Beneficial Effects of Gagam-Palmultang on Scopolamine-Induced Memory Deficits in Mice

From text mining of Dongeuibogam, the 7 herbs in Palmultang can be considered effective candidates for memory enhancement. We sought to determine whether Gagam-Palmultang, comprising these 7 herbs, ameliorates scopolamine-induced memory impairment in mice, by focusing on the central cholinergic system and memory-related signaling molecules. Behavioral tests were performed after inducing memory impairment by scopolamine administration. The cholinergic system activity and memory-related molecules were examined in the hippocampus by enzyme-linked immunosorbent, western blot, and immunofluorescence assays. Gagam-Palmultang ameliorated scopolamine-induced memory impairment in the Morris water maze test, producing a significant improvement in the mean time required to find the hidden platform. Treatment with Gagam-Palmultang reduced acetylcholinesterase activity and expression in the hippocampus induced by scopolamine. The diminished phosphorylated phosphatidylinositide 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), and mature brain-derived neurotrophic factor (mBDNF) expressions caused by scopolamine administration were attenuated by treatment with Gagam-Palmultang. This treatment also promoted neuronal cell proliferation in the hippocampus. Gagam-Palmultang has beneficial effects against scopolamine-induced memory impairments, which are exerted via modulation of the cholinergic system as well as the PI3K and ERK/CREB/BDNF signaling pathway. Therefore, this multiherb formula may be a useful therapeutic agent for diseases associated with memory impairments

Neuroprotective Effects of <i>Sparassis crispa</i> Ethanol Extract through the AKT/NRF2 and ERK/CREB Pathway in Mouse Hippocampal Cells

Sparassis crispa, known as the “Cauliflower mushroom”, is an edible medicinal fungus found in Asia, Europe, and North America. Its fruiting bodies contain active biological and pharmacological ingredients with antitumor and anti-inflammatory properties. In this study, we investigated the neuroprotective effect of various Sparassis crispa extract against glutamate-induced toxicity and oxidative stress in hippocampal HT22 cells. Cell viability and reactive oxygen species (ROS) analyses served to evaluate the neuroprotective effects of Sparassis crispa ethanol extract (SCE) and their fractions partitioned with ethyl acetate (EtOAc; SCE-E) and water (SCE-W) in HT22 cells. SCE and SCE-E treatment reduced glutamate-induced cell death and ROS generation. SCE-E reduced apoptosis and ROS levels by regulating anti-apoptotic proteins. Under glutamate treatment, SCE-E activated nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and regulated extracellular signal-regulated kinase (ERK) and AKT signals at late stages. SCE-E increased the protein expression of cAMP response element binding (CREB), brain-derived neurotrophic factor (BDNF), and Kelch-like ECH-associated protein 1 (Keap1), and decreased the Nrf2 protein expression. Moreover, co-treatment of SCE-E and wortmannin did not activate Nrf2 expression. Thus, the neuroprotective effect of SCE-E is likely due to Nrf2 and CREB activation through AKT and ERK phosphorylation, which effectively suppress glutamate-induced oxidative stress in HT22 cells. Accordingly, a daily supplement of SCE-E could become a potential treatment for oxidative-stress-related neurological diseases

<i>Vaccinium bracteatum</i> Thunb Extract Inhibits HSV-1 Infection by Regulating ER Stress and Apoptosis

Herpes simplex Type 1 (HSV-1) is a neurotropic virus that infects the peripheral and central nervous system. Usually, after primary infection in epithelial cells, HSV-1 migrates retrograde to the peripheral nervous system (PNS), where it establishes a latent infection. HSV-1 can remain latent in the nervous system, and its reactivation in the brain can rarely cause acute HSV-1 encephalitis, often a life-threatening condition, or asymptomatic reactivations that could lead to neuronal damage and ultimately neurodegenerative disorders. Acyclovir and related nucleoside analogs have been used as therapeutic agents for HSV-1 infection, but resistance to the drug can arise, and the protective effect of HSV-1 on brain cells is limited. Therefore, there is an urgent need for research into safe and effective new antiviral agents that can protect brain cells from the damage that is caused by HSV-1 infection. Vaccinium bracteatum Thunb. (VBT) is widely distributed in Korea and China, and has pharmacological actions such as anti-inflammatory, antioxidant, and antidiabetic activity. Studies on the antiviral effect of VBT on HSV-1 infection have not been reported so far. Therefore, we sought to determine the HSV-1 antiviral effect and molecular mechanism of VBT at the cellular level. We confirmed that VBT repressed the VP16 and IE genes in both Vero and SK-N-SH cells. We also found that the generation of HSV-1 virions was inhibited by VBT treatment. VBT inhibited the activities of the HSV-1-induced endoplasmic reticulum (ER) stressors PERK, ATF4, and CHOP. We confirmed that VBT inhibited the activity of apoptosis factors by regulating the expression of death receptor (DR) after HSV-1 infection. As HSV-1 is closely associated with brain diseases, the study of the antiviral drug effects and mechanism of VBT is meaningful. Further studies using animal models of infection will also be performed to determine the potential of VBT as an antiviral agent

Anti-Neuroinflammatory Effects of the Human Milk Oligosaccharide, 2′-Fucosyllactose, Exerted via Modulation of M2 Microglial Activation in a Mouse Model of Ischemia–Reperfusion Injury

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2′-fucosyllactose (2′-FL), a human milk oligosaccharide, exerts anti-inflammatory effects and plays a protective role in arterial thrombosis; however, its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2′-FL and its potential mechanisms in a mouse model of ischemic stroke. Neurological score and behavior tests revealed that 2′-FL promoted the recovery of neurological deficits and motor function in middle cerebral artery occlusion (MCAO) mice, and that 2′FL led to a reduction in the size of cerebral infarct. Biochemical studies showed that administration of 2′-FL led to a reduction of reactive oxygen species (ROS)-related products in the brain of MCAO mice. 2′-FL upregulated IL-10 and downregulated TNF-α level. In addition, 2′-FL enhanced M2-type microglial polarization and upregulated CD206 expression at 7 days after MCAO. At 3 days after MCAO, 2′-FL increased IL-4 levels and activated STAT6. Our data show that 2′-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type microglial polarization in MCAO mice. These results demonstrate that 2′-FL is a potentially effective therapeutic agent for ischemic stroke