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Agarperoxinols A and B: Two Unprecedented Tricyclic 6/6/7 Rearranged Humulene-Type Sesquiterpenoids That Attenuated
Chi Thanh Ma1,2, Sang Bin Lee2, In Ho Cho3
1Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, 41-43 Dinh Tien Hoang Street, Dist. 1, Ho Chi Minh City 700000, Vietnam.
Abstract:
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.
