4. Discussion
obesity, colorectal cancer, TNF-α, colorectal adenomas, inflammation, dysplasia, adenomatous polyp, carcinoma, colon carcinogenesis, Inflammation, satiety, adenoma
OBESITY, COLORECTAL CANCER, ADENOMATOUS POLYPS, INFLAMMATION, ABNORMAL CELL PROLIFERATION, ADENOMATOUS POLYP, CARCINOMA, DYSPLASIA, DYSPLASTIC, INFLAMMATION, ADENOMA, CHRONIC INFLAMMATION
The findings from our study provide valuable insights into the complex relationships between biomarkers and treatment outcomes of curcumin and anthocyanin in patients with adenomatous polyps. Notably, no significant differences in biomarker levels or their changes were observed across the treatment arms, indicating that the interventions may not have directly influenced these specific biomarkers. However, our network analysis revealed compelling patterns, including direct correlations between adiponectin and BMI and glycemia, as well as direct links between inflammatory biomarkers and between leptin and BMI. These correlations potentially reflect disruptions in metabolic regulation that could contribute to adenomatous polyp development or progression. The direct link between leptin and BMI might indicate a complex interaction between the excess of body weight and signaling related to adenomatous polyp growth. These connections shed light on the complex interplay between metabolic and inflammatory pathways that could contribute to adenomatous polyp development or progression. These findings offer avenues for further research into preventive or therapeutic strategies targeting metabolic and inflammatory pathways contributing to the adenoma–carcinoma sequence in CRC development.Moreover, we detected an inverse relationship between post-treatment adiponectin levels and Ki67 levels in dysplasia tissue, suggesting a potential role of this adipokine in dysplasia progression. Adiponectin is a hormone secreted by adipose tissue that plays a role in regulating glucose and lipid metabolism. It is also involved in various anti-inflammatory and anti-tumorigenic processes [The finding of an inverse correlation between adiponectin and Ki67 levels in dysplasia tissue suggests a potential relationship between adiponectin levels and the severity of dysplasia. One possible explanation for this correlation is the role of adiponectin in inflammation. Adiponectin has been shown to have anti-inflammatory effects by suppressing the production of pro-inflammatory molecules and promoting the release of anti-inflammatory factors. Inflammation plays a crucial role in the development and progression of dysplasia, and lower levels of adiponectin could contribute to a pro-inflammatory environment that facilitates dysplasia [Equally noteworthy was the observed increase in IL-6 at the end of treatment in subjects with high baseline dysplasia grade, suggesting a composite interplay between dysplasia severity and inflammatory processes. The expected outcome of treatment with the natural compounds curcumin and anthocyanins would be a reduction in dysplasia grade and a decrease in inflammation, given their anti-inflammatory properties. However, the observed increase in IL-6 could be counterintuitive, since IL-6 is associated with inflammation, and increased levels might suggest a pro-inflammatory response. The mechanism by which IL-6 could be involved in dysplasia progression is not fully understood. One possible explanation is that chronic inflammation sustained by granulocytes, plasma cells, lymphocytes, and macrophages results in high levels of pro-inflammatory cytokines. IL-6 in particular creates a microenvironment conducive to abnormal cell proliferation and promotes the survival of dysplastic cells, inhibiting apoptosis and possibly contributing to their progression toward cancerous changes [The observation of a greater IL-10 increase in subjects with BMI < 25 compared to BMI > 25 is an interesting finding that suggests a potential relationship between body weight and the immune response. IL-10 is an anti-inflammatory cytokine that plays a crucial role in dampening the immune response and reducing inflammation [Surprisingly, our study did not yield evidence of curcumin inhibiting TNF-α, which could be primarily attributed to the limitations of a small sample size. Notably, recent research through a systematic review and meta-analysis of randomized controlled trials, indicated that with increasing doses of curcumin, there was a trend towards a greater reduction in TNF-α levels [The finding that subjects with low anthocyanin food intake show a greater reduction in leptin levels suggests a potential relationship between anthocyanin dietary consumption and leptin regulation. Leptin is a hormone produced by adipose tissue that plays a central role in appetite regulation and energy balance. Higher leptin levels generally signal satiety and a reduced appetite, while lower levels may lead to increased hunger and food intake [It is interesting to note that subjects with a positive family history of colorectal cancer had greater circulating levels of IGFBP-3 at the end of the trial than subjects without a family history. IGFBP-3 is a multifunctional protein that regulates the activity of insulin-like growth factors (IGFs) and plays a crucial role in cell growth, differentiation, and apoptosis [The finding of a trend to lower adiponectin levels in subjects with colorectal adenomas taking curcumin and anthocyanins compared to placebo is an unexpected result. A comprehensive systematic review and meta-analysis of 60 randomized controlled trials found that curcumin/turmeric supplementation improved anthropometric indices of obesity and increased adiponectin levels in the general population [The study has several limitations, including the small sample size and the short duration of intervention, which may have precluded the achievement of a significant modulation of circulating biomarkers of colon carcinogenesis related to inflammation and metabolism.