Citrus fruits contain flavonoids that exhibit various physiological activities. They have been utilized as fruits, foods, and supplements that may exert favorable effects on health. Among these flavonoids, the physiological functions of polymethoxylated flavonoids (PMFs) have been investigated. Nobiletin (3’,4’,5,6,7,8-hexamethoxyflavone), a naturally occurring functional ingredient, is a representative PMF compound that is abundant in the peels of citrus fruits, such as Shikuwasa (Citrus depressa). A method to manufacture material (Nobiletin high-purity powder: PMF90) with high-purity nobiletin and tangeretin from the citrus peel of C. depressa was developed, and includes dehydrating the peel, extracting the dried peel with ethanol, and treating extracts with alkaline. The physiological activities of nobiletin were extensively examined mainly by preclinical research, including cultured cell, tissue, and diseased animal models, and it was shown to have various functions, such as anti-inflammation, anti-obesity, and anti-diabetes, cognitive improvement, and biological clock regulation. Preclinical and clinical studies demonstrated that nobiletin and Shikuwasa peel extract (PMF90), which contains high-purity nobiletin, attenuated memory/learning impairments and urinary dysfunction.
Yamada et al. (2025) studied this question.