Oolonghomobisflavan B Ameliorates Scopolamine-Induced Cognitive Impairment via BDNF-CREB Signaling and Antioxidant Mechanisms in Mice

Cognitive impairment, including memory deficits, is a major concern in neurological disorders. Natural polyphenolic compounds have emerged as promising neuroprotective agents due to their antioxidant and anti-inflammatory properties. Previously, we identified a receptor for oolonghomobisflavan B (OHBFB). OHBFB, a polyphenol derived from oolong tea, has shown strong radical-scavenging activity, but its effects on cognitive function and underlying mechanisms remain largely unknown. In this study, mice were orally administered OHBFB (10, 30, 50 mg/kg) for 15 days, followed by scopolamine-induced memory impairment. Behavioral assessments were performed using the novel object recognition (NOR) test and the closed-arm T- maze test. Molecular analyses of brain tissues included Western blotting for brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding protein (p-CREB). Safety assessments (body weight and organ weights) and antioxidant capacity (DPPH assay, IC₅₀ = 4.40 μM and ABTS assay, IC₅₀ = 4.08 μM) were also conducted. NOR: novel-object exploration rose from 49.7% (control) to 51.5%, 54.2%, and 59.9% with OHBFB 10, 30, 50 mg/kg. T-maze: performance shifted from 50.5% (control) to 49.6%, 55.1%, and 61.5% at the same doses. Expression of BDNF and p-CREB in brain tissue was restored to near-normal levels in OHBFB -treated groups. OHBFB also exhibited potent antioxidant activity, consistent with its neuroprotective effects, while showing no adverse effects on body weight or organ indices. These findings suggest that, within a scopolamine-induced amnesia mouse model, OHBFB improves cognitive performance while engaging the BDNF-CREB pathway. Given its safety profile, OHBFB may serve as a promising candidate for the treatment of cognitive impairments, including those associated with neurodegenerative disorders.