Agarperoxinols A and B: Two Unprecedented Tricyclic 6/6/7 Rearranged Humulene-Type Sesquiterpenoids That Attenuated the Neuroinflammation in LPS-Stimulated Microglial Models

• Published in: ACS omega Vol. 8; no. 46; pp. 43873 - 43882
• Main Authors: Ma, Chi Thanh, Lee, Sang Bin, Cho, In Ho, Yu, Jae Sik, Huang, Tianqi, Lee, Tae Min, Ly, Tu Loan, Kwon, Sung Won, Park, Jeong Hill, Yang, Hyun Ok
• Format: Journal Article
• Language: English
• Published: American Chemical Society 21.11.2023
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.3c05783

Agarperoxinols A and B (1-2), two naturally occurring humulene-type sesquiterpenoids with an unprecedented tricyclic 6/6/7 ring, were discovered from the agarwood of Aquilaria malaccensis. Their structures were unambiguously determined by various spectroscopic data, experimental ECD calculations, and single-crystal X-ray diffraction analysis. Agarperoxinol B showed significant and dose-dependent neuroinflammatory inhibitory effects on various proinflammatory mediators, including NO, TNF-α, IL-6, and IL-1β, and suppressed iNOS and COX-2 enzymes in LPS-activated microglial cells. A mechanistic study demonstrated that agarperoxinol B remarkably inhibited the phosphorylation of the Akt and JNK signaling pathways. Agarperoxinol B also significantly reduced the expression of the microglial markers Iba-1, COX-2, and TNF-α in the mouse cerebral cortex. Our findings introduce a bioactive compound from natural products that decreases proinflammatory factor production and has application for the treatment of neurodegenerative diseases.