acteoside and Alzheimer-Disease

Amyloid β-protein (Aβ)-induced apoptosis and oxidative stress of human brain microvascular endothelial cells(BMECs) are contributors to the development of Alzheimer's disease (AD). Acteoside has shown its therapeutic potential for AD treatment. Therefore, this study investigated the effect of acteoside on Aβ-induced blood-brain barrier damage, oxidative stress and apoptosis as well as to explore the underlying mechanisms through network pharmacology.. The study used Aβ to induce human BMECs to construct an in-vitro injury model. Following treatment with acteoside, transendothelial electrical resistance (TEER), RT-qPCR and Western blot were used to evaluate the permeability of BMECs. The apoptosis level was detected by TUNEL and Western blot, ROS assay kit was used for the detection of reactive oxygen species (ROS) expression. The let-7g-5p expression level was detected by RT-qPCR. After additional treatment with let-7g-5p inhibitor, corresponding assays were performed again. Finally, network pharmacology was used to verify the mechanism.. Acteoside decreased the permeability, oxidative stress and cell apoptosis of Aβ-stimulated cells. More importantly, acteoside-activated let-7g-5p and additional treatment with let-7g-5p inhibitor abated the effects of acteoside on Aβ-induced permeability, oxidative stress and apoptosis of Aβ-stimulated BMECs. According to network pharmacology, 233 targeted genes of acteoside and 122 potential targets of let-7g-5p were determined by screening several databases, and two targets called Casp-3 and ITGB3 were obtained after taking the intersection.. In conclusion, these results reveal that acteoside-activated let-7g-5p attenuating Aβ-induced increased permeability and apoptosis of human BMECs.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Apoptosis; Brain; Endothelial Cells; Glucosides; Humans; MicroRNAs; Network Pharmacology; Permeability; Polyphenols; Reactive Oxygen Species

Alzheimer's disease (AD), a neurodegenerative disease, has been, by and large, correlated to insulin pathway, glucose level, and energy metabolism in the brain. Intracerebroventricular administration of streptozotocin (ICV-STZ) leads to glucose and energy metabolism dysfunction, cognitive impairment, and increased oxidative stress in the brain. Acteoside has a myriad of pharmacological effects on the brain, namely, neuroprotection and recuperation of cognitive functions. The primary focus of the current study was to examine the effect of acteoside on insulin, glucose transport, and energy metabolism in the hippocampal area of the brain. The behavioral experiments such as spatial memory, active learning, and passive memory suggested that acetoside ameliorated the ICV-STZ-induced learning and cognitive impairment. The acteoside induced increase in the protein expression of glucose transporters (Glu T1, Glu T3, and Glu T4), glucose, and insulin levels in the hippocampus for maintaining normal learning and memory function were demonstrated by Western blot. In addition, acteoside's long-term oral administration increased the the ratio of ATP content divided by ADP content (ATP/ADP) ratio, which, in turn, reduced the reactiveoxygen species (ROS) level and improved the cellular oxidative stress response. Compared with the model group, the above results show significant differences in different degrees (p < .05 or p < .01). This study suggests that acteoside can ameliorate the ICV-STZ-induced learning and memory impairment caused due to insulin receptor, insulin receptor substrate 1, Glu T1, Glu T3, and Glu T4 pathways by triggering intracerebral metabolism.

Topics: Alzheimer Disease; Animals; Brain; Cognition; Cognitive Dysfunction; Energy Metabolism; Glucose; Glucosides; Hippocampus; Insulin; Male; Maze Learning; Memory Disorders; Phenols; Rats; Rats, Sprague-Dawley; Receptor, Insulin; Streptozocin

Cistanche tubulosa is a precious traditional Chinese medicine that has been widely used in the treatment of osteoporosis and Alzheimer's disease. Echinacoside and acteoside are the main active constituents in Cistanche tubulosa that have the pharmacological activities with research value. It has been reported that echinacoside and acteoside could improve the learning and memory ability, promote the proliferation and differentiation of osteoblast.. Echinacoside and acteoside from Cistanche tubulosa have shown significant activities of anti-osteoporosis and anti-Alzheimer's disease, while these effects have not been studied concurrently in a rat model. The aim of this study was to establish and verify the model of osteoporosis combined with Alzheimer's disease in rat, and to investigate the double effects of echinacoside and acteoside on this concurrent model.. Compared with Sham group, OVX + D group could significantly reduce the learning and memory ability by causing oxidative damage, impairing neurons in hippocampus and affecting the hydrolysis and synthesis of acetylcholine. Meanwhile, the activities of BALP and TRAP in OVX + D group increased significantly (P < 0.001) as compared to Sham group. In addition, compared with Sham group, the mean bone mineral density obviously decreased (P < 0.05), the trabecular bone mass and microarchitecture were also destroyed significantly in OVX + D group. Furthermore, the maximum load and maximum stress significantly reduced (P < 0.01) and the energy absorption also decreased greatly as compared to Sham group. After administrated with echinacoside and acteoside, the typical pathological features of osteoporosis and Alzheimer's disease were ameliorated.. The model of osteoporosis combined with Alzheimer's disease in rat was feasible and successfully established. Echinacoside and acteoside also showed some significant effects on this concurrent model, and they could be potential candidates from Cistanche tubulosa with double effects for further study.

Topics: Alzheimer Disease; Animals; Bone Density; Bone Remodeling; Cancellous Bone; Cistanche; Estradiol; Female; Glucosides; Glycosides; Hippocampus; Osteoporosis; Ovariectomy; Phenols; Plant Extracts; Rats; Rats, Wistar; Spatial Memory; Uterus

The focus of this study was on inhibition of enzymes involved in the pathogenesis Alzheimer's disease (AD) including prime amyloid beta (Aβ) producing enzyme (β-secretase: BACE-1) and disease progression enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), histone deacetylase (HDAC), and tyrosinase along with the catecholamine L-DOPA, by using olive biophenols. Here we report the strongest inhibition of BACE-1 from rutin (IC. Acetylthiocholine iodide (PubChem CID: 74629); S-Butyrylthiocholine chloride (PubChem CID: 3015121); Caffeic acid (PubChem CID: 689043); Dimethyl sulfoxide (DMSO) (PubChem: 679); L-3,4-Dihydroxyphenylalanine (L-DOPA) (PubChem CID: 6047); 5,5'-Dithiobis (2-nitrobenzoic acid) (DTNB) (PubChem CID: 6254); Epigallocatechin gallate (EGCG) (PubChem CID: 65064); Ethylenediamine tetraacetic acid (EDTA) (PubChem CID: 6049); Galantamine hydrobromide (PubChem CID: 121587); l-Glutamine (PubChem CID: 5961); Hydroxytyrosol (PubChem CID: 82755); Kojic acid (PubChem CID: 3840); Luteolin (PubChem CID: 5280445); Oleuropein (PubChem CID: 5281544); Penicillin-streptomycin (PubChem CID: 131715954); Quercetin (PubChem CID: 5280343); Rutin (PubChem CID: 5280805); Tris-HCl buffer (PubChem: 93573); Trypan blue (PubChem: 9562061).

Topics: Alzheimer Disease; Amyloid Precursor Protein Secretases; Cell Line, Tumor; Cholinesterase Inhibitors; Enzyme Inhibitors; Fruit; Glucosides; Histone Deacetylase Inhibitors; Humans; Monophenol Monooxygenase; Neuroprotective Agents; Olea; Oxidative Stress; Phenols; Quercetin; Rutin

Acteoside (verbascoside), a phenylethanoid glycoside widely distributed in various plants, has been shown to have potential activity against Alzheimer's disease, attracting great attentions recently. The present study was designed to develop a selective and sensitive LC-MS/MS method for the determination of acteoside in biological samples and carry our a pharmacokinetic (PK) study in beagle dogs. The PK parameters were calculated using non-compartmental models. Following a single-dose oral administration, acteoside was rapidly absorbed and eliminated, with Tmax being between 30 to 45 min and terminal half-life being about 90 min. The areas under the time-concentration curve (AUC) were 47.28 ± 8.74, 87.86 ± 13.33, and 183.14 ± 28.69 mg · min · L(-1) for oral administration of 10, 20, and 40 mg · kg(-1), respectively, demonstrating that the exposure of acteoside proportionally increased with the dose level. The absolute bioavailability of acteoside was around 4%. For all the PK parameters, there were large variations between individual dogs. In conclusion, the pharmacokinetic characteristics observed in the present study can be of great value to help better understand the pharmacological properties of acteoside and to improve the outcome of its clinical use.

Topics: Administration, Intravenous; Administration, Oral; Alzheimer Disease; Animals; Area Under Curve; Biological Availability; Chromatography, High Pressure Liquid; Dogs; Female; Glucosides; Intestinal Absorption; Male; Phenols; Plant Extracts; Tandem Mass Spectrometry; Verbenaceae

We examined the effects of acteoside (1a), which was isolated from Orobanche minor, and its derivatives on the aggregation of a 42-mer amyloid β protein (Aβ42) in our search for anti-amyloidogenic compounds for Alzheimer's disease (AD) therapy. Acteoside (1a) strongly inhibited the aggregation of Aβ42 in a dose-dependent manner. The structure-activity relationship for acteoside (1a) and related compounds suggests the catechol moiety of phenylethanoid glycosides to be essential for this inhibitory activity.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Catechols; Dose-Response Relationship, Drug; Glucosides; Humans; Orobanche; Peptide Fragments; Phenols; Plant Extracts; Structure-Activity Relationship

To investigate the effect of acteoside on SK-N-SH nerve cell injury induced by okadaic acid (OA).. SK-N-SH nerve cells were processed with 20 nmol * L OA to establish the Alzheimer's disease (AD) cellular model, and 5, 10, 20 mg . L-1 acteoside was used to antagonize against its effect. Cell morphology was observed under inverted microscope. The cell survival rate was detected with MTT, and the LDH release rate was measured by enzyme label kit. Western blot was applied to determine the expression of phosphorylation tau proteins in nerve cells.. The acteoside could significantly improve SK-N-SH cell morphology, enhance the cell survival rate, decrease the cell LDH release rate and the expression of phosphorylated tau proteins at p-Ser 199/202 and p-Ser 404 sites, up-regulated the expression of at non-phosphorylated tau proteins at Ser 202 site and Ser 404 sites.. Acteoside has significant protective effect on nerve cell injury induced by OA.

Topics: Alzheimer Disease; Cell Line; Cell Survival; Glucosides; Humans; Okadaic Acid; Phenols; tau Proteins

Amyloid beta-peptide (Abeta) has been implicated in the pathogenesis of AD. It can cause cell death in AD by evoking a cascade of oxidative damage to neurons. So antioxidant compounds may throw a light on the treatment of AD. In the present study, we investigated the protective effect of acteoside (AS), an antioxidative phenylethanoid glycoside, on Abeta(25-35)-induced SH-SY5Y cell injury. Exposure of cells to 25 muM Abeta(25-35) for 24 h caused viability loss, apoptotic increase and reactive oxygen species (ROS) increase, pre-treatment with acteoside for 1.5 h significantly reduced the viability loss, apoptotic rate and attenuated Abeta-mediated ROS production. In addition, AS strikingly inhibited Abeta(25-35)-induced mitochondrial dysfunctions, including lowered membrane potential, increased Bax/Bcl-2 ratio, cytochrome c release and the cleavage of caspase-3. Taken together, these results indicated that acteoside could protect SH-SY5Y cells against beta-amyloid-induced cell injury by the attenuating ROS production and the modulating apoptotic signal pathway through Bcl-2 family, cytochrome c, and caspase-3.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Caspase 3; Cell Line, Tumor; Cell Survival; Cytochromes c; Glucosides; Humans; Membrane Potential, Mitochondrial; Nerve Degeneration; Neurons; Neuroprotective Agents; Oxidative Stress; Peptide Fragments; Phenols; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species