Germacranolide- and guaianolide-type sesquiterpenoids from Achillea alpina L. reduce insulin resistance in palmitic acid-treated HepG2 cells via inhibition of the NLRP3 inflammasome pathway.
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| Abstract |
Chemical investigation on the aerial part of Achillea alpina L. led to the isolation of twenty sesquiterpenoids. The structures of the undescribed achigermalides A-H were determined by extensive spectroscopic analysis, including NMR, HRESIMS, UV and IR, and their absolute configurations were established by computational electronic circular dichroism (ECD) method. The X-ray crystal structure for 8α-angeloxy-1β,2β:4β,5β-diepoxy-10β-hydroxy-6βH,7αH,11βH-12,6α-guaianolide was reported for the first time. Glucose consumption was analyzed to investigate the effect of all compounds on palmitic acid (PA)-mediated insulin resistance (IR) in HepG2 cells, and achigermalides D-F, desacetylherbohde A, and 4E,10E-3-(2-methylbutyroyloxy)-germacra-4,10(1)-diene-12,6α-olide appreciably enhanced the glucose consumption at low concentrations of 1.56-6.25 μM. Moreover, achigermalide D decreased the expression of IL-1β and the generation of reactive oxygen species (ROS), and also down-regulated the protein levels of TXNIP, NLRP3, caspase-1 and NF-κB in the Western blot analysis, suggesting achigermalide D mediated IR via the suppression of NLRP3 inflammasome pathway.
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| Authors | Gui-Min Xue, Chen-Guang Zhao, Jin-Feng Xue, Kun Du, Jiang-Jing Duan, Hao Pan, Meng Li, Hui Chen, Yan-Jun Sun, Wei-Sheng Feng, Ting Ma, Wen-Da Zhang |
| Journal | Phytochemistry (Phytochemistry) Vol. 202 Pg. 113297 (Oct 2022) ISSN: 1873-3700 [Electronic] England |
| PMID | 35803306 (Publication Type: Journal Article) |
| Copyright | Copyright © 2022 Elsevier Ltd. All rights reserved. |
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