Chemopreventive Potential of Diosgenin Against 1,2-Dimethylhydrazine-Induced Colorectal Cancer in Albino Wistar Rats

Abstract

Introduction: Colorectal cancer (CRC) is a leading global health concern, ranking third in incidence and second in cancer-related mortality. Limitations of conventional therapies, such as toxicity and resistance, have driven interest in naturally occurring compounds like diosgenin, a steroidal saponin known for its antioxidant, anti-inflammatory, and anticancer properties.

Objectives: The present study aimed to evaluate the chemopreventive efficacy of diosgenin against 1,2-dimethylhydrazine (DMH)-induced colorectal cancer in Albino Wistar rats. The investigation focused on diosgenin’s ability to attenuate preneoplastic lesions, preserve colonic architecture, and mitigate oxidative stress through dose-dependent interventions.

Methods: Rats were divided into five groups: normal control, DMH-treated toxic control, standard treatment (Tamoxifen), and diosgenin-treated groups at low (20 mg/kg) and high doses (80 mg/kg). DMH (20 mg/kg/week) was administered subcutaneously for six weeks. Therapeutic assessment included body weight variation, gastric pH and acidity, oxidative stress markers (GSH, SOD, catalase, TBARS, and PC), aberrant crypt foci (ACF) analysis, scanning electron microscopy (SEM), and histopathological evaluation (H&E staining).

Results: DMH exposure resulted in significant weight loss, increased gastric acidity, elevated oxidative stress, and pronounced ACF formation. Diosgenin, especially at high doses, significantly improved antioxidant status, reduced ACF number, preserved mucosal integrity, and restored near-normal histological features.

Conclusions: Diosgenin exhibits strong chemopreventive potential against DMH-induced colorectal carcinogenesis by restoring antioxidant defences, reducing preneoplastic lesions, and maintaining histological and structural integrity. These findings support diosgenin’s role as a promising natural agent in CRC prevention and therapy.