Suppression of IL‐8 Release by Sweet Olive Ethanolic Extract and Compounds in WiDr Colon Adenocarcinoma Cells

Oxidative stress can stimulate the secretion of pro‐inflammatory cytokines. Interleukin‐8 (IL‐8) has been implicated in the pathogenesis of inflammatory bowel disease and the metastatic spread of colorectal cancer. The flowers of Osmanthus fragrans (sweet olive) are used to alleviate dysentery with blood in the bowel, as well as stomach ache and diarrhea. However, the evidence of their therapeutic effects on these symptoms remains unclear. In the present study, the protective effects of sweet olive flower ethanolic extract (OFE) against oxidative stress in WiDr cells was assessed by evaluating its 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) free radical scavenging activity. In addition, cellular IL‐8 secretion was evaluated. Notably, high‐performance liquid chromatography showed verbascoside to be the primary constituent in OFE; it exhibited a DPPH scavenging activity with an IC₅₀ of 8.23 μg/mL. Moreover, OFE (1 to 100 μg/mL) showed a potent, dose‐dependent inhibitory effect on H₂O₂‐induced IL‐8 secretion in WiDr cells. Nine compounds were isolated from OFE based on a protective effect‐guided purification process. Of these compounds, 5 phenolic compounds—verbascoside, phillygenin, tyrosol, methyl 4‐hydroxycinnamate, and eutigoside A—reduced IL‐8 secretion at 10 μg/mL treatment concentrations. Further analysis showed that the anti‐inflammatory effects of OFE likely occurred via nuclear factor‐κB pathway inhibition, which attenuates IL‐8 secretion in cells. Collectively, these data suggest that OFE could be developed as an agent that suppresses IL‐8 secretion to treat chronic inflammatory diseases.     

Ginger Extract Suppresses Inflammatory Response and Maintains Barrier Function in Human Colonic Epithelial Caco‐2 Cells Exposed to Inflammatory Mediators

The beneficial effects of ginger in the management of gastrointestinal disturbances have been reported. In this study, the anti‐inflammatory potential of ginger extract was assessed in a cellular model of gut inflammation. In addition, the effects of ginger extract and its major active compounds on intestinal barrier function were evaluated. The response of Caco‐2 cells following exposure to a mixture of inflammatory mediators [interleukin [IL]‐1β, 25 ng/mL; lipopolysaccharides [LPS], 10 ng/mL; tumor necrosis factor [TNF]‐α, 50 ng/mL; and interferon [INF]‐γ, 50 ng/mL] were assessed by measuring the levels of secreted IL‐6 and IL‐8. In addition, the mRNA levels of cyclooxygenase‐2 and inducible nitric oxide synthase were measured. Moreover, the degree of nuclear factor (NF)‐κB inhibition was examined, and the intestinal barrier function was determined by measuring the transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)‐dextran transfer. It was observed that ginger extract and its constituents improved inflammatory responses by decreasing the levels of nitrite, PGE2, IL‐6, and IL‐8 via NF‐κB inhibition. The ginger extract also increased the TEER and decreased the transfer of FITC‐dextran from the apical side of the epithelium to the basolateral side. Taken together, these results show that ginger extract may be developed as a functional food for the maintenance of gastrointestinal health.     

Resveratrol Regulates Activated Hepatic Stellate Cells by Modulating NF‐κB and the PI3K/Akt Signaling Pathway

In the present study, we investigated whether resveratrol could suppress the hepatic fibrogenesis in activated hepatic stellate cells. The immortalized rat hepatic stellate cells, t‐HSC/Cl‐6, were treated with resveratrol 1 h prior to lipopolysaccharide (LPS, 1 μg/mL). Resveratrol decreased t‐HSC/Cl‐6 cell viability at much lower concentrations within 24 h. Resveratrol pretreatment also decreased the LPS‐induced protein expression of α‐SMA and collagen I. In addition, resveratrol significantly reduced the protein expression of Toll‐like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88), and the expression of phosphorylated phosphatidylinositol 3‐kinase (PI3K) and phosphorylated serine/threonine kinase B (Akt). Moreover, resveratrol markedly blocked the translocation of nuclear factor (NF)‐κB in LPS‐activated HSCs. Furthermore, resveratrol inhibited HSCs activation through stimulating LXRβ, but did not influence LXRα. Overall, we conclude that the antifibrotic effect of resveratrol is the result of blocking NF‐κB activation and PI3K/Akt phosphorylation, which inhibits HSC activation to obstruct liver fibrosis. Thus, resveratrol may be a natural agent for preventing hepatic fibrosis.     

Tomato powder impedes the development of azoxymethane‐induced colorectal cancer in rats through suppression of COX‐2 expression via NF‐κB and regulating Nrf2/HO‐1 pathway

Cancer is one of the leading causes of death worldwide. Since dietary factors have been connected to a reduced risk of a diversity of human cancers, in this study we investigated the effects of tomato powder (TP) on the development of azoxymethane (AOM)‐induced colorectal cancer in Wistar rats, and possible mechanism(s) by which TP shows its chemopreventive activity. Here we show that TP added to feed at 5% rate decreases the rate of aberrant crypt foci (ACF) and reduces the development of adenocarcinoma and growth of AOM‐induced colorectal cancer in rats. In addition, we demonstrate that TP supplementation shows its chemopreventive activities through inhibition of cyclooxygenase‐2 (COX‐2) expression via NF‐κB pathway and promotion of apoptosis, as well as regulating Nrf2/HO‐1 signaling pathway in colorectal tissue of AOM‐treated rats. Our findings identify an intimate connection between dietary supplementation of TP and the decreased risk of colorectal cancer in rats, and suggest that consumption of TP would be a natural candidate for the prevention of colorectal cancer in men.     

Sesamin attenuates intercellular cell adhesion molecule‐1 expression in vitro in TNF‐α‐treated human aortic endothelial cells and in vivo in apolipoprotein‐E‐deficient mice

Sesame lignans have antioxidative and anti‐inflammatory properties. We focused on the effects of the lignans sesamin and sesamol on the expression of endothelial‐leukocyte adhesion molecules in tumor necrosis factor‐α (TNF‐α)‐treated human aortic endothelial cells (HAECs). When HAECs were pretreated with sesamin (10 or 100 μM), the TNF‐α‐induced expression of intercellular cell adhesion molecule‐1 (ICAM‐1) was significantly reduced (35 or 70% decrease, respectively) by Western blotting. Sesamol was less effective at inhibiting ICAM‐1 expression (30% decrease at 100 μM). Sesamin and sesamol reduced the marked TNF‐α‐induced increase in human antigen R (HuR) translocation and the interaction between HuR and the 3'UTR of ICAM‐1 mRNA. Both significantly reduced the binding of monocytes to TNF‐α‐stimulated HAECs. Sesamin significantly attenuated TNF‐α‐induced ICAM‐1 expression and cell adhesion by downregulation of extracellular signal‐regulated kinase 1/2 and p38. Furthermore, in vivo, sesamin attenuated intimal thickening and ICAM‐1 expression seen in aortas of apolipoprotein‐E‐deficient mice. Taken together, these data suggest that sesamin inhibits TNF‐α‐induced extracellular signal‐regulated kinase/p38 phosphorylation, nuclear translocation of NF‐κB p65, cytoplasmic translocalization of HuR and thereby suppresses ICAM‐1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that sesamin may prevent the development of atherosclerosis and inflammatory responses.