Ishige foliacea Water Extract (KDC22-01) Attenuates Tau Hyperphosphorylation and Ameliorates Scopolamine-Induced Memory Impairment in Mice

Background/Objectives: Ishige foliacea is an edible brown alga containing bioactive polyphenols with reported neuroprotective properties. Although extracts of I. foliacea have previously been shown to ameliorate cognitive impairment, their effects on pathological tau phosphorylation remain poorly characterized. This study investigated the neuroprotective and cognition-modulating effects of KDC22-01, an aqueous extract of I. foliacea. Methods: KDC22-01 was chemically characterized by total polyphenol and flavonoid-equivalent contents and HPLC fingerprinting. Its effects on pre-aggregated Aβ25–35-induced cytotoxicity and okadaic acid (OA)-induced tau phosphorylation were evaluated in SH-SY5Y cells. Cognitive performance and hippocampal tau phosphorylation were further assessed in male C57BL/6 mice with scopolamine (SCO)-induced cognitive impairment following oral KDC22-01 administration (100 or 300 mg/kg). Results: KDC22-01 protected SH-SY5Y cells against Aβ25–35-induced cytotoxicity, restoring cell viability from approximately 59% to 87% of control levels at 50 μg/mL. KDC22-01 also reduced the OA-induced p-tau (Ser199)/total tau ratio at 25 and 50 μg/mL. In SCO-treated mice, 100 mg/kg KDC22-01 significantly improved performance in the Morris water maze and passive avoidance test, whereas improvements in Y-maze spontaneous alternation did not reach statistical significance. Both KDC22-01 doses reduced hippocampal p-tau (Ser396), while changes in hippocampal Aβ levels were not statistically significant. Conclusions: These findings suggest that attenuation of tau hyperphosphorylation may contribute to the cognitive effects of KDC22-01 and support further investigation of this aqueous I. foliacea extract as a candidate functional-food ingredient for cognitive health.