Pterostilbene Exhibited the Anticancer Effect Against 1, 2‐Dimethylhydrazine (DMH)‐Induced Colorectal Cancer via Alteration of Oxidative Stress, Inflammation and Gut Microbiota

ABSTRACT Colorectal cancer (CRC) is the third leading cause of cancer‐related deaths worldwide. The current investigation aimed to assess the chemoprotective effects of pterostilbene against 1,2‐dimethylhydrazine (DMH)‐induced colorectal cancer in mice. An in‐silico study was conducted to perform docking studies against nuclear factor kappa factor (NF‐κB). CRC was induced in mice by administering DMH (20 mg/kg) subcutaneously, and the mice were subsequently administered various dosages of pterostilbene (5, 10, and 15 mg/kg). At the end of the study, various biochemical parameters, including inflammatory cytokines, inflammatory markers, and antioxidant enzymes, were examined. Additionally, the mice's stools were collected for the analysis of intestinal microbiota. A total of 5 hydrogen bonds were identified between NF‐κB and pterostilbene using LigPlot+. Pterostilbene significantly ( p < 0.001) reduced tumor incidence, tumor weight, and increased body weight. Pterostilbene significantly ( p < 0.001) altered the levels of lipid peroxidation, reduced glutathione, superoxide dismutase, glutathione peroxidase, and catalase as well as the activity of both phase I and phase II enzymes. Furthermore, pterostilbene significantly ( p < 0.001) decreased the levels of proinflammatory cytokines such as tumor necrosis factor‐α, interleukin‐6, interferon‐γ, and interleukin‐1β, while increasing the levels of anti‐inflammatory cytokines like interleukin‐4 and interleukin‐10. Pterostilbene considerably suppressed the levels of cyclooxygenase‐2 and prostaglandin E2, as well as inducible nitric oxide synthase and simultaneously elevated the levels of apoptosis‐related parameters, including caspase‐3, caspase‐8, and caspase‐9. Moreover, pterostilbene significantly reduced the abundance of Staphylococcus in the intestinal microbiota and enhanced the levels of beneficial bacteria, such as Bifidobacterium, Akkermansia, and Lactobacillus . Pterostilbene demonstrated a chemoprotective effect against CRC by effectively reducing oxidative stress, mitigating inflammatory responses, and inducing alterations in gut microbiota levels.