Citrus polymethoxyflavones as regulators of metabolic homoeostasis: Recent advances for possible mechanisms

Given the increasing obesity prevalence among adults, the metabolic syndrome (MetS) is becoming a common health concern in our modern life. The identification and exploration of dietary compounds against MetS is an attractive strategy for functional food development. Polymethoxyflavones (PMFs), abundantly existing in the citrus peels, possess a broad spectrum of bioactivities, including neuroprotection, anti-inflammation, anti-obesity, anti-arteriolosclerosis, and others. Recent studies have highlighted the critical role of circadian clock and gut microbiota on metabolic homeostasis maintained by PMFs. This review summarizes recent discoveries for PMFs' role on MetS. The metabolic homeostasis in vivo is regulated by the crosstalk of central nervous system and multiple peripheral organs. The signal pathways of PMFs against MetS in specific organs/cell models are discussed. The anti-inflammation of PMFs is considered as the fundamental for their bioactivities against MetS. PMFs show beneficial effect to modulate MetS, including improving clock dysfunction, dyslipidemia, insulin resistance, obesity and cardiovascular disease. Even though multiple signaling pathways have been explored, the interorgan communication axis needs further investigation. This review would strengthen the mechanistic understanding of PMFs' health benefits and provide scientific support for functional food development.