Natural anti-neuroinflammatory inhibitors in vitro and in vivo from Aglaia odorata.
In: Bioorganic Chemistry, Jg. 147 (2024-06-01), S. N.PAG
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Zugriff:
[Display omitted] • Seven undescribed compounds were identified from Aglaia odorata. • The cis – trans isomerization equilibrium of tertiary amides was conducted. • Compounds 2–6, 8, 10, and 12 inhibited NO production at the nanomolar concentration. • The anti-neuroinflammatory effects of rocaglaol (12) were investigated in vivo. Fifty compounds including seven undescribed (1 , 13 , 18 – 20 , 30 , 31) and forty-three known (2 – 12 , 14 – 17 , 21 – 29 , 32 – 50) ones were isolated from the extract of the twigs and leaves of Aglaia odorata with anti-neuroinflammatory activities. Their structures were determined by a combination of spectral analysis and calculated spectra (ECD and NMR). Among them, compounds 13 – 25 were found to possess tertiary amide bonds, with compounds 16 , 17 , and 19 – 21 existing detectable cis / trans mixtures in 1H NMR spectrum measured in CDCl 3. Specifically, the analysis of the cis – trans isomerization equilibrium of tertiary amides in compounds 19 – 24 was conducted using NMR spectroscopy and quantum chemical calculations. Bioactivity evaluation showed that the cyclopenta[ b ]benzofuran derivatives (2 – 6 , 8 , 10 , 12) could inhibit nitric oxide production at the nanomolar concentration (IC 50 values ranging from 2 to 100 nM) in lipopolysaccharide-induced BV-2 cells, which were 413–20670 times greater than that of the positive drug (minocycline, IC 50 = 41.34 μM). The cyclopenta[ bc ]benzopyran derivatives (13 – 16), diterpenoids (30 – 35), lignan (40), and flavonoids (45 , 47 , 49 , 50) also demonstrated significant inhibitory activities with IC 50 values ranging from 1.74 to 38.44 μM. Furthermore, the in vivo anti-neuroinflammatory effect of rocaglaol (12) was evaluated via immunofluorescence, qRT-PCR, and western blot assays in the LPS-treated mice model. The results showed that rocaglaol (12) attenuated the activation of microglia and decreased the mRNA expression of iNOS, TNF- α , IL-1 β , and IL-6 in the cortex and hippocampus of mice. The mechanistic study suggested that rocaglaol might inhibit the activation of the NF-κB signaling pathway to relieve the neuroinflammatory response. [ABSTRACT FROM AUTHOR]
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Natural anti-neuroinflammatory inhibitors in vitro and in vivo from Aglaia odorata.
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Autor/in / Beteiligte Person: | Yin, Qianqian ; Chen, Gang ; Mu, Danyang ; Yang, Yuxin ; Hao, Jinle ; Lin, Bin ; Zhou, Di ; Hou, Yue ; Li, Ning |
Zeitschrift: | Bioorganic Chemistry, Jg. 147 (2024-06-01), S. N.PAG |
Veröffentlichung: | 2024 |
Medientyp: | academicJournal |
ISSN: | 0045-2068 (print) |
DOI: | 10.1016/j.bioorg.2024.107335 |
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