Theracurmin Ameliorates Cognitive Dysfunctions in 5XFAD Mice by Improving Synaptic Function and Mitigating Oxidative Stress.

As the elderly population is increasing, Alzheimer's disease (AD) has become a global issue and many clinical trials have been conducted to evaluate treatments for AD. As these clinical trials have been conducted and have failed, the development of new theraphies for AD with fewer adverse effects remains a challenge. In this study, we examined the effects of Theracurmin on cognitive decline using 5XFAD mice, an AD mouse model. Theracurmin is more bioavailable form of curcumin, generated with submicron colloidal dispersion. Mice were treated with Theracurmin (100, 300 and 1,000 mg/kg) for 12 weeks and were subjected to the novel object recognition test and the Barnes maze test. Theracurmin-treated mice showed significant amelioration in recognition and spatial memories compared those of the vehicle-treated controls. In addition, the antioxidant activities of Theracurmin were investigated by measuring the superoxide dismutase (SOD) activity, malondialdehyde (MDA) and glutathione (GSH) levels. The increased MDA level and decreased SOD and GSH levels in the vehicle-treated 5XFAD mice were significantly reversed by the administration of Theracurmin. Moreover, we observed that Theracurmin administration elevated the expression levels of synaptic components, including synaptophysin and post synaptic density protein 95, and decreased the expression levels of ionized calcium-binding adapter molecule 1 (Iba-1), a marker of activated microglia. These results suggest that Theracurmin ameliorates cognitive function by increasing the expression of synaptic components and by preventing neuronal cell damage from oxidative stress or from the activation of microglia. Thus, Theracurmin would be useful for treating the cognitive dysfunctions observed in AD.

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.

The ethanolic extract of the Eclipta prostrata L. ameliorates the cognitive impairment in mice induced by scopolamine.

ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrata L. (Asteraceae) has been prescribed for whole body nourishment and nervine tonic in Asia. However, the effects of E. prostrata in learning and memory have not been fully explored. AIM OF THE STUDY: To scientifically elucidate the effects of E. prostrata on cognitive functions, we examined whether E. prostrata could ameliorate a cholinergic blockade-induced memory impairment, and we also investigated the effects of E. prostrata on the synaptic plasticity in the hippocampus. MATERIALS AND METHODS: Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist. The anti-amnesic effects of the ethanolic extract of Eclipta prostrata L. (EEEP) were measured in mice by the passive avoidance, Y-maze and Morris water maze tasks. To test the effects of EEEP on synaptic plasticity, we measured long-term potentiation (LTP) in the hippocampus. We also studied several signaling molecules related to learning and memory, such as phosphorylated protein kinase B (Akt) or phosphorylated glycogen synthase kinase-3ß (GSK-3ß). RESULTS: In the passive avoidance task, EEEP (50 or 100mg/kg, p.o.) significantly ameliorated the shortened step-through latency induced by scopolamine. EEEP (100mg/kg, p.o.) also showed significant increase in alternation behavior during the Y-maze task. In the Morris water maze task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by EEEP (50 or 100mg/kg, p.o.). Moreover, EEEP (100µg/ml) significantly enhanced hippocampal LTP without affecting basal synaptic transmission. The administration of EEEP (100mg/kg) increased the phosphorylation levels of Akt and GSK-3ß in the hippocampal region. CONCLUSION: These results suggest that EEEP has memory-ameliorating activity against scopolamine-induced cognitive impairment and facilitates LTP in the hippocampus. This could be, at least in part, mediated by the activation of the Akt-GSK-3ß signaling pathway.

Positive effects of ß-amyrin on pentobarbital-induced sleep in mice via GABAergic neurotransmitter system.

Sleep loss, insomnia, is considered a sign of imbalance of physiological rhythm, which can be used as pre-clinic diagnosis of various neuropsychiatric disorders. The aim of the present study is to understand the pharmacological actions of α- or ß-amyrin, natural triterpene compound, on the sleep in mice. To analyze the sleeping behavior, we used the well-known pentobarbital-induced sleeping model after single administration of either α- or ß-amyrin. The sleeping onset time was remarkably decreased and duration was prolonged by ß-amyrin (1, 3, or 10mg/kg) but not by α-amyrin (1, 3, or 10mg/kg). These effects were significantly blocked by GABAA receptor antagonist, bicuculline. Moreover, ß-amyrin increased brain GABA level compared to the vehicle administration. Overall, the present study suggests that ß-amyrin would enhance the total sleeping behavior in pentobarbital-induced sleeping model via the activation of GABAergic neurotransmitter system through GABA content in the brain.

Ursolic acid enhances pentobarbital-induced sleeping behaviors via GABAergic neurotransmission in mice.

Prunella vulgaris is widely used as a herbal medicine for cancers, inflammatory diseases, and other infections. Although it has long been used, few studies have examined its effects on central nervous system function. Here, we first observed that ethanolic extracts of P. vulgaris (EEPV) prolonged pentobarbital-induced sleep duration in mice. It is known that EEPV consists of many active components including triterpenoid (ursolic acid and oleanolic acid), which have many biological activities. Therefore, we evaluated which EEPV components induced sleep extension in pentobarbital-mediated sleeping model in mice. Surprisingly, despite their structural similarity and other common functions such as anti-inflammation, anti-cancer, and tissue protection, only ursolic acid enhanced sleep duration in pentobarbital-treated mice. These results were attenuated by bicuculline treatment, which is a GABAA receptor antagonist. The present results suggest that ursolic acid from P. vulgaris enhances sleep duration through GABAA receptor activation and could be a therapeutic candidate for insomnia treatment.

Ginseng in traditional herbal prescriptions.

Panax ginseng Meyer has been widely used as a tonic in traditional Korean, Chinese, and Japanese herbal medicines and in Western herbal preparations for thousands of years. In the past, ginseng was very rare and was considered to have mysterious powers. Today, the efficacy of drugs must be tested through well-designed clinical trials or meta-analyses, and ginseng is no exception. In the present review, we discuss the functions of ginseng described in historical documents and describe how these functions are taken into account in herbal prescriptions. We also discuss the findings of experimental pharmacological research on the functions of ginseng in ginseng-containing prescriptions and how these prescriptions have been applied in modern therapeutic interventions. The present review on the functions of ginseng in traditional prescriptions helps to demystify ginseng and, as a result, may contribute to expanding the use of ginseng or ginseng-containing prescriptions.

Schizandra chinensis and Scutellaria baicalensis counter stress behaviors in mice.

The individual and combined antistress effects of the fruit of Schizandra chinensis and the radix of Scutellaria baicalensis were evaluated using a mouse acute stress model. Stress consisted of immobilization and electric foot shocks over 5 days. Mice were treated with herbal extracts for 7 days before exposing the animals to stress. Before each stressor presentation, the mice were treated with each herbal extract. Reduced locomotor activity and the percentage of time spent in the open arms of an elevated plus-maze under stress were recovered by treatment with the extract containing equal amounts of S. chinensis and S. baicalensis (CB11) at 200 and 400 mg/kg (p < 0.05). The effects of CB11 were greater than the effects of S. chinensis or S. baicalensis alone. CB11 treatment (100, 200 and 400 mg/kg) significantly reduced serum corticosterone levels (p < 0.05). Spleen size and the serum interleukin-2 level decreases induced by stress were prevented by CB11 (200 mg/kg) (p < 0.05). Taken together, these results suggest that S. chinensis and S. baicalensis in equal amounts could be used to treat stress disorders, in part, by preventing corticosterone and IL-2 level changes and ameliorating stress-related behavior parameters.