Sesquiterpene lactones from Inula falconeri, a plant endemic to the Himalayas, as potential anti-inflammatory agents

• Published in: European journal of medicinal chemistry 2011-11, Vol.46 (11), p.5408-5415
• Main Authors: Cheng, Xiangrong, Zeng, Qi, Ren, Jie, Qin, Jiangjiang, Zhang, Shoude, Shen, Yunheng, Zhu, Jiaxian, Zhang, Fei, Chang, Ruijie, Zhu, Yan, Zhang, Weidong, Jin, Huizi
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammation; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Cell Line; Compositae family; General pharmacology; Inula - chemistry; Inula - growth & development; Inula falconeri; Lactones - chemistry; Lactones - isolation & purification; Lactones - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Medical sciences; Mice; Nitric oxide; Nitric Oxide - biosynthesis; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; RAW264.7 macrophage; Sesquiterpene lactone; Sesquiterpenes - chemistry; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2011.08.047

A phytochemical investigation of Inula falconeri, a plant endemic to the Himalayas, afforded 10 new sesquiterpenoids and 26 known sesquiterpene lactones, including those bearing guaiane, pseudoguaiane, xanthane, eudesmane, germacrane, rare secocaryophyllane, chromolaevane, and carabrane frameworks. The structures were elucidated via spectroscopic analysis and compared with data from literature. All the isolates were assessed for their inhibitory effects against LPS-induced nitric oxide production in RAW264.7 macrophages. Compounds 4, 11, 24, and 31 showed stronger inhibitory activities than the positive control with IC50 values of 0.13, 0.07, 0.11, and 0.11 μM, respectively. These studies also led to a better understanding of the structure-activity relationships for the sesquiterpene lactone family of compounds. Ten new and 26 known sesquiterpenoids were isolated from Inula falconeri, a plant endemic to the Himalayas, with inhibitory effects against LPS-induced nitric oxide production in RAW264.7 macrophages. [Display omitted] ▸ A series of sesquiterpene lactones were isolated from I. falconeri. ▸ Structures mainly belonged to guaiane, pseudoguaiane, and xanthane skeletons. ▸ 4, 11, 24, and 31 presented more potent nitric oxide inhibition than aminoguanidine. ▸ A preliminary structure-activity relationship was established.