Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou 510641, China.
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Molecules. 2019 Jul 26;24(15):2726. doi: 10.3390/molecules24152726.
(AP) has been widely used in China for centuries to treat various diseases, and especially to treat inflammation. Diterpenoid lactones are the main anti-inflammatory components of AP. However, systematic chemical composition and biological activities, as well as key pharmacophores, of these diterpenoid lactones from AP have not yet been clearly understood. In this study, 17 diterpenoid lactones, including 2 new compounds, were identified by spectroscopic methods, and most of them attenuated the generation of TNF-α and IL-6 in LPS-induced RAW 274.7 cells examined by ELISA. Pharmacophores of diterpenoid lactones responsible for the anti-inflammatory activities were revealed based on the quantitative structure-activity relationship (QSAR) models. Moreover, new compounds ( and ) exerted anti-inflammatory activity in LPS microinjection-induced zebrafish, which might be correlated with the inhibition of the translocation of NF-κB p65 from cytoplasm to nucleus. Our study provides guidelines for future structure modification and rational drug design of diterpenoid lactones with anti-inflammatory properties in medical chemistry.
（AP）在中国已被广泛应用于治疗各种疾病，尤其是炎症。双萜类内酯是 AP 的主要抗炎成分。然而，AP 中的这些双萜类内酯的系统化学成分组成、生物活性以及关键药效团尚未得到明确的理解。在这项研究中，通过光谱学方法鉴定了 17 种双萜类内酯，其中包括 2 种新化合物，通过 ELISA 检测发现它们大部分能减弱 LPS 诱导的 RAW 274.7 细胞中 TNF-α 和 IL-6 的产生。基于定量构效关系（QSAR）模型揭示了双萜类内酯的药效团，这些药效团负责抗炎活性。此外，新化合物（和）在 LPS 微量注射诱导的斑马鱼中表现出抗炎活性，这可能与抑制 NF-κB p65 从细胞质向细胞核易位有关。本研究为未来医学化学中具有抗炎特性的双萜类内酯的结构修饰和合理药物设计提供了指导。
