Polymethoxylated flavones for modulating signaling pathways in inflammation

Abstract

Aberrant signaling pathways play a crucial role in the pathogenesis of various diseases, including inflammatory disorders and autoimmune conditions. Polymethoxylated flavones (PMFs), a class of natural compounds found in citrus fruits, have obtained increasing attention for their potential therapeutic effects in modulating inflammatory responses. Although significant progress has been made in the pharmacological research of PMFs, the mechanisms by which they modulate signaling pathways to treat inflammation have not been systematically reviewed or analyzed. To address this gap in the literature, this review explores the mechanisms underlying the anti-inflammatory properties of PMFs and their prospects as drugs for treating inflammatory diseases. We discuss the molecular targets and signaling pathways through which PMFs exert their anti-inflammatory effects, including NF-κB pathway, PI3K/Akt pathway, MAPK pathway, Nrf2 pathway, and regulation of inflammatory cytokine production. Furthermore, we highlight preclinical studies evaluating the efficacy of PMFs in various inflammatory conditions, such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and osteoarthritis (OA). Despite promising findings, challenges remain in optimizing the pharmacokinetic properties and therapeutic efficacy of PMFs for clinical use. Future research directions include elucidating the structure–activity relationships of PMFs, developing novel delivery strategies, and conducting large-scale clinical trials to validate their efficacy and safety profiles. Overall, PMFs represent a promising class of natural compounds with potential applications as anti-inflammatory drugs, offering novel therapeutic opportunities for managing inflammatory diseases.