Protective Effects of Methanolic Leaf Extract of Citrullus colocynthis Combined with Kefir against 1,2-Dimethylhydrazine and High-Fat Diet-Induced Colorectal Cancer in Wistar Rats

Background

Colorectal Cancer (CRC) is a major global malignancy strongly influenced by diet and lifestyle. Natural products and probiotics are being explored for their chemopreventive potential.

Objectives

To evaluate the combined protective effects of Methanolic Leaf Extract of Citrullus colocynthis (MLECC) and kefir against CRC induced by 1,2-Dimethylhydrazine (DMH) and a High-Fat Diet (HFD) in Wistar rats.

Materials and Methods

Forty-two male Wistar rats were divided into four groups: control, disease (DMH + HFD), probiotic (DMH + HFD + kefir), and treatment (DMH + HFD + kefir + MLECC). Hematological indices, liver enzymes (AST, ALT, ALP), C-reactive protein, microbial enzyme activity, oxidative-stress biomarkers, Aberrant Crypt Foci (ACF), Ki-67 expression, and histopathology were evaluated. Data were analyzed by one-way ANOVA followed by Dunnett’s post hoc test.

Results

DMH + HFD exposure caused anemia, hepatic injury, inflammation, oxidative imbalance, and high ACF incidence. Kefir partly reversed these effects, while the MLECC + kefir combination normalized biochemical and histological parameters, reduced ACF by ≈60%, and suppressed Ki-67 expression (p<0.05 vs disease).

Conclusion

Co-administration of MLECC and kefir exerts synergistic antioxidants, anti-inflammatory, and antiproliferative actions, supporting their potential as adjuncts in colorectal cancer prevention.