Background: Cinnamon bark is one of the most popular herbal ingredients in traditional oriental medicine and possesses diverse pharmacological activities including anti-bacterial, anti-viral, and anti-cancer properties. The goal of this study is to investigate the in vivo and in vitro inhibitory effect of cinnamon water extract (CWE) on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and its underlying intracellular mechanisms. Methods: CWE was orally administrated to mice for 6 days prior to intraperitoneal injection of LPS. Serum levels of TNF-α and interleukin (IL)-6 were determined 1 hour after LPS stimulation. Peritoneal macrophages from thioglycollate-injected mice were isolated and assayed for viability, cytokine expression and signaling molecules upon LPS stimulation. CWE was further fractioned according to molecular size, and the levels of total polyphenols and biological activities of each fraction were measured. Results: The oral administration of CWE to mice significantly decreased the serum levels of TNF-α and IL-6. CWE treatment in vitro decreased the mRNA expression of TNF-α. CWE blocked the LPS-induced degradation of IκBα as well as the activation of JNK, p38 and ERK1/2. Furthermore, size-based fractionation of CWE showed that the observed inhibitory effect of CWE in vitro occurred in the fraction containing the highest level of total polyphenols. Conclusions: Treatment with CWE decreased LPS-induced TNF-α in serum. In vitro inhibition of TNF-α gene by CWE may occur via the modulation of IκBα degradation and JNK, p38, and ERK1/2 activation. Our results also indicate that the observed anti-inflammatory action of CWE may originate from the presence of polyphenols.

Buckwheat sprouts have been widely consumed all around world due to their great abundance of bioactive compounds. In this study, the anti‐inflammatory effects of flavonoid‐rich common buckwheat sprout (CBS) and tartary buckwheat sprout (TBS) extracts were evaluated in lipopolysaccharide‐ (LPS‐) stimulated RAW 264.7 murine macrophages and primary peritoneal macrophages from male BALB/c mice. Based on the reversed‐phase HPLC analysis, the major flavonoids in CBS were determined to be C‐glycosylflavones (orientin, isoorientin, vitexin, and isovitexin), quercetin‐3‐O‐robinobioside, and rutin, whereas TBS contained only high amounts of rutin. The TBS extract exhibited higher inhibitory activity as assessed by the production of proinflammatory mediators such as nitric oxide and cytokines including tumor necrosis factor‐α, interleukin‐ (IL‐) 6, and IL‐12 in LPS‐stimulated RAW 264.7 macrophages than CBS extract. In addition, TBS extract suppressed nuclear factor‐kappa B activation by preventing inhibitor kappa B‐alpha degradation and mitogen‐activated protein kinase phosphorylation in LPS‐stimulated RAW 264.7 macrophages. Moreover, the TBS extract markedly reduced LPS‐induced cytokine production in peritoneal macrophages. Taken together, these findings suggest that TBS extract can be a potential source of anti‐inflammatory agents that may influence macrophage‐mediated inflammatory disorders.

Until recently, fermentation was the only processing used to improve the functionality of wheat germ. The release of 2,6-dimethoxy-1,4-benzoquinone (DMBQ) from hydroquinone glycosides during the fermentation process is considered a marker of quality control. Here, we treated wheat germ extract with citric acid (CWG) to release DMBQ and examined the anti-inflammatory activity of this extract using a lipopolysaccharide-activated macrophage model. Treatment of wheat germ with citric acid resulted in detectable release of DMBQ but reduced total phenolic and total flavonoid contents compared with untreated wheat germ extract (UWG). CWG inhibited secretion of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-12 and the synthesis of cyclooxygenase-2, while UWG only decreased IL-12 production. CWG and UWG induced high levels of anti-inflammatory IL-10 and heme oxygenase-1. CWG specifically inhibited phosphorylation of NF-κB p65 and p38 kinase at 15 min after LPS stimulation. Our study showed that citric acid treatment enhanced the anti-inflammatory activity of wheat germ extract.

Sakuranetin is flavonoid phytoalexin that serves as a plant antibiotic and exists in Prunus and several other plant species. Recently, we identified the anti‐inflammatory effect of Prunus yedoensis and found that there were few studies on the potential anti‐inflammatory activity of sakuranetin, one of the main constituents of Prunus yedoensis. Here, we isolated peritoneal macrophages from thioglycollate‐injected mice and examined whether sakuranetin affected the response of the macrophages in response to lipopolysaccharide (LPS) plus interferon‐ (IFN‐) γ or LPS only. Sakuranetin suppressed the synthesis of iNOS and COX2 in LPS/IFN‐γ stimulated cells and the secretion of TNF‐α, IL‐6, and IL‐12 in LPS stimulated cells. The surface expression of the costimulatory molecules, CD86 and CD40, was also decreased. Among the LPS‐induced signaling molecules, STAT1, JNK, and p38 phosphorylation was attenuated. These findings are evidence that sakuranetin acts as anti‐inflammatory flavonoid and further study is required to evaluate its in vivo efficacy.

Water soluble cinnamon extract has been shown to increase insulin sensitivity and modulate macrophage activation, a desirable trait for the management of obesity or atherosclerosis. Our present study investigated whether cinnamon water extract (CWE) may influence the differentiation of monocytes into macrophages and the activity of macrophage scavenger receptors, commonly observed in atherosclerotic lesions.