Inhibitory Effect of Garcinol on Obesity‐Exacerbated, Colitis‐Mediated Colon Carcinogenesis

Scope Epidemiological studies show a consistent and compelling association between the risk of colorectal cancer development and obesity, but its mechanisms remain poorly understood. Evidence is mounting that colorectal cancer can be prevented by nutritional supplements, such as phytochemicals. Garcinol, a polyisoprenylated benzophenone derivative, is widely present in Garcinia plants. This study investigates the potential role of garcinol supplementation in ameliorating obesity‐induced colon cancer development. Methods and Results An animal model to investigate the effect of high‐fat‐diet (HFD)‐induced obesity on promoting colitis‐associated colon cancer (AOM (azoxymethane)/DSS (dextran sodium sulfate)‐induced) is designed. The results show that HFD can promote colitis‐associated colon cancer as compared to an AOM/DSS group without the intervention of obesity, and supplementing with 0.05% garcinol in the diet can significantly ameliorate obesity‐promoted colon carcinogenesis. The results also reveals that the microbiota composition of each group is significantly different and clustered. The most representative genera are Alistipes, Romboutsia, and Ruminococcus. The RNA‐sequencing results show that the administration of garcinol can regulate genes and improve obesity‐promoting colitis‐associated colon carcinogenesis. Conclusion The study results suggest that garcinol can prevent obesity‐promoted colorectal cancer, and these findings provide important niches for the future development of garcinol as functional foods or adjuvant therapeutic agents. This study first reveals that garcinol possess the potential to prevent obesity promoted‐colorectal cancer. The chemoprevention attributes to attenuate the progression of carcinogenesis by improved various pathological values and inflammation indicators, and also alleviates the gut dysbiosis. These findings provide important niches for future development of garcinol as functional foods or adjuvant therapeutic agents.