Walnut phenolic extract inhibits nuclear factor kappaB signaling in intestinal epithelial cells, and ameliorates experimental colitis and colitis-associated colon cancer in mice.

PURPOSE: Walnuts (Juglans regia) are known to have anti-cancer and immunomodulatory effects. However, little information is available on the effects of walnut phenolic extract (WPE) on intestinal inflammation and colitis-associated colon cancer. METHODS: COLO205 cells were pretreated with WPE and then stimulated with tumor necrosis factor (TNF)-α. In the acute colitis model, wild type mice (C57BL/6) were administered 4% dextran sulfate sodium (DSS) for 5 days. In the chronic colitis model, interleukin (IL)-10-/- mice were administered with either the vehicle or WPE (20 mg/kg) by oral gavage daily for 2 weeks. In an inflammation-associated tumor model, wild type mice were administered a single intraperitoneal injection of azoxymethane followed by three cycles of 2% DSS for 5 days and 2 weeks of free water consumption. RESULTS: WPE significantly inhibited IL-8 and IL-1α expression in COLO205 cells. WPE attenuated both the TNF-α-induced IκB phosphorylation/degradation and NF-κB DNA binding activity. The administration of oral WPE significantly reduced the severity of colitis in both acute and chronic colitis models, including the IL-10-/- mice. In immunohistochemical staining, WPE attenuated NF-κB signaling in the colons of both colitis models. Finally, WPE also significantly reduced tumor development in a murine model of colitis-associated colon cancer (CAC). CONCLUSIONS: WPE ameliorates acute and chronic colitis and CAC in mice, suggesting that WPE may have potentials for the treatment of inflammatory bowel disease.

Walnut Phenolic Extract and Its Bioactive Compounds Suppress Colon Cancer Cell Growth by Regulating Colon Cancer Stemness.

Walnut has been known for its health benefits, including anti-cardiovascular disease and anti-oxidative properties. However, there is limited evidence elucidating its effects on cancer stem cells (CSCs) which represent a small subset of cancer cells that provide resistance against chemotherapy. This study aimed to evaluate the anti-CSCs potential of walnut phenolic extract (WPE) and its bioactive compounds, including (+)-catechin, chlorogenic acid, ellagic acid, and gallic acid. In the present study, CD133⁺CD44⁺ cells were isolated from HCT116 cells using fluorescence-activated cell sorting (FACS) and then treated with WPE. As a result, survival of the CD133⁺CD44⁺ HCT116 cells was inhibited and cell differentiation was induced by WPE. In addition, WPE down-regulated the CSC markers, CD133, CD44, DLK1, and Notch1, as well as the ß-catenin/p-GSK3ß signaling pathway. WPE suppressed the self-renewal capacity of CSCs. Furthermore, the WPE exhibited stronger anti-CSC effects than its individual bioactive compounds. Finally, the WPE inhibited specific CSC markers in primary colon cancer cells isolated from primary colon tumor. These results suggest that WPE can suppress colon cancer by regulating the characteristics of colon CSCs.

The Effect of Probiotics on Gut Microbiota during the Helicobacter pylori Eradication: Randomized Controlled Trial.

BACKGROUND: Helicobacter pylori causes chronic gastritis, gastroduodenal ulcers, and gastric cancer, and has been treated with two antibiotics (amoxicillin and clarithromycin) and proton-pump inhibitors (PPIs). However, antibiotic treatment alters the indigenous gut microbiota to cause side effects. Therefore, the effects of probiotic supplementation on therapy have been studied. Although several studies have covered the probiotics' effects, details about the gut microbiota changes after H. pylori eradication have not been evaluated. Therefore, we analyzed the influences of antibiotics and their combination with probiotics on the composition of the gut microbiota using high-throughput sequencing. METHODS: Subjects were divided into two groups. The antibiotics group was treated with general therapy, and the probiotics group with general therapy and probiotic supplementation. Fecal samples were collected from all subjects during treatments, and the influences on gut microbiota were analyzed by 16S rRNA gene-pyrosequencing. RESULTS: Three phyla, Firmicutes, Bacteroidetes, and Proteobacteria, were predominant in the gut microbiota of all subjects. After treatment, the relative abundances of Firmicutes were reduced, whereas those of Proteobacteria were increased in both groups. However, the changed proportions of the gut microbiota in the antibiotics group were higher than those in the probiotics group. In addition, the increase in the levels of antibiotic-resistant bacteria was higher in the antibiotics group than in the probiotics one. CONCLUSION: Probiotic supplementation can reduce the antibiotic-induced alteration and imbalance of the gut microbiota composition. This effect may restrict the growth of antibiotic-resistant bacteria in the gut and improve the H. pylori eradication success rate.