Pharmacological landscape of linarin: From benchside mechanisms to potential bedside applications

Linarin, a glycosylated flavonoid derived from medicinal plants such as Buddleja and Chrysanthemum species, has emerged as a bioactive compound with significant pharmacological potential. This review provides a comprehensive overview of linarin's chemical structure, extraction methods, pharmacokinetics, and therapeutic applications. Linarin exhibits diverse biological activities, including anti-inflammatory, antioxidant, neuroprotective, and anticancer effects, making it a promising candidate for drug development. The flavonoid demonstrates protective effects against hyperuricemia, acute kidney injury, spinal cord injury, ischemic stroke, diabetes, osteoporosis, and inflammatory bowel disease, primarily through modulation of signaling pathways such as Nrf2/Keap1, NF-κB, and MAPK. Additionally, linarin has shown potential in managing neurodegenerative disorders, including Alzheimer's disease, through its acetylcholinesterase inhibitory activity. Its anti-cancer effects have been linked to the inhibition of proliferation, apoptosis induction, and suppression of metastasis-related pathways in lung, prostate, and brain cancers. Moreover, recent studies highlight its potential for ameliorating osteoarthritis, liver injury, and infectious diseases. The mechanisms underlying linarin's therapeutic effects involve its ability to modulate oxidative stress, inflammation, apoptosis, and metabolic pathways. Given its low toxicity, bioavailability, and structural versatility, linarin represents a compelling natural compound for future pharmaceutical applications. However, further preclinical and clinical investigations are warranted to fully elucidate its pharmacokinetics, optimize its bioavailability, and establish its clinical efficacy. This review advances a systems-level perspective that unifies linarin's pleiotropic mechanisms across several diseases. By linking structure-activity relationships with translational bottlenecks such as poor bioavailability and limited clinical validation, we outline a forward-looking roadmap for its development as a multi-target therapeutic scaffold.