Brucine Prevents DMH Induced Colon Carcinogenesis in Wistar Rats

Abdulaziz S. Saeedan, Majid Ahmad Ganaie, Basit Latief Jan, Hassan Madhkali, Mohd Nazam Ansari, Najeeb U. Rehman, Summya Rashid and Muneeb U. Rehman

Background and Objectives: Brucine is one of the abundantly found alkaloid constituent of semen strychnine, it has amazing pharmacological profile and is known to be helpful in preventing many health ailments. Our study is designed to demonstrate the beneficial role of Brucine in experimental colon carcinogenesis and exploring the possible mechanisms involved e.g., Nrf-2 cascade and downstream inflammatory pathways involved. Materials and Methods: For experimental set up animals were allocated to four groups with six animals in each group (Group I-IV). Control group (group I) was given the vehicle orally. Group II, III and IV were given 1,2, dimethylhydrazine at the dose rate of 20 mg kg^–1 b.wt. Group III and IV were treated with Brucine at a dose rate of 2 and 4 mg kg^–1 b.wt., respectively continuous for first five weeks and animals were euthanized after 16 weeks. Results: It observed an increase in the level of MDA and ROS, activity of cytochrome P450-2E1 and serum marker enzyme carcinoembryonic antigen (CEA) were also elevated, inflammatory and proliferative proteins showed increased expression. Nrf-2 and NF-κB were downregulated by DMH treatment. Brucine treatment resulted in restoration of activity of the CEA and cytochrome P450-2E1. Expression of inflammatory (Cox-2, i-NoS, IL-6, TNF-α) and proliferative markers (PCNA, Ki-67) were also suppressed by Brucine. Brucine showed great potential in preventing mucosal damage. Conclusion: Considering all results from our study Brucine could be considered as an excellent chemo-preventive in chemically induced colon malignancies. More in depth studies are required to investigate the role of Brucine in modulating other pathways involved in colon malignancies.

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