Mustard Leaf Extract Regulates Gut Microbiota and Wnt/JNK and NF-κB p65/COX-2 Signaling Pathways in a Mouse Colon Cancer Model
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Abstract:
The therapeutic effects of mustard leaf extract, glucosinolate (GSL), on colon cancer were investigated. Total GSL content in mustard leaf was quantified using UV spectrophotometry. A colon cancer model associated with colitis was developed in Balb/c mice using azoxymethane and dextran sulfate sodium. The mice were divided into control, model, and low/high-dose mustard leaf GSL groups. After a 9-week trial, inflammatory cytokine levels and NF-κB p65/COX-2 and Wnt/JNK signaling pathway activities were analyzed. The gut microbiota was examined through high-throughput sequencing of 16S rRNA. Total GSL content in mustard leaf reached 127.11 μmol/g. Compared with the model group, the high-dose mustard leaf GSL group showed significant respective increases in weight and colon length (42.11% and 20.37%, respectively (P<0.05)), a significant reduction in the number of colon tumors (P<0.05), decreases in IL-6, TNF-α, and IL-17 expression in colon tissue by 46.88%, 70.22%, and 20.43% respectively, a 98.55% increase in IFN-γ expression, and significant decreases in NF-κB p65, COX-2, Wnt, and JNK protein expression by 60.91%, 15.57%, 63.31%, and 96.58%, respectively (P<0.05). The abundances of Bacteroides, Turicibacter, Ruminococcaceae UCG-014, Ruminiclostridium_5, Akkermansia, norank f Clostridiales vadinBB60 group, Prevotellaceae UCG-001, and Blautia were significantly altered by mustard leaf GSL, resulting in a restoration of a healthy microbial balance in the gut. In summary, leaf mustard GSL is a potential adjuvant therapy for colon cancer, as evidenced by its capacity to alleviate pathological conditions and modulate inflammatory cytokines, signaling pathways, and gut microbiota in mouse models of colon cancer.
