Unveiling the anticancer potential of isoorientin in digestive system cancers: mechanistic insights and nanoformulation strategies

Isoorientin, a C-glycosyl flavonoid belonging to the class of polyphenolic compounds, has recently gained attention for its superior pharmacological profile compared to other polyphenols in anticancer research. Unlike many flavonoids, such as quercetin or luteolin, isoorientin exhibits higher stability, stronger antioxidant capacity, and improved water solubility, which contribute to its enhanced bioefficacy and lower cytotoxicity toward normal cells. Present study examines the anticancer efficacy of the flavonoid isoorientin in gastrointestinal malignancies, elucidating its mechanisms of action and the advantages of nanoformulations for enhanced therapeutic administration. Isoorientin has strong anti-proliferative, pro-apoptotic, and anti-angiogenic properties in many digestive cancer models, including colorectal, gastric, and pancreatic cancers. These effects are facilitated by the control of dysregulated signalling pathways, including PI3K/Akt, NF-κB, and MAPK. Isoorientin also increases the susceptibility of cancer cells to chemotherapy and radiation, thereby enhancing total therapeutic effectiveness. Nano-formulation strategies, including liposome and micelle-based systems, have effectively addressed issues of solubility, bioavailability, and systemic toxicity, facilitating targeted administration, increased stability, and greater accumulation at tumour locations. Given its distinctive structural stability, multifaceted anticancer mechanisms, and compatibility with advanced delivery systems, isoorientin stands out as a promising adjunct or alternative therapeutic candidate for digestive cancers. Combining isoorientin with advanced drug delivery systems could improve current treatment outcomes. Further preclinical and clinical research is required to establish its therapeutic viability. • Isoorientin shows significant anticancer properties in gastrointestinal cancers. • Isoorientin regulates various pathways, including PI3K/Akt, NF-κB, and MAPK. • Nano-carriers enhance the solubility, stability and targeted delivery of Isoorientin. • Isoorientin enhances the exposure of cancer cells to chemo and radiation therapy.