Assessment of the immunomodulatory potential of betalain- and phenolic-rich extracts from Opuntia cactus fruits

Research into natural sources of molecules that can modulate the immune system has gained significant interest in recent years, with a special emphasis on plant-based alternatives that could lead to the development of immunoceuticals. This study focused on the evaluation of the immunomodulatory potential of extracts obtained from three Opuntia varieties abundant in betalains and phenolic compounds: Opuntia stricta (var. dillenii ) whole fruit extract (OD), Opuntia ficus-indica var. Blanca peel extract (BB) and Opuntia ficus-indica var. Colorada pulp extract (COL). All three extracts from these Opuntia varieties demonstrated significant antioxidant activity in Caco-2 and HepG2 cells and stimulated phagocytosis in RAW 264.7 macrophages. Among them, OD extract exhibited the most diverse composition in betalains and phenolic compounds, and the highest immunomodulatory potential by highly inhibiting nitric oxide (NO) production and enhancing the phagocytic activity in RAW 264.7 macrophages. Consequently, its composition was fractionated by Fast Centrifugal Partition Chromatography (FCPC) to conduct a bioguided study of the compound or groups of compounds responsible for the evaluated biological activities. A total of 12 fractions were obtained (F1-F12). Overall, fractions F3, F6, and, F7 showed greater activity in modulating cytokine production and inhibition, particularly tumoral necrosis factor (TNF)-α, and interleukins (IL-6, IL-10, and IL-1β), while the whole OD extract was more effective at reducing NO production and stimulating phagocytosis. These results underscore the potential of Opuntia cactus fruits as promising candidates for the development of natural immunomodulatory agents, widening the way for future research into their application as effective immunoceuticals. • OD, BB, and COL extracts showed significant cellular antioxidant activity. • OD extract presented the highest NO inhibition and phagocytosis stimulation. • F3, F7, and F7 exhibited modulatory effects of TNF-α, IL-6, and, IL-1β production. • All OD FCPC fractions and OD extract stimulated IL-10 production. • Potential immunomodulatory compounds were identified in OD extract using FCPC.