Pharmacological evaluation of combinational treatment of herbal medicines with 5-fluorouracil for therapeutic enhancement in an animal model of colorectal cancer

Abstract

Colorectal cancer (CRC) is the most frequent cancer in developing and developed countries. Chemotherapy acts on a few biomarkers, but CRC develops and progresses because of multiple genetic and epigenetic dysregulation. The animal study was conducted according to Committee for the Purpose of Control and Supervision of Experiments on Animals and Animal Research: Reporting of In Vivo Experiments guidelines. CRC was induced by 1,2-dimethylhydrazine at 35 mg/kg in all Sprague-Dawley male rats for 10 weeks except for normal control. Later, treatment is given for 5 weeks with standard 5-fluorouracil (5-FU) and test drug (Polyherbal mixture) alone and in combination to check synergism effects. Important parameters related to carcinogenesis, such as change in body weight, modified Bowen’s score, colon length to weight ratio, liver and spleen index, complete blood count, estimation of uridine phosphorylase-1 enzyme, tumor necrosis factor-α, β-catenin by ELISA, and histopathology, were evaluated. Polyherbal mixture inhibited the UPP-1 enzyme, decreasing 5-FU toxicity on normal cells. Also, tumor necrosis factor-α and β-catenin levels were reduced significantly by combination compared to monotherapy alone. Combining chemotherapy with natural products may help reduce chemotherapy’s dose and the cost of the treatment due to toxicities and hospitalization. Standard drug (5-FU) combined with a polyherbal mixture at a high dose produces a synergistic effect and reduces 5-FU toxicity.