Phenolic Extracts of Hulless Barley Grass Alleviate Progression of Colitis‐Related Colorectal Cancer by Inhibiting the Overexpression of Wnt/β‐Catenin Signaling Pathway

Ulcerative colitis (UC), a precursor of colorectal cancer (CRC) driven by Wnt/β-Catenin pathway activation, may be mitigated by hulless barley grass (HBG), a high-altitude crop with antioxidant, anti-inflammatory, and anti-tumor effects. A previous study found that HBG had palliative effects on UC. The effects and mechanism of HBG phenolic (PE), polysaccharide (PSE), and lipid extracts (LE) on UC associated CRC were investigated by establishing an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC mice model. Compared to CRC mice, the PE group (600 mg/kg/d) exhibited a 41.4% decrease in tumor numbers and a 16.5% decrease in the proportion of tumors more than 2 mm in size. In addition, PE effectively alleviated the expression of pro-inflammatory cytokines, including tumor necrosis factor-α (Tnfα), interleukin-6 (Il6), and Il1β, and genes associated with tumorigenesis (prostaglandin-endoperoxide synthase 2 (Ptgs2), epidermal growth factor receptor (Egfr), and nitric oxide synthase 2 (Nos2), and increased the diversity and abundance of intestinal flora. Quercetin-3-O-(2″,6″-α-L-dirhamnopyranosyl)-β-D-galactopyranoside, Quercetin-3-O-β-D-rutinoside, and Baicalin-7-diglucoside were identified as the main components of PE. Furthermore, PE downregulated β-Catenin (Ctnnb1) from 4.81 to 1.46 fold change, Myc from 4.27 to 1.62 (fold), and Cyclin D1 (Ccnd1) from 5.43 to 2.35 fold. Both PSE (400 mg/kg/d) and LE (200 mg/kg/d) significantly decreased Tnfα and Il6 mRNA expression, and no significant difference in Ptgs2 and Egfr was observed between the PSE and LE groups and the model group. These findings indicated that PE had the potential to treat CRC, providing a preventive strategy for UC associated CRC. PRACTICAL APPLICATIONS: This research indicates that phenolic extracts from hulless barley grass have potential for development as natural dietary supplements or functional food ingredients aimed at preventing colitis-associated colorectal cancer. By significantly reducing pro-inflammatory cytokines and suppressing aberrant initiation of the Wnt/β-catenin signaling pathway, these extracts may alleviate chronic intestinal inflammation. In addition, they contribute to the maintenance of a healthier gut microbiota, thereby supporting intestinal barrier function. Together, these findings highlight a promising natural strategy to improve gut health and lower the risk of inflammation-related colorectal cancer.