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Anti-inflammatory Lathyrane Diterpenoids from Euphorbia lathyris

Author:
Zhang, Cui-Yun, Wu, Yan-Li, Zhang, Peng, Chen, Zhuang-Zhuang, Li, Hua, Chen, Li-Xia
Source:
Journal of natural products 2019 v.82 no.4 pp. 756-764
ISSN:
1520-6025
Subject:
Euphorbia lathyris, IKappaB kinase, X-ray diffraction, anti-inflammatory agents, cytotoxicity, diterpenoids, inducible nitric oxide synthase, inhibitory concentration 50, interleukin-1beta, interleukin-6, lipopolysaccharides, macrophages, nitric oxide, protein synthesis, seeds, transcription factor NF-kappa B
Abstract:
Six new lathyrane diterpenoids (1–6) and 10 known analogues (7–16), were separated from the seeds of Euphorbia lathyris. The absolute configuration of 1 was determined by X-ray crystallography, and the C-2′ configuration of 5 was elucidated by comparing experimental and calculated ECD data. These compounds were studied for their inhibition against nitric oxide (NO) generation induced by lipopolysaccharide in RAW264.7 macrophage cells. Compounds 1–3, 7, 9, 11, 13, 14, and 16 displayed inhibitory effects on NO production, with IC₅₀ values of 2.6–26.0 μM. The new compound 1 (IC₅₀ 3.0 ± 1.1 μM), with no obvious cytotoxicity, was selected for further experiments. The production of cytokines such as IL-6 and IL-1β, as well as the protein expression of iNOS, NF-κB, and phosphorylated IκBα, was reduced by 1 dose-dependently. These results suggested that lathyrane diterpenoids may be used as potential anti-inflammatory agents and are worth being further researched.
Agid:
6382390