RESUMEN
Seven unknown compounds 1-7, including four sesquiterpenoids, one azulene-type, one indene-type, and one rare hexanorcucurbitacin, together with eleven knowns ones (8-16), were isolated from the agarwood chips of Aquilaria malaccensis. The structures of the isolated compounds were elucidated by extensive spectroscopic methods such as mass spectrometry, UV, IR, NMR spectroscopy. The precise stereo-chemical configurations of new compounds were determined by calculated ECD spectra data, as well as a single-crystal X-ray diffraction analysis. The isolated compounds 1-7 were evaluated by estimating the levels of nitric oxide (NO), TNF-α, and the expression of enzyme iNOS, and COX-2. Among them, a rare hexanortriterpenoid (7) derived from a cucurbitane-type triterpenoid showed the significantly attenuated neuro-inflammatory effects via the STAT1/AKT/MAPK/NLRP3 signaling pathway on the mechanistic studies.
RESUMEN
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-1ß, 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.
RESUMEN
Nine undescribed sesquiterpenes, which include five guaiane and four humulene-type, were isolated from the agarwood of Aquilaria malaccensis. The structures of these undescribed sesquiterpenes were elucidated by spectroscopic methods including UV, HRESI-MS, 1D and 2D-NMR, ECD, and X-ray diffraction (Cu Kα). The isolated compounds were tested for their inhibitory effect against LPS-induced NO production in RAW 264.7 cells. In particular, one sesquiterpene (1α,7α-dihydroxy-8oxo-4αH,5αH-guaia-9(10),11(13)-dien-12-oate) showed significant inhibition of NO production in LPS-stimulated macrophage RAW 264.7 cells with an IC50 value of 18.8 µM.