Protective effects of a highly water-soluble rutin on cognitive dysfunction in mice

Dementia involves progressive cognitive decline, impairing daily and social activities. As no current drugs can reverse this decline, preventive strategies using functional compounds are gaining attention. Rutin, a flavonoid with neuroprotective and vascular benefits, has limited bioavailability due to poor water solubility. Although enzymatic glycosylation improves its solubility, it contains multiple compounds with differing numbers of sugar units and is not a single compound. To address this, EubioQuercetin®, a novel water-soluble rutin (wsRutin) formulation, was developed using L-arginine and ascorbic acid, without enzymatic processing. Here, we evaluated the neuroprotective effects of quercetin and isorhamnetin, the major metabolites of rutin, and compared the cognitive effects of rutin suspension and wsRutin solution in mice. Quercetin and isorhamnetin suppressed glutamate-, menadione- and H₂O₂-induced cell death and glutamate-induced reactive oxygen species production in HT22 mouse hippocampal cells. The oral administration of wsRutin solution significantly improved scopolamine- and MK-801-induced cognitive impairment in the novel object recognition test. wsRutin solution also enhanced the expression of brain-derived neurotrophic factor (BDNF)-related proteins in the hippocampus, including BDNF pro-peptide, p-TrkB, p-CREB, PKCα, NR1, HO-1 and NQO1. These findings suggest that wsRutin improves cognitive function via activating BDNF/TrkB signaling or antioxidant mechanism and may represent a preventive agent for dementia.