Wang Jingwen, Wang Dongsheng, Feng Li, Li Xin, Gong Yuanxiang, Wang Zhe, Tan Ninghua, Han Jing
Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China.
Department of Orthopedics, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, PR China.
Phytochemistry. 2023 Apr;208:113603. doi: 10.1016/j.phytochem.2023.113603. Epub 2023 Jan 30.
The traditional Chinese medicine Xanthium sibiricum Patrin ex Widder is used to treat wind-cold headache, nasal congestion, nasal discharge, allergic rhinitis, sinusitis, urticaria, and arthritis. Our previous studies found that sesquiterpene lactones, the main bioactive constituents of X. sibiricum, relieved airway inflammation in an asthma mouse model. To obtain active sesquiterpenes, five undescribed ones, including a pair of eremophilanes and three xanthanolides, together with eight known xanthanolides were isolated from X. sibiricum. Their structures were identified by IR, UV, HR-ESI-MS and NMR spectroscopic data, and their absolute configurations were determined by X-ray crystallographic diffraction analysis and the comparison between their experimental and calculated electronic circular dichroism. All isolated compounds were evaluated for their inhibitory effects on nitric oxide production, and Tnf-α, Il-1β, and Il-6 mRNA expression induced by lipopolysaccharide in the macrophage cell line RAW264.7. Further investigation showed that xanthsibiriolide and 11β-hydroxyl-13-chloro-8-epi-xanthatin exerted their anti-inflammatory effects by inhibiting the PI3K/AKT/mTOR signaling pathway. Analysis of the structure-activity relationships indicated that the α,β-unsaturated lactone ring and the 1,5-epoxide group might be the bioactive groups of xanthanolides, and these results provide a basis for further exploration of sesquiterpene-type lead compounds with anti-inflammatory activity.
传统中药苍耳子用于治疗风寒头痛、鼻塞、流涕、过敏性鼻炎、鼻窦炎、荨麻疹和关节炎。我们之前的研究发现，苍耳子的主要生物活性成分倍半萜内酯可缓解哮喘小鼠模型中的气道炎症。为了获得活性倍半萜，从苍耳子中分离出了5个未描述的化合物，包括一对桉叶烷类化合物和3个苍耳内酯类化合物，以及8个已知的苍耳内酯类化合物。通过红外光谱、紫外光谱、高分辨电喷雾电离质谱和核磁共振光谱数据鉴定了它们的结构，并通过X射线晶体衍射分析以及实验和计算的电子圆二色性比较确定了它们的绝对构型。评估了所有分离化合物对巨噬细胞系RAW264.7中脂多糖诱导的一氧化氮产生以及肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6 mRNA表达的抑制作用。进一步研究表明，苍耳子内酯和11β-羟基-13-氯-8-表-苍耳素通过抑制PI3K/AKT/mTOR信号通路发挥抗炎作用。构效关系分析表明，α,β-不饱和内酯环和1,5-环氧基团可能是苍耳内酯类化合物的生物活性基团，这些结果为进一步探索具有抗炎活性的倍半萜类先导化合物提供了依据。
