The Ameliorating Effects of Bee Pollen on Scopolamine-Induced Cognitive Impairment in Mice.

Bee pollen consists of floral pollen mixed with bee secretions and nectar. It has been considered as a functional food and has different kinds of biologically active ingredients, such as flavonoids, polyphenols, phytosterols and minerals. However, its function in cognition has yet been investigated. In the present study, we investigated the ameliorating effect of bee pollen against scopolamine-caused cognitive impairment through the passive avoidance test, the Y-maze test and the Morris water maze test. In addition, Western blotting was employed to verify the effects of bee pollen on memory-related signaling molecules in the hippocampus. Bee pollen extract (100 or 300 mg/kg, per os (p.o.)) obviously reversed scopolamine-caused cognitive impairment in the passive avoidance test, ameliorated spontaneous alternation versus the scopolamine-treated group in the Y-maze test and prolonged swimming time in the target zone in the Morris water maze test. In addition, the phosphorylation levels of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), protein kinase B (Akt) and glycogen synthase kinase-3ß (GSK-3ß), and the expression levels of brain-derived neurotrophic factor (BDNF) and tissue plasminogen activator (tPA) in the hippocampi, were increased in response to the treatment with bee pollen extract (100 or 300 mg/kg, p.o.). These results indicated that bee pollen ameliorates cognitive impairment induced by cholinergic blockade through the enhancing conversion of proBDNF to mature BDNF by tPA, probably, through the ERK-CREB pathway or Akt-GSK-3ß signaling pathway and would be a useful agent for the treatment of cognitive dysfunction.

Ethanolic Extract of Opuntia ficus-indica var. saboten Ameliorates Cognitive Dysfunction Induced by Cholinergic Blockade in Mice.

The stem of Opuntia ficus-indica var. saboten is edible and has been used as a medicinal herb on Jeju Island in Korea. We previously reported that the butanolic extract of O. ficus-indica var. saboten exerts the enhancement of long-term memory in mice. However, the antiamnesic effects of O. ficus-indica var. saboten and its mode of action has not been clearly elucidated. In the present study, we explored the effects of the ethanolic extract of stems of O. ficus-indica var. saboten (EOFS) on cognitive performance in mouse and attempted to delineate its mechanism of action. We used the passive avoidance, Y-maze, and novel object recognition tests to assess its effects on cognitive functions in scopolamine-induced memory-impaired mice. We observed that EOFS (100, 200, and 400 mg/kg) ameliorated scopolamine-induced cognitive dysfunction. We also explored its mechanism of action by conducting an acetylcholinesterase (AChE) activity assay using the mouse whole brain and Western blot using the mouse hippocampal tissue. Western blot analysis and the ex vivo study revealed that EOFS increased the levels of phosphorylated extracellular signal-regulated kinase and cAMP response element-binding protein (CREB) and the levels of brain-derived neurotrophic factor (BDNF) expression in the hippocampus. It also inhibited AChE activity in the brain. Our findings suggest that EOFS would be useful for the treatment of cholinergic blockade-induced cognitive dysfunction.

The memory ameliorating effects of DHP1402, an herbal mixture, on cholinergic blockade-induced cognitive dysfunction in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F Chow (Rhamnaceae) and the roots of Codonopsis lanceolata (Siedbold & Zucc.) Benth. & Hook. f ex Trautv. (Campanulaceae), contained in the DHP1402, have long been used for treating dementia or hypomnesia as folk medicine. AIM OF THE STUDY: It has been reported that Z. jujuba var. spinosa and C. lanceolata are effective in improving cognitive function, but via different mechanisms. Therefore, in the present study, we evaluated the synergistic effects of Z. jujuba var. spinosa and C. lanceolata on scopolamine-induced memory impairment. MATERIALS AND METHODS: Scopolamine, a cholinergic muscarinic receptor antagonist, was used to induce cognitive dysfunction. We employed several behavioral tasks to estimate the synergistic effect of the seeds of Z. jujuba var. spinosa and the roots of C. lanceolata. In addition, we introduced the Western blotting, the antagonism passive avoidance task to investigate a synergistic effect of an herbal formulation. RESULTS: Synergistic effects of a combination of Z. jujuba var. spinosa and C. lanceolata at a 5:1 ratio [(w/w), DHP1402] were observed against cognitive dysfunction in the passive avoidance and Y-maze tasks. DHP1402 also ameliorated memory deficits in a dose-dependent manner in these behavioral tasks, as well as in the Morris water maze task. According to the Western blot results, the phosphorylation levels of protein kinase A (PKA), extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) in the hippocampus were also increased in a synergistic manner after the administration of DHP1402. In addition, we found that the effects of DHP1402 on cognitive function were mediated by N-methyl-D-aspartate (NMDA) receptor signalling, based on the antagonism studies. Furthermore, we found that DHP1402 has inhibitory activity against acetylcholinesterase (AChE). CONCLUSION: DHP1402 attenuates cholinergic blockade-induced cognitive dysfunction through NMDA receptor modulation, PKA-ERK-CREB pathway activation, and AChE inhibition. Therefore, DHP1402 could be a candidate for alleviating cognitive dysfunction.

Maslinic acid ameliorates NMDA receptor blockade-induced schizophrenia-like behaviors in mice.

Schizophrenia is a chronic psychotic disorder characterized by positive, negative, and cognitive symptoms. Primary treatments for schizophrenia relieve the positive symptoms but are less effective against the negative and cognitive symptoms. In the present study, we investigated whether maslinic acid, isolated from Syzygium aromaticum (clove), can ameliorate schizophrenia-like behaviors in mice induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. After maslinic acid treatment in the MK-801 model, we examined the behavioral alteration and signaling pathways in the prefrontal cortex. Mice were treated with maslinic acid (30 mg/kg), and their behaviors were evaluated through an array of behavioral tests. The effects of maslinic acid were also examined in the signaling pathways in the prefrontal cortex. A single administration of maslinic acid blocked the MK-801-induced hyperlocomotion and reversed the MK-801-induced sensorimotor gating deficit in the acoustic startle response test. In the social novelty preference test, maslinic acid ameliorated the social behavior deficits induced by MK-801. The MK-801-induced attention and recognition memory impairments were also alleviated by a single administration of maslinic acid. Furthermore, maslinic acid normalized the phosphorylation levels of Akt-GSK-3ß and ERK-CREB in the prefrontal cortex. Overall, maslinic acid ameliorated the schizophrenia-like symptoms induced by MK-801, and these effects may be partly mediated through Akt-GSK-3ß and ERK-CREB activation. These findings suggest that maslinic acid could be a candidate for the treatment of several symptoms of schizophrenia, including positive symptoms, sensorimotor gating disruption, social interaction deficits, and cognitive impairments.

Cognitive Ameliorating Effect of Acanthopanax koreanum Against Scopolamine-Induced Memory Impairment in Mice.

Acanthopanax koreanum Nakai (Araliaceae) is one of the most widely cultivated medicinal plants in Jeju Island, Korea, and the roots and stem bark of A. koreanum have been traditionally used as a tonic agent for general weakness. However, the use of A. koreanum for general weakness observed in the elderly, including those with declined cognitive function, has not been intensively investigated. This study was performed to investigate the effect of the ethanol extract of A. koreanum (EEAK) on cholinergic blockade-induced memory impairment in mice. To evaluate the ameliorating effects of EEAK against scopolamine-induced memory impairment, mice were orally administered EEAK (25, 50, 100, or 200 mg/kg), and several behavioral tasks, including a passive avoidance task, the Y-maze, and a novel object recognition task, were employed. Besides, western blot analysis was conducted to examine whether EEAK affected memory-associated signaling molecules, such as protein kinase B (Akt), Ca2+ /calmodulin-dependent protein kinase II (CaMKII), and cAMP response element-binding protein (CREB). The administration of EEAK (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in the passive avoidance task, the Y-maze, and the novel object recognition task. The phosphorylation levels of both Akt and CaMKII were significantly increased by approximately two-fold compared with the control group because of the administration of EEAK (100 or 200 mg/kg) (p < 0.05). Moreover, the phosphorylation level of CREB was also significantly increased compared with the control group by the administration of EEAK (200 mg/kg) (p < 0.05). The present study suggests that EEAK ameliorates the cognitive dysfunction induced by the cholinergic blockade, in part, via several memory-associated signaling molecules and may hold therapeutic potential against cognitive dysfunction, such as that presented in neurodegenerative diseases, for example, Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd.