Quercetin for brain diseases: Preclinical evidence and therapeutic potentials.

This review compiles the preclinical evidence on the therapeutic effects of quercetin in brain diseases, outlines its underlying mechanisms and highlights new insights and future research needs. Quercetin shows robust preclinical efficacy across diverse models of brain diseases, improving neurological function as well as cognitive and behavioral outcomes. The reported benefits include reductions in infarct volume, blood-brain barrier (BBB) disruption, inflammation and oxidative damage, with trends toward structural and functional recovery. These effects stem from pleiotropic, multi-target mechanisms, most consistently involving antioxidant, anti-apoptotic and anti-inflammatory actions, as well as modulation of mitochondrial function and regulation of cell-death/quality-control pathways (e.g., autophagy and ferroptosis). Studies also describe delivery strategies (e.g., nanoparticles, liposomes and exosomes) and combination regimens that enhance brain delivery and overall efficacy. However, its clinical translation is hampered by the BBB permeability and the hormetic dose-response properties of quercetin. Evidence suggests that the dose- and timing-dependent bidirectional effects imply a relatively narrow therapeutic window and potential toxicity or loss of protection at high doses or under specific conditions. Quercetin is a promising neuroprotective candidate or adjunctive strategy that can synergistically target multiple pathological processes associated with brain diseases. These findings provide valuable information for the discovery of new drugs from traditional medicines and natural products. However, translation is constrained due to its poor aqueous solubility, limited bioavailability, suboptimal BBB penetration and rapid metabolism, as well as the need to define safety limits related to dose-, schedule- and metabolite-dependent bidirectional effects. Future work should optimize the delivery system and appropriate combinations, clarify exposure-response relationships, elucidate key active metabolites and long-term safety profiles, define appropriate patient populations and confirm clinically significant benefits through rigorous clinical studies. Please cite this article as: Fang XL, Chen HR, Xu ZQ, Xu JQ, Yin XY, Yang HY, Wang Q, Huang SQ. Quercetin for brain diseases: Preclinical evidence and therapeutic potentials. J Integr Med. 2026; Epub ahead of print.