Dataset Information

Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease.

ABSTRACT: Due to its complex pathogenesis, the prevention and therapization of Alzheimer's disease (AD) remains a serious challenge. Crocin, the main compound isolated from Crocus sativus L., demonstrates various pharmacological activities including anti?apoptotic properties. The present study investigated the neuroprotective effect of crocin and the underlying mechanisms. In l?glutamate?damaged HT22 cells, 3?h crocin pretreatment strongly enhanced the HT22 cell viability, reduced the apoptotic rate, mitigated mitochondrial dysfunction, suppressed intracellular reactive oxygen species (ROS) accumulation and Ca2+ overload compared with untreated cells. Additionally, crocin significantly decreased the expression levels of Bax, Bad and cleaved caspase?3 and increased the expression levels of B?cell lymphoma?extra large, phosphorylated (P?) protein kinase B and P?mammalian target of rapamycin compared with untreated cells. In mice with AD induced by d?galactose and aluminum trichloride, crocin substantially improved the cognition and memory abilities of the mice as measured by their coordination of movement in an open field test, and reduced their escape time in the Morris water maze test compared with untreated mice. Biochemical analysis confirmed that crocin was able to reduce the A?1?42 content in the mouse brains, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase, and reduce the levels of ROS and acetylcholinesterase in the serum, cerebral cortex and hypothalamus compared with untreated mice. Immunohistochemical analysis demonstrated that crocin reduced A?1?42 deposition in the hippocampus of the brains of treated mice compared with untreated mice. In conclusion, crocin demonstrates good prospects in the treatment of AD through the oxidative stress?associated apoptosis signaling pathway.

SUBMITTER: Wang C

PROVIDER: S-EPMC6317678 | biostudies-other | 2019 Feb

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease.

Wang Chunyue C Cai Xueying X Hu Wenji W Li Zhiping Z Kong Fange F Chen Xia X Wang Di D

International journal of molecular medicine 20181218 2

Due to its complex pathogenesis, the prevention and therapization of Alzheimer's disease (AD) remains a serious challenge. Crocin, the main compound isolated from Crocus sativus L., demonstrates various pharmacological activities including anti‑apoptotic properties. The present study investigated the neuroprotective effect of crocin and the underlying mechanisms. In l‑glutamate‑damaged HT22 cells, 3‑h crocin pretreatment strongly enhanced the HT22 cell viability, reduced the apoptotic rate, miti ...[more]

PMID: 30569175

Similar Datasets

Project description: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 ? (A?)1-42-damaged human glioma (U251) cells and in APPswe/PSEN1dE9 transgenic (APP/PS1) mice. METHODS:U251 cells were co-incubated with 10 ?M of A?1-42 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 A?1-42-damaged U251 cells. RESULTS:In A?1-42-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 A?, 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.

Project description:Alzheimer's disease (AD) is the most common type of dementia and is characterized by advanced cognitive deterioration, deposition of Aβ (amyloid-beta), and the formation of neurofibrillary tangles. Administration of streptozotocin (STZ) via the intracerebroventricular (ICV) route is a reliable model resembling sporadic AD (SAD) associated neuropathological changes. The present study was undertaken to explore the neuroprotective effects of the methoxy flavonoid, umuhengerin, in an STZ-induced SAD mouse model as a potential therapy for AD. Mice were injected once with STZ (3 mg/kg, ICV), followed by daily administration of umuhengerin (orally, 30 mg/kg) or the positive control donepezil (orally, 2.5 mg/kg) for 21 days. The pharmacological activity of umuhengerin was assessed through estimation of oxidative stress and inflammatory markers via mouse ELISA kits, Western blot analysis, and brain histopathological examination. Morris water maze test was also conducted to investigate umuhengerin-induced cognitive enhancement. The results showed that umuhengerin attenuated STZ-produced neuroinflammation and oxidative stress with a notable rise in the expression of Nrf2 (nuclear factor erythroid 2-related factor 2). In contrast, it downregulated Keap-1 (Kelch-like ECH associated protein 1), as well as elevated brain contents of GSH (reduced glutathione) and HO-1 (heme oxygenase-1). STZ-injected animals receiving umuhengerin showed marked downregulation of the nuclear factor kappa beta (NF-Kβp65) and noticeable increment in the expression of its inhibitor kappa beta alpha protein (IKβα), as well as prominent reduction in malondialdehyde (MDA), H2O2 (hydrogen peroxide), and TNF-α (tumor-necrosis factor-alpha) contents. Β-secretase protein expression and acetylcholinesterase (AchE) activity were also diminished upon umuhengerin injection in the STZ group, leading to decreased Aβ formation and cognitive improvement, respectively. In conclusion, umuhengerin neuroprotective effects were comparable to the standard drug donepezil; thus, it could be an alternative approach for AD management.

Project description:The leaf extract of Tamarindus indica L. (T. indica) had been reported to possess high phenolic content and showed high antioxidant activities. In this study, the effects of the antioxidant-rich leaf extract of the T. indica on lipid peroxidation, antioxidant enzyme activities, H2O2-induced ROS production and gene expression patterns were investigated in liver HepG2 cells. Lipid peroxidation and ROS production were inhibited and the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase was enhanced when the cells were treated with the antioxidant-rich leaf extract. cDNA microarray analysis revealed that 207 genes were significantly regulated by at least 1.5-fold (p < 0.05) in cells treated with the antioxidant-rich leaf extract. The expression of KNG1, SERPINC1, SERPIND1, SERPINE1, FGG, FGA, MVK, DHCR24, CYP24A1, ALDH6A1, EPHX1 and LEAP2 were amongst the highly regulated. When the significantly regulated genes were analyzed using Ingenuity Pathway Analysis software, "Lipid Metabolism, Small Molecule Biochemistry, Hematological Disease" was the top biological network affected by the leaf extract, with a score of 36. The top predicted canonical pathway affected by the leaf extract was the coagulation system (P < 2.80 × 10(-6)) followed by the superpathway of cholesterol biosynthesis (P < 2.17 × 10(-4)), intrinsic prothrombin pathway (P < 2.92 × 10(-4)), Immune Protection/Antimicrobial Response (P < 2.28 × 10(-3)) and xenobiotic metabolism signaling (P < 2.41 × 10(-3)). The antioxidant-rich leaf extract of T. indica also altered the expression of proteins that are involved in the Coagulation System and the Intrinsic Prothrombin Activation Pathway (KNG1, SERPINE1, FGG), Superpathway of Cholesterol Biosynthesis (MVK), Immune protection/antimicrobial response (IFNGR1, LEAP2, ANXA3 and MX1) and Xenobiotic Metabolism Signaling (ALDH6A1, ADH6). In conclusion, the antioxidant-rich leaf extract of T. indica inhibited lipid peroxidation and ROS production, enhanced antioxidant enzyme activities and significantly regulated the expression of genes and proteins involved with consequential impact on the coagulation system, cholesterol biosynthesis, xenobiotic metabolism signaling and antimicrobial response.

Dataset Information

Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease.

Publications

Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure