Phytochemical Composition and Mechanistic Pharmacology of the Citrus Genus: Focus on Organic Constituents

The Citrus genus, which includes species such as Citrus medica, Citrus sinensis, Citrus paradisi, Citrus aurantiifolia, Citrus limon, and Citrus reticulata, is a wellrecognized source of diverse bioactive compounds with broad pharmacological significance. These species are rich in flavonoids, polymethoxylated flavones (PMFs), limonoids, carotenoids, and essential oils, each contributing to therapeutic effects such as antioxidant, anti-inflammatory, anticarcinogenic, and neuroprotective activities. This review comprehensively examines the phytochemical landscape and therapeutic potential of major Citrus species, emphasizing the organic structures, molecular mechanisms, and biological functions of their key constituents. Special focus is placed on structure-activity relationships (SAR), metabolic pathways, and cellular targets, including the PI3K/Akt/mTOR, Nrf2/Keap1, and NF-κB signaling axes. Recent advances in extraction techniques (e.g., green solvent technologies, metabolomics-guided screening) and analytical platforms for compound profiling are also discussed. Furthermore, the role of Citrus-derived compounds in modulating oxidative stress, inflammatory mediators, lipid peroxidation, and oncogenic pathways is elucidated. The article critically assesses existing literature, identifies translational gaps, and proposes future directions for the pharmacological development of Citrus phytoconstituents. This synthesis aims to bridge organic chemistry with pharmacognosy by detailing how structural nuances of Citrus bioactives underlie their multifaceted therapeutic profiles, offering significant promise for nutraceutical and pharmaceutical applications. DOI:10.2174/0113852728421176251124112057