Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer (CRC) and have potential therapeutic applications for the condition. Fisetin, a natural flavonoid found in various fruits and vegetables, has shown promise in managing CRC due to its diverse biological activities. It has been found to influence key cell signaling pathways related to inflammation, angiogenesis, apoptosis, growth factors, and transcription factors. The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms. It impacts the p53 pathway, leading to increased levels of p53 and decreased levels of MDM2, contributing to apoptosis induction. Fisetin also triggers the release of important components in the apoptotic process, such as Smac/DIABLO and cytochrome c. Furthermore, fisetin inhibits the COX2 and Wnt/EGFR/NF-ĸB signaling pathways, reducing Wnt target gene expression and hindering colony formation. It achieves this by regulating the activities of CDK2 and CDK4, reducing Rb phosphorylation, decreasing cyclin E levels, and increasing p21 levels, ultimately influencing E2F-1 and CDC2 protein levels. Additionally, fisetin has various effects on CRC cells, including inhibiting the phosphorylation of YB-1 and RSK, promoting the phosphorylation of ERK1/2, and disrupting the repair process of DSBs. Moreover, fisetin serves as an adjunct therapy for the prevention and treatment of PIK3CA-mutant CRC, resulting in a reduction of PI3K expression, AKT phosphorylation, mTOR activity, and downstream target proteins in CRC cells with a PIK3CA mutation. These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.

This study conducted an investigation into the impact of different dosages of vitamin E supplementation on histopathological alterations, cognitive behaviors, and the expression of age-associated genes in the heart and hippocampus of aged mice. Mice at 12 months of age received varying doses of vitamin E (100 mg/kg, 200 mg/kg, and 400 mg/kg) orally through gavage for 28 days. The results indicated that vitamin E supplementation improved working memory and spatial learning, reduced oxidative stress in the heart and brain tissues, and positively influenced the expression of SIRT1, Nrf2, and Calstabin2 genes. Interestingly, the efficacy of vitamin E was dose-dependent, with higher doses demonstrating more beneficial effects. The study also examined the influence of vitamin E on the activities of antioxidant enzymes, such as SOD and GPX, as well as the levels of MDA, a marker of oxidative stress, and found that vitamin E supplementation resulted in dose-related changes in these parameters. The findings also indicate that higher doses of vitamin E, particularly at 400 mg/kg, demonstrated more beneficial effects. However, the study emphasizes the need for further research to confirm these findings and to explore the potential clinical applications of vitamin E supplementation in addressing age-related conditions.