The effects of a standardized Acanthopanax koreanum extract on stress-induced behavioral alterations in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots and stem bark of Acanthopanax koreanum Nakai (Araliaceae), a well-known herbal medicine in Jeju Island, Korea, has been used as a tonic agent in treating stress-related states. Despite its popular application, the anti-anxiety or anti-depressive action of Acanthopanax koreanum is not yet known. AIM OF THE STUDY: This study aimed to determine the effects of Acanthopanax koreanum on stress-induced behavioral alterations such as anxiety and depression. MATERIALS AND METHODS: Mice in the acute stress group were exposed to immobilization stress for 2h followed by electric foot shocks (0.5 mA in 1 s duration with a 10 s inter-shock interval) for 2 min, while sub-chronically stressed mice were exposed to these stresses for 2 weeks, once per day. 70% ethanolic extract of Acanthopanax koreanum (EEAK) (25, 50, 100, or 200 mg/kg) was administered once or sub-chronically (for 2 weeks) 1h prior to stress induction. Anxiety- or depression-like behavioral changes were evaluated using the elevated plus-maze (EPM) test and the forced swimming test (FST) a day after the final stress induction. Corticosterone levels and spleen weight were measured after conducting all the behavioral assays. The numbers of BrdU- or DCX-immunopositive cells in the hippocampal region of sub-chronically stressed mice were measured 2 days after EEAK treatment. RESULTS: The percentage of time spent in the open arms was decreased in both the acutely and chronically stressed mice. In the FST, the immobility time was increased by only chronic stress, but not by acute stress. Acute or sub-chronic administration of EEAK significantly prevented the anxiety- or depression-like behavioral changes caused by stress. EEAK also attenuated stress-induced decrease and increase of spleen weight and corticosterone levels, respectively. Furthermore, the sub-chronic administration of EEAK (100 or 200 mg/kg, for 2 weeks) increased the number of BrdU-, doublecortin-, and neuropeptide Y-positive cells in the hippocampal region of the sub-chronically stressed mice. CONCLUSION: EEAK attenuated the behavioral and biochemical changes in acute or sub-chronic stressed mice. These results suggest the therapeutic potential of Acanthopanax koreanum for the treatment of stress-related neuropsychiatric disorders including anxiety disorders or major depressive disorder.

Neuroprotective effects of salvianolic acid B on an Aß25-35 peptide-induced mouse model of Alzheimer's disease.

Salvianolic acid B (SalB) is a polyphenolic compound found in Salvia miltiorrhiza Bunge that has several anti-oxidative and anti-inflammatory effects. In the present study, we investigated whether SalB has neuroprotective effects in an amyloid ß (Aß) peptide-induced Alzheimer's disease mouse model. Mice were injected with Aß25-35 peptide intracerebroventricularly and were subsequently administered SalB once daily for 7 days. Subchronic SalB administration (10mg/kg) significantly ameliorated the Aß25-35 peptide-induced memory impairment in the passive avoidance task (P<0.05). SalB treatment also reduced the number of activated microglia and astrocytes that were observed during the inflammatory reaction after the administration of the Aß25-35 peptide. Moreover, SalB markedly reduced inducible nitric oxide synthase and cyclooxygenase-2 expression levels and thiobarbituric acid reactive substances, which were increased by the administration of the Aß25-35 peptide. Furthermore, SalB administration significantly rescued the Aß25-35 peptide-induced decrease of choline acetyltransferase and brain-derived neurotrophic factor protein levels. These results suggest that SalB exerts neuroprotective activity via anti-inflammatory and anti-oxidative effects and that SalB may be a potential candidate for Alzheimer's disease therapy.

Prunella vulgaris attenuates prepulse inhibition deficit and attention disruption induced by MK-801 in mice.

Prunella vulgaris var. lilacina is widely distributed in Korea, Japan, China, and Europe, and it has been traditionally used to treat inflammation or hypertension. In the present study, we investigated the effects of the ethanolic extract of the spikes of Prunella vulgaris var. lilacina (EEPV) on dizocilpine (MK-801)-induced schizophrenia-like phenotype behaviors such as the disruption of prepulse inhibition and attention deficits in mice. We also determined the effect of EEPV on MK-801-induced alterations in phosphorylated extracellular signal-regulated kinase, phosphorylated protein kinase B, phospho-glycogen synthase kinase 3-ß, and phosphorylated cAMP response element-binding protein levels in the cortex and hippocampus of mice. MK-801-induced prepulse inhibition deficits were ameliorated by the administration of EEPV, as shown in the acoustic startle response test. Furthermore, EEPV attenuated the MK-801-induced attention deficits in the water finding test. We also found that EEPV attenuated the increased phosphorylated extracellular signal-regulated kinase, phosphorylated protein kinase B, or phospho-glycogen synthase kinase 3-ß levels induced by MK-801 in the cortex but not in the hippocampus. These results suggest that EEPV could be useful for treating schizophrenia because EEPV ameliorates prepulse inhibition disruption and attention deficits induced by MK-801.

The memory ameliorating effects of INM-176, an ethanolic extract of Angelica gigas, against scopolamine- or Aß(1-42)-induced cognitive dysfunction in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease is a neurodegenerative disorder associated with cognitive impairment and cholinergic neuronal death. INM-176 is a standardized ethanolic extract of Angelica gigas Nakai that has been traditionally used in herbal medicine in China, Japan, and Korea to treat anemia or as a sedative. We investigated whether INM-176 exhibits anti-amnesic effects. MATERIALS AND METHODS: Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist, or amyloid ß(1-42) (Aß(1-42)) protein. Anti-amnesic effects of INM-176 were measured by the passive avoidance and the Morris water maze tasks in mice. We also examined the effect of INM-176 on the acetylcholinesterase activity, as well as Aß(1-42) protein-induced astrogliosis or cholinergic neuronal loss in the brain. RESULTS: Scopolamine-induced cognitive dysfunction was significantly attenuated by a single or sub-chronic administration of INM-176 in the passive avoidance and the Morris water maze tasks. A single or sub-chronic administration of INM-176 also ameliorated memory impairments induced by Aß(1-42) protein. INM-176 inhibited acetylcholinesterase activity in the hippocampal tissue in vitro and ex vivo. In addition, INM-176 attenuated the Aß(1-42) protein-induced astrocyte activation in the hippocampus as well as cholinergic neuronal damage in the CA3 region of the hippocampus and the nucleus basalis of Meynert. CONCLUSION: These results suggest that the memory ameliorating effects of INM-176 on scopolamine- or Aß(1-42) protein-induced memory impairment are mediated, in part, via acetylcholinesterase inhibition and neuroprotective activities.

Neuroprotective effects of INM-176 against lipopolysaccharide-induced neuronal injury.

Neuroinflammation plays a critical role in the etiology of chronic neurodegenerative diseases such as Alzheimer's disease. INM-176 is a standardized ethanolic extract of Angelica gigas, which has been traditionally used as a tonic to treat anemia. In the present study, we investigated whether INM-176 exhibits neuroprotective activities against lipopolysaccharide (LPS)-induced neuronal damage in vitro and in vivo. In primary microglial cells, INM-176 significantly inhibited LPS-induced nitric oxide release and expression of tumor necrosis factor-α and interleukin-1ß. The expression levels of inducible nitric oxide synthase and cylcooxygenase-2 in BV2 microglial cells were markedly upregulated by LPS, but this increased expression was counteracted by INM-176. LPS-mediated neuronal damage in an organotypic hippocampal slice culture was also attenuated by the administration of INM-176. In addition, LPS (1 µg/2 µl, i.c.v.)-induced cognitive dysfunction in mice, as determined by passive avoidance and Y-maze tasks, was significantly attenuated by the administration of INM-176. Furthermore, the activation of microglia or astrocytes by LPS in the hippocampal regions of mice was suppressed by INM-176. These results suggest that the neuroprotective and cognition ameliorating effects of INM-176 against LPS-induced damage are mediated, in part, by its anti-inflammatory activities.