Effect of Fermented Spirulina maxima Extract on Cognitive‐Enhancing Activities in Mice with Scopolamine‐Induced Dementia

This work provides the first demonstration that Spirulina maxima extract fermented with the lactic acid bacterium Lactobacillus planetarium HY‐08 has the ability to ameliorate scopolamine‐induced memory impairment in mice. The fermented extract exhibited good cognitive‐enhancing activities, as demonstrated through Morris water maze and passive avoidance experiments: in these tests, the mice administered the fermented extract at a dose of 400 mg/kg exhibited an escape latency time and a latency time of 88.5 and 76.0 sec, respectively, whereas those administered donepezil, which was used as a positive control, showed an escape latency time and a latency time of 81.3 and 83.3 sec, respectively. However, an extract of 200 mg/kg was considered economically feasible for maintaining relatively high memory‐improving activities because only a slight difference in activities was found between 200 and 400 mg/kg. The study also provides the first demonstration that β‐carotene, one of the major bioactive substances in S. maxima, has memory‐enhancing activity. A detailed analysis of the mechanism for the cognitive‐enhancing activities of the fermented extract revealed that the fermented extract effectively increased the phosphorylation of both extracellular signal‐regulated kinases (p‐ERK) and p‐cAMP response element‐binding protein (p‐CREB) and sequentially upregulated the expression of brain‐derived neurotrophic factor (BDNF), whose signaling pathway responds to a reduction in oxidative stress in the brain. The results indicate that the improved efficacy of the fermented extract was likely due to the synergistic effects of β‐carotene and other bioactive substances. Therefore, it can be concluded that the fermented extract exerts memory‐improving effects in the hippocampus of scopolamine‐treated mice through an initial increase in ERK signaling and a sequential induction of the expression of p‐CREB and BDNF, and these effects are related to the antioxidant activities of β‐carotene and other components.