Background Endoplasmic reticulum (ER) stress is involved in the progression of Alzheimer’s disease (AD). Verbascoside (VB), an active phenylethanoid glycoside that was first isolated from Verbascum sinuatum (the wavyleaf mullein), possesses anti-inflammatory, antioxidative, and anti-apoptotic effects. The purpose of this study was to elucidate the beneficial effects of VB in amyloid β (Aβ)1–42-damaged human glioma (U251) cells and in APPswe/PSEN1dE9 transgenic (APP/PS1) mice. Methods U251 cells were co-incubated with 10 μM of Aβ1-42 and treated with VB. The protective effects of VB were investigated by using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay, flow cytometry, fluorescence staining, and transmission electron microscopy. APP/PS1 transgenic mice were treated for 6 weeks with VB. Learning and memory were evaluated using a Morris water maze test. Immunohistochemistry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, thioflavin-S staining, and proteomics analysis were performed to study the potential neuroprotective mechanism. Enzyme-linked immunosorbent assays and western blot were performed to analyze altered protein levels of brain lysates in APP/PS1 mice and/or Aβ1-42-damaged U251 cells. Results In Aβ1-42-damaged U251 cells, VB significantly improved cell viability, inhibited apoptosis, reduced calcium accumulation and the intracellular concentrations of reactive oxygen species, and improved the morphology of mitochondria and ER. In APP/PS1 mice, 6-week administration of VB significantly improved memory and cognition. VB inhibited apoptosis, reduced the deposition of Aβ, reduced the formation of neurofibrillary tangles formed by hyperphosphorylated tau protein, and downregulated the expression levels of 4-hydroxynonenal and mesencephalic astrocyte-derived neurotrophic factor in the brains of APP/PS1 mice. Proteomics analysis of mouse hippocampus suggested that the neuroprotective effect of VB may be related to the reduction of ER stress. This was indicated by the fact that VB inhibited the three branches of the unfolded protein response, thereby attenuating ER stress and preventing apoptosis. Conclusions The results confirmed that VB possesses significant neuroprotective effects, which are related to the reduction of ER stress. These findings support the status of VB as a potentially effective treatment for AD and warrant further research.
Background Neuroinflammation is a principal element in Alzheimer’s disease (AD) pathogenesis, so anti-inflammation may be a promising therapeutic strategy. Forsythoside B (FTS•B), a phenylethanoid glycoside isolated from Forsythiae fructus, has been reported to exert anti-inflammatory effects. However, no studies have reported whether the anti-inflammatory properties of FTS•B have a neuroprotective effect in AD. In the present study, these effects of FTS•B were investigated using amyloid precursor protein/presenilin 1 (APP/PS1) mice, BV-2 cells, and HT22 cells. Methods APP/PS1 mice were administered FTS•B intragastrically for 36 days. Behavioral tests were then carried out to examine cognitive functions, including the Morris water maze, Y maze, and open field experiment. Immunohistochemistry was used to analyze the deposition of amyloid-beta (Aβ), the phosphorylation of tau protein, and the levels of 4-hydroxynonenal, glial fibrillary acidic protein, and ionized calcium-binding adapter molecule 1 in the hippocampus. Proteins that showed marked changes in levels related to neuroinflammation were identified using proteomics and verified using enzyme-linked immunosorbent assay and western blot. BV-2 and HT22 cells were also used to confirm the anti-neuroinflammatory effects of FTS•B. Results In APP/PS1 mice, FTS•B counteracted cognitive decline, ameliorated the deposition of Aβ and the phosphorylation of tau protein, and attenuated the activation of microglia and astrocytes in the cortex and hippocampus. FTS•B affected vital signaling, particularly by decreasing the activation of JNK-interacting protein 3/C-Jun NH2-terminal kinase and suppressing WD-repeat and FYVE-domain-containing protein 1/toll-like receptor 3 (WDFY1/TLR3), further suppressing the activation of nuclear factor-κB (NF-κB) signaling. In BV-2 and HT22 cells, FTS•B prevented lipopolysaccharide-induced neuroinflammation and reduced the microglia-mediated neurotoxicity. Conclusions FTS•B effectively counteracted cognitive decline by regulating neuroinflammation via NF-κB signaling in APP/PS1 mice, providing preliminary experimental evidence that FTS•B is a promising therapeutic agent in AD treatment.
BackgroundAlzheimer’s disease (AD) is a type of progressive neurodegenerative disease related to neuroinflammation. Forsythoside B (FTS•B), a phenylethanoid glycoside isolated from plants, has been reported to exert various pharmacological effects. However, the neuroprotection of FTS•B related to neuroinflammation has not been systemically reported.MethodsIn amyloid precursor protein/presenilin 1 (APP/PS1) mice, behavioral tests including Morris water maze, Y maze and open field experiment were used to examine the cognitive function. Immunohistochemistry were used to analyze amyloid-beta (Aβ) deposition, Tau protein phosphorylation, the levels of 4-hydroxynonenal (4-HNE), glial fibrillary acidic protein (GFAP) and ionized calcium binding adapter molecule 1 (Iba1). Remarkably changed proteins related to neuroinflammation were filtered via proteomics and verified via enzyme-linked immunosorbent assay (ELISA) and western blot. Besides, BV-2 cells and HT22 cells were used to confirm the anti-neuroinflammation of FTS·B.ResultsFTS·B counteracted cognitive decline, ameliorated Aβ deposition and Tau protein phosphorylation, attenuated microglia and astrocytes activation in the cortex and/or hippocampus. Furthermore, FTS·B affected vital signaling, particularly by decreasing the activation of JNK-interacting protein 3/C-Jun NH2-terminal kinase (JIP3/JNK) and suppressing WD-repeat and FYVE-domain-containing protein 1/toll-like receptor 3 (WDFY1/TLR3), further suppressing the activation of nuclear factor-κB (NF-κB) signaling. In BV-2 and HT22 cells, FTS·B prevented lipopolysaccharide (LPS)-induced neuroinflammation and reduced the microglia-mediated neurotoxicity.ConclusionsFTS·B counteracted cognitive decline by triggering neurogenesis via signaling associated with inflammation, suggesting the promising therapeutic effects of FTS·B on AD treatment.# The two authors contribute equally to the project
Aim: The primary objective of this study was to evaluate the effects of polypeptide-enriched Gastrodia elata extracts (GE) on vulvovaginal candidiasis (VVC). Materials & methods: A VVC model induced by Candida albicans ( C. albicans) infection was successfully developed in BALB/c mice. After treatment, the colony-forming unit (CFU) of vaginal lavage was measured by plating. The extent of the inflammatory response was assessed by hematoxylin-eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA). Results: GE had an inhibitory effect on the proliferation of C. albicans and inflammatory reaction. Meanwhile, it had a potentially beneficial effect on the growth of Lactobacillus. Conclusion: These results showed the potential application of GE as an antifungal agent in VVC treatment.
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