Studies on the ameliorative potential of Rheum webbianum rhizome extracts on 1,2-dimethylhydrazine (DMH) induced colorectal cancer and associated hepatic and haematological abnormalities in swiss albino rats

Abstract

Ethnopharmacological relevanceRheum webbianum Royle (RW) holds significant ethnopharmacological importance owing to its 5000-year history of cultivation for medicinal and culinary purposes. Demonstrating therapeutic advantages in traditional and contemporary medical practices, RW exhibits key pharmacological effects including anticancer activity, gastrointestinal control, anti-inflammatory properties, and suppression of fibrosis. Despite its recognized vast bioactivities in ethnopharmacology, its efficacy against the colorectal cancer (CRC) remains incompletely understood. Aim of the studyThis study for the first time aims to investigate the chemo-preventive capabilities of various extracts derived from RW rhizomes against CRC development. Materials and methodsFour types of RW extracts were prepared by using different solvents viz: Hexane, Ethy-acetate, Ethanol and Methanol. All the four extracts were evaluated for cytotoxicity on HCT-116 human CRC cells. Promising extracts were further investigated in-vivo at varying doses using 1,2-dimethylhydrazine (DMH) induced rat CRC model to assess the anti-oxidant and anticancer properties as well as their effects on the associated hepatic deterioration and hematological alterations. ResultsCell viability: In-vitro assessments demonstrated a dose and time-dependent reduction in HCT-116 cell viability following treatment with methanolic and ethanolic extracts of RW, reducing viability by up to 85% and 90%, respectively, at 200 μg/ml. Histopathology: Histopathological analyses revealed significant improvements in colon tissue morphology in RW extract-treated groups compared to DMH-only treated animals. RW-treated groups showed reduced structural abnormalities, congestion, inflammatory cell infiltration, crypt abscess formation, and dysplasia. In contrast, the DMH-only group exhibited irregular glandular structure, mucosal destruction, extensive inflammatory cell infiltration, crypt abscess formation, and dysplasia. These results highlight the potential of RW methanolic and ethanolic extracts in mitigating colon cancer-related histopathological alterations. Haematological, and hepatic parameters: In the DMH-induced colorectal cancer rat model, significant hematological imbalances were evident, including a 49.13% decrease in erythrocytes, 32.18% in hemoglobin, and 26.79% in hematocrit, along with a 79.62% increase in white blood cells and 68.96% rise in platelets. Administration of RW rhizome extracts effectively restored these hematological parameters to levels comparable to those in the control group. Furthermore, RW treatment significantly reduced serum ALT and AST levels, which had increased by 36.78% and 33.12%, respectively, due to DMH exposure. RW intervention also mitigated the onset of atherosclerosis, evidenced by notable reductions in serum total cholesterol and triglyceride levels. Comparative analysis indicated that RW-treated DMH groups effectively restored lipid profiles, contrasting with the DMH-only group which exhibited markers indicative of colon cancer. Oxidative stress: The DMH-treated group showed a significant increase in MDA levels by 195.59%, indicative of heightened free radical production, coupled with decreased levels of SOD (33%), CAT (48%), GSH (58%), and GR activity (49%), signifying oxidative stress. Treatment with RW extracts in DMH-treated rats markedly reduced MDA levels and enhanced SOD, CAT, GSH, and GR activities. These results underscore the antioxidant efficacy of RW extracts. ConclusionThis study underscores the significant potential of RW rhizome extracts in inhibiting colorectal cancer development. Further investigations are warranted to identify the active constituents responsible for these promising outcomes, positioning RW as a natural and potential agent in combating colon cancer.