Introduction: Sulfur compounds isolated from garlic exert anti-inflammatory properties. We recently isolated thiacremonone, a novel sulfur compound from garlic. Here, we investigated the anti-inflammatory and arthritis properties of thiacremonone through inhibition of NF-κB since NF-κB is known to be a target molecule of sulfur compounds and an implicated transcription factor regulating inflammatory response genes. Methods: The anti-inflammatory and arthritis effects of thiacremone in in vivo were investigated in 12-O-tetradecanoylphorbol-13-acetate-induced ear edema, carrageenan and mycobacterium butyricum-induced inflammatory and arthritis models. Lipopolysaccharide-induced nitric oxide (NO) production was determined by Griess method. The DNA binding activity of NF-κB was investigated by electrophoretic mobility shift assay. NF-κB and inducible nitric oxide synthetase (iNOS) transcriptional activity was determined by luciferase assay. Expression of iNOS and cyclooxygenase-2 (COX-2) was determined by western blot. Results: The results showed that topical application of thiacremonone (1 or 2 μg/ear) suppressed the 12-O-tetradecanoylphorbol-13-acetate-induced (1 μg/ear) ear edema. Thiacremonone (1-10 mg/kg) administered directly into the plantar surface of hind paw also suppressed the carrageenan (1.5 mg/paw) and mycobacterium butyricum (2 mg/paw)-induced inflammatory and arthritic responses as well as expression of iNOS and COX-2, in addition to NF-κB DNA-binding activity. In further in vitro study, thiacremonone (2.5-10 μg/ml) inhibited lipopolysaccharide (LPS, 1 μg/ml)-induced nitric oxide (NO) production, and NF-κB transcriptional and DNA binding activity in a dose dependent manner. The inhibition of NO by thiacremonone was consistent with the inhibitory effect on LPS-induced inducible nitric oxide synthase (iNOS) and COX-2 expression, as well as iNOS transcriptional activity. Moreover, thiacremonone inhibited LPS-induced p50 and p65 nuclear translocation, resulting in an inhibition of the DNA binding activity of the NF-κB. These inhibitory effects on NF-κB activity and NO generation were suppressed by reducing agents dithiothreitol (DTT) and glutathione, and were abrogated in p50 (C62S)-mutant cells, suggesting that the sulfhydryl group of NF-κB molecules may be a target of thiacremonone. Conclusions: The present results suggested that thiacremonone exerted its anti-inflammatory and anti-arthritic properties through the inhibition of NF-κB activation via interaction with the sulfhydryl group of NF-κB molecules, and thus could be a useful agent for the treatment of inflammatory and arthritic diseases.

This study evaluated changes in ginsenoside compositions and antioxidant activities in hydroponic-cultured ginseng roots (HGR) and leaves (HGL) with heating temperature. Heat treatment was performed at temperatures of 90°C, 110°C, 130°C, and 150°C for 2 hours. The ginsenoside content varied significantly with heating temperature. The levels of ginsenosides Rg1 and Re in HGR decreased with increasing heating temperature. Ginsenosides F2, F4, Rk3, Rh4, Rg3 (S form), Rg3 (R form), Rk1, and Rg5, which were absent in the raw ginseng, were formed after heat treatment. The levels of ginsenosides Rg1, Re, Rf, and Rb1 in HGL decreased with increasing heating temperature. Conversely, ginsenosides Rk3, Rh4, Rg3 (R form), Rk1, and Rg5 increased with increasing heating temperature. In addition, ginsenoside contents of heated HGL were slightly higher than those of HGR. The highest extraction yield was 14.39% at 130°C, whereas the lowest value was 10.30% at 150°C. After heating, polyphenol contents of HGR and HGL increased from 0.43 mg gallic acid equivalent/g (mg GAE eq/g) and 0.74 mg GAE eq/g to 6.16 mg GAE eq/g and 2.86 mg GAE eq/g, respectively. Antioxidant activities of HGR and HGL, measured by 1,1-diphenyl-2-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging ability, increased with increasing heating temperature. These results may aid in improving the biological activity and quality of ginseng subjected to heat treatments.

Background: Alzheimer’s disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) fibrils within the brain and activation of astrocytes and microglial cells. In this study, we examined anti-inflammatory and anti-amyloidogenic effects of 2,4-bis(p-hydroxyphenyl)-2-butenal (HPB242), an anti-inflammatory compound produced by the tyrosine-fructose Maillard reaction. Methods: 12-month-old Tg2576 mice were treated with HPB242 (5 mg/kg) for 1 month and then cognitive function was assessed by the Morris water maze test and passive avoidance test. In addition, western blot analysis, Gel electromobility shift assay, immunostaining, immunofluorescence staining, ELISA and enzyme activity assays were used to examine the degree of Aβ deposition in the brains of Tg2576 mice. The Morris water maze task was analyzed using two-way ANOVA with repeated measures. Otherwise were analyzed by one-way ANOVA followed by Dunnett’s post hoc test. Results: Treatment of HPB242 (5 mg/kg for 1 month) significantly attenuated cognitive impairments in Tg2576 transgenic mice. HPB242 also prevented amyloidogenesis in Tg2576 transgenic mice brains. This can be evidenced by Aβ accumulation, BACE1, APP and C99 expression and β-secretase activity. In addition, HPB242 suppresses the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as activation of astrocytes and microglial cells. Furthermore, activation of nuclear factor-kappaB (NF-κB) and signal transducer and activator of transcription 1/3 (STAT1/3) in the brain was potently inhibited by HPB242. Conclusions: Thus, these results suggest that HPB242 might be useful to intervene in development or progression of neurodegeneration in AD through its anti-inflammatory and anti-amyloidogenic effects.