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

• Published in: Phytochemistry (Oxford) Vol. 202; p. 113297
• Main Authors: Xue, Gui-Min, Zhao, Chen-Guang, Xue, Jin-Feng, Du, Kun, Duan, Jiang-Jing, Pan, Hao, Li, Meng, Chen, Hui, Sun, Yan-Jun, Feng, Wei-Sheng, Ma, Ting, Zhang, Wen-Da
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.10.2022; Elsevier
• Subjects: Achillea alpina L; Asteraceae; Biochemistry & Molecular Biology; Germacranolide-type sesquiterpenoid; Glucose consumption; Guaianolide-type sesquiterpenoid; Insulin resistance; Life Sciences & Biomedicine; Plant Sciences; Science & Technology; Germacranolide-type sesquiterpenoid; Guaianolide-type sesquiterpenoid; Insulin resistance; Achillea alpina L; Glucose consumption; Asteraceae; LACTONES; ROOTS; EXTRACTS
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2022.113297

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. [Display omitted]