Limonoids from the seeds of Swietenia macrophylla with inhibitory activity against dengue virus 2.

Fractionation of an ethanol-soluble extract of the seeds of Swietenia macrophylla yielded six new limonoids, swielimonoids A-F (1-6), along with 20 known compounds. Compounds 1 and 2, mexicanolide-type limonoids, were assigned with an α,ß-unsaturated δ-lactone moiety (ring D) and a C═C bond between C-8 and C-30. Compounds 3-6 could be categorized as highly oxygenated phragmalin-type limonoids. The structures of these new compounds were elucidated through the interpretation of spectroscopic data. The antidengue virus 2 activities of the isolated components from S. macrophylla were investigated, and of 12 compounds subjected to bioassay, compounds 2 and 7-10 were found to show inhibitory activity in the range 3.5 to 12.5 µM. Among these, the new limonoid 2 exhibited significant antiviral activity (EC50 = 7.2 ± 1.33 µM) with a selectivity index (CC50/EC50) value of >27.7.

Suppression of ERK/NF-κB Activation Is Associated With Amentoflavone-Inhibited Osteosarcoma Progression In Vivo.

BACKGROUND/AIM: Amentoflavone has been implicated in reducing the metastatic potential of osteosarcoma (OS) cells in vitro. The aim of the present study was to verify the antitumoral efficacy and the potential mechanism of amentoflavone osteosarcoma progression inhibition in vivo. MATERIALS AND METHODS: A U-2 OS osteosarcoma xenograft mouse model was used in this study. Mice were treated with a vehicle control or amentoflavone (100 mg/kg/day) for 15 days. Tumor growth, signal transduction, and expression of tumor progression-associated proteins were evaluated using a digital caliper, bioluminescence imaging (BLI), animal computed tomography (CT), and ex vivo western blotting assay. RESULTS: Amentoflavone significantly inhibits tumor growth and reduces protein levels of phospho-extracellular signal-regulated kinase (P-ERK), nuclear factor-kappaB (NF-κB) p65 (Ser536), vascular endothelial growth factor (VEGF), matrix metallopeptidase 9 (MMP-9), X-linked inhibitor of apoptosis protein (XIAP), and cyclin-D1 in osteosarcoma in vivo. CONCLUSION: The inhibition of ERK/NF-κB activation is associated with amentoflavone-inhibited osteosarcoma progression in vivo.

The effects of acute stress-induced sleep disturbance on acoustic trauma-induced tinnitus in rats.

Chronic tinnitus is a debilitating condition and often accompanied by anxiety, depression, and sleep disturbance. It has been suggested that sleep disturbance, such as insomnia, may be a risk factor/predictor for tinnitus-related distress and the two conditions may share common neurobiological mechanisms. This study investigated whether acute stress-induced sleep disturbance could increase the susceptibility to acoustic trauma-induced tinnitus in rats. The animals were exposed to unilateral acoustic trauma 24 h before sleep disturbance being induced using the cage exchange method. Tinnitus perception was assessed behaviourally using a conditioned lick suppression paradigm 3 weeks after the acoustic trauma. Changes in the orexin system in the hypothalamus, which plays an important role in maintaining long-lasting arousal, were also examined using immunohistochemistry. Cage exchange resulted in a significant reduction in the number of sleep episodes and acoustic trauma-induced tinnitus with acoustic features similar to a 32 kHz tone at 100 dB. However, sleep disturbance did not exacerbate the perception of tinnitus in rats. Neither tinnitus alone nor tinnitus plus sleep disturbance altered the number of orexin-expressing neurons. The results suggest that acute sleep disturbance does not cause long-term changes in the number of orexin neurons and does not change the perception of tinnitus induced by acoustic trauma in rats.