Guaianolides from Achillea millefolium L. and their anti-inflammatory activity.

Seven previously undescribed guaianolides, millefolactons A-G, and three known analogues, millefoliumins A-C, were isolated from the whole plant of Achillea millefolium L. growing in Xinjiang, China. Their structures were elucidated using the HR-ESI-MS and NMR data analyses. The absolute configurations of millefolactons A-G were determined by single-crystal X-ray crystallography, ECD data analysis, and quantum-chemical ECD calculations. Millefolactons A-E are rare 3-oxa-guaianolides. Millefolacton C, millefolacton E, millefoliumin A and millefoliumin B exhibited enzymatic inhibition of 15-LOX. Molecular docking simulations were conducted to visualize interactions between the four active compounds and 15-LOX and determine binding mechanisms. Moreover, a LPS-induced BV2 cell model was used to further investigate the anti-inflammatory mechanism of millefolacton C. As a result, millefolacton C significantly inhibited NO release, repressed levels of pro-inflammatory cytokines including TNF-α, IL-18, PGE2 and IL-6, and inhibited the protein expression of iNOS and COX2 proteins. In addition, millefolacton C could potently decreased the expression of NLRP3, ASC, and IL-1β proteins in LPS-stimulated BV2 cells. These results indicate that the 3-oxa-guaianolides from A. millefolium L. offer great potential as leads for anti-inflammatory drug development. Copyright © 2023 Elsevier Ltd. All rights reserved.

Citation

Hongliang Li, Liu Liu, Guanghui Gou, Xuelei Xin, Jun Li, Haji Akber Aisa. Guaianolides from Achillea millefolium L. and their anti-inflammatory activity. Phytochemistry. 2023 Jun;210:113647

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PMID: 36963706

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