angustifolia showed strong inhibitory activity against lipopolysaccharide-induced nitric oxide and prostaglandin E2 production in RAW 264.7 cells. However, to date, the effective substances of flowers of E. angustifolia for the treatment of inflammation related disease and their action mechanism remain unknown. Based on the traditional use of the flowers of E. angustifolia and our preliminary study, bioassay guided isolation and identification of anti-inflammatory compounds will be conducted in this project, two key enzymes in AA metabolic network, cyclooxygenase (COX) and lipoxygenase (LO), will be the targets. The action mechanism of anti-inflammatory of the isolates will be evaluated. Overall, the purposes of this study are discovering anti-inflammatory lead compounds and exploring the effective substances of the flowers of E. angustifolia, which lay the solid foundation of the development of new drugs of Traditional Chinese Medicine and Uighur Medicine.

花生四烯酸及其代谢产物在炎症的产生和发展中发挥着重要作用，其代谢网络为抗炎药物的开发提供了多个重要靶标。植物沙枣（Elaeagnus angustifolia L.）花为维吾尔医常用药材，用于治疗慢性支气管炎、缓解关节疼痛等疾病，在我们的前期研究中发现沙枣花乙醇提取物对脂多糖诱导巨噬细胞NO和PGE2释放表现出很强的抑制作用。然而，沙枣花的治疗炎症相关疾病的药效物质及其作用机制至今尚不明确。本项目基于沙枣花在炎症相关疾病方面的传统药用以及我们的前期研究结果，以花生四烯酸代谢网络中的两个关键酶：环氧酶（COX）和脂氧酶（LO）为靶标，运用活性导向与现代色谱技术相结合的方法，快速发现沙枣花中具有抗炎活性的化合物，并研究其抗炎作用机制。通过本项目的研究，可以发现抗炎新药的先导化合物，同时可以阐明沙枣花治疗炎症相关疾病的药效物质基础，并为从传统药用植物开发中药、民族药新药奠定坚实的基础。