Chemoprotective effect of pinoresinol diglucoside against 1,2-dimethylhydrazine-induced colorectal cancer through regulation of nuclear factor-kappa B/inducible nitric oxide synthase/cyclooxygenase-2 signaling and gut dysbiosis

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor that develops in the colon or rectum, usually originating from abnormal growth of cells in the intestinal lining. Pinoresinol diglucoside (PDG) is a lignan compound, which exhibits various pharmacological activities, such as anti-inflammatory, antioxidant, antihypertensive, and anticancer. The aim of the current study was to explore the anticancer effect of PDG against 1,2-dimethylhydrazine (DMH)-induced CRC. MATERIALS AND METHODS: Subcutaneous administration of DMH (20 mg/kg) was used for the induction of CRC in the rats, and the rats were received the oral administration of PDG (2.5, 5, and 10 mg/kg) for 15 weeks. The body weight, colon weight, colon length, cancer marker, phase I, II, antioxidant, cytokines, and inflammatory parameters were estimated. The messenger ribonucleic acid expression and histopathology study were also performed. The gut microbiota was estimated in the facal of all group rats. RESULTS: PDG treatment significantly (P < 0.001) improved the body weight, colon length, and colon weight, along with a reduction in the level of cancer markers such as tissue polypeptide-specific antigen, tumor-associated glycoprotein 72, carcinoembryonic antigen, and carbohydrate antigen 19.9. PDG treatment also altered the level of alkaline phosphatase, lactate dehydrogenase, phase I and II enzymes, antioxidant parameters, cytokines, and inflammatory parameters, respectively. PDG treatment significantly (P < 0.001) altered the F/B ratio and relative abundance of Bacteroidetes, Firmicutes, Actinobacteriota, and Desulfobacterota and altered the histopathological alteration. CONCLUSION: PDG exhibited a chemoprotective effect against DMH-induced CRC via regulation of the nuclear factor-kappa B/inducible nitric oxide synthase/cyclooxygenase-2 signaling and gut dysbiosis.