scholarly journals Neuroprotective Effect of Ethanol Extract of Leaves of Malva parviflora against Amyloid-β- (Aβ-) Mediated Alzheimer’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Muhammad Aslam ◽  
Ali Akbar Sial
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Superoxide Dismutase ◽  
Water Maze ◽  
Neuroprotective Effect ◽  
Amyloid Β ◽  
Ethanol Extract ◽  
Neuroprotective Activity ◽  
Malva Parviflora ◽  
Lipid Peroxidase

Malva parviflora L. possesses significant antioxidant potential. This study was conducted to evaluate the neuroprotective effect of ethanol extract of the leaves of Malva parviflora against amyloid-β- (Aβ-) mediated Alzheimer’s disease. In Morris water maze model, the extract significantly restored the defected memory of amyloid-β injected mice (P<0.01). The reduced levels of brain antioxidant enzymes such as glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase were also restored significantly to similar levels as seen in normal control mice (P<0.01). The levels of lipid peroxidase were decreased significantly in treatment group mice when compared to Alzheimer group mice (P<0.01). So, this study showed that ethanol extract of the leaves of Malva parviflora possesses neuroprotective activity in mice.

Selective Secretase Targeting for Alzheimer’s Disease Therapy

2021 ◽  
pp. 1-17
Author(s):  
Alvaro Miranda ◽  
Enrique Montiel ◽  
Henning Ulrich ◽  
Cristian Paz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Plaques ◽  
Neuroprotective Activity ◽  
Amyloid Β Protein ◽  
Secretase Activity ◽  
Membrane Bound ◽  
Aβ Production ◽  
Bace 1

Alzheimer’s disease (AD) is associated with marked atrophy of the cerebral cortex and accumulation of amyloid plaques and neurofibrillary tangles. Amyloid plaques are formed by oligomers of amyloid-β (Aβ) in the brain, with a length of 42 and 40 amino acids. α-secretase cleaves amyloid-β protein precursor (AβPP) producing the membrane-bound fragment CTFα and the soluble fragment sAβPPα with neuroprotective activity; β-secretase produces membrane-bound fragment CTFβ and a soluble fragment sAβPPβ. After α-secretase cleavage of AβPP, γ-secretase cleaves CTFα to produce the cytoplasmic fragment AICD and P3 in the non-amyloidogenic pathway. CTFβ is cleaved by γ-secretase producing AICD as well as Aβ in amyloidogenic pathways. In the last years, the study of natural products and synthetic compounds, such as α-secretase activity enhancers, β-secretase inhibitors (BACE-1), and γ-secretase activity modulators, have been the focus of pharmaceuticals and researchers. Drugs were improved regarding solubility, blood-brain barrier penetration, selectivity, and potency decreasing Aβ42. In this regard, BACE-1 inhibitors, such as Atabecestat, NB-360, Umibecestat, PF-06751979, Verubecestat, LY2886721, Lanabecestat, LY2811376, and Elenbecestat, were submitted to phase I-III clinical trials. However, inhibition of Aβ production did not recover cognitive functions or reverse the disease. Novel strategies are being developed, aiming at a partial reduction of Aβ production, such as the development of γ-secretase modulators or α-secretase enhancers. Such therapeutic tools shall focus on slowing down or minimizing the progression of neuronal damage. Here, we summarize structures and the activities of the latest compounds designed for AD treatment, with remarkable in vitro, in vivo, and clinical phase activities.

Neuroprotective Activity of the Methanolic Extract of Indigofera aspalathoides against Scopalamine induced Alzheimer's Disease in Experimental Rats

2021 ◽  
pp. 5163-5168
Author(s):  
Rajaram C. ◽  
S. Nelson Kumar ◽  
S. S. Sheeba Tabassum ◽  
Manohar R. ◽  
Sumanjali C.
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Traditional Medicine ◽  
Methanolic Extract ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Neuroprotective Activity ◽  
Control Group ◽  
Histological Structure ◽  
Anticancer Activities

The plant Indigofera aspalathoides is a traditional medicine with tremendous therapeutic potential which finds it use in treatment of various ailments such as antibacterial, antioxidant, anti-inflammatory, antidiabetic, and anticancer activities. There are no reports that related to the use of this plant in treating patients with Alzheimer’s disease (AD). Hence present study was aimed to scientifically evaluate the neuroprotective effect of the methanolic extract of Indigofera aspalathoides against scopalamine induced Alzheimer’s disease in experimental rats using behavioral tests like elevated plus maze, Y-maze, and rota-rod tests. In addition to this, biochemical evaluation for acetylcholinesterase activity and histopathological evaluation of brain were done. The results suggests that methanolic extract Indigofera aspalathoides (200mg/kg B.wt and 400mg/kg B.wt) used in this study shows significant improvement of various behavioral parameters like locomotion, anxiety, memory, motor integrity and coordination etc when compared to control group. MEIA inhibited brain AChE enzyme, thereby elevating Ach concentration in brain homogenate and ultimately improved memory of rats. Further, more or less normal histological structure of the hippocampus and all amyloid plaques and neurofibrillary tangles that are formed under the influence of scopolamine disappeared in the rats pretreated with MEIA (200mg/kg B.wt and 400mg/kg B.wt). It can be concluded that our results strongly support the anti-Alzheimer’s potential of the methanolic extract of the plant I.aspalathoides and its use in traditional medicine.

scholarly journals Multiple-Coated PLGA Nanoparticles Loading Triptolide Attenuate Injury of a Cellular Model of Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Lu Jia ◽  
Xiao-qi Nie ◽  
Hong-ming Ji ◽  
Zhi-xiang Yuan ◽  
Rong-shan Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chinese Herb ◽  
Amyloid Β ◽  
Eutectic Mixture ◽  
Neuroprotective Activity ◽  
Brain Targeting ◽  
Cellular Model ◽  
Model Of Alzheimer’S Disease ◽  
Chitosan Hydrochloride

Alzheimer’s disease (AD) is the most common neurodegenerative disease, which is associated with extracellular deposition of amyloid-β proteins (Aβ). It has been reported that triptolide (TP), an immunosuppressive and anti-inflammatory agent extracted from a Chinese herb Tripterygium wilfordii, shows potential neuroprotective effects pertinent to AD. However, the clinical use of TP for AD could be hampered due to its high toxicity, instability, poor water solubility, and nonspecific biodistribution after administration. In this paper, we reported a kind of multiple-coated PLGA nanoparticle with the entrapment of TP and surface coated by chitosan hydrochloride, Tween-80, PEG20000, and borneol/mentholum eutectic mixture (MC-PLGA-TP-NP) as a novel nasal brain targeting preparation for the first time. The obtained MC-PLGA-TP-NP was 147.5 ± 20.7  nm with PDI of 0.263 ± 0.075 , zeta potential of 14.62 ± 2.47  mV, and the entrapment efficiency and loading efficiency of 93.14 % ± 4.75 % and 1.17 ± 0.08 % , respectively. In comparison of TP, MC-PLGA-TP-NP showed sustained-release profile and better transcellular permeability to Caco-2 cells in vitro. In addition, our data showed that MC-PLGA-TP-NP remarkably reduced the cytotoxicity, attenuated the oxidative stress, and inhibited the increase of the intracellular Ca2+ influx in differentiated PC12 cells induced by Aβ1-42. Therefore, it can be concluded that MC-PLGA-TP-NP is a promising preparation of TP, which exerts a better neuroprotective activity in the AD cellular model.

scholarly journals New Multitarget Hybrids Bearing Tacrine and Phenylbenzothiazole Motifs as Potential Drug Candidates for Alzheimer’s Disease

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 587 ◽  
Author(s):  
Rajeshwari Rajeshwari ◽  
Karam Chand ◽  
Emanuel Candeias ◽  
Sandra Cardoso ◽  
Sílvia Chaves ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroprotective Effect ◽  
Neuroblastoma Cells ◽  
Amyloid Β ◽  
Binding Mode ◽  
Docking Studies ◽  
Neuroprotective Effects ◽  
Drug Candidates ◽  
Ache Inhibitory Activity

Research on neurodegenerative brain disorders, namely the age-dependent Alzheimer’s disease (AD), has been intensified in the last decade due to the absence of a cure and the recognized increasing of life expectancy for populations. To address the multifactorial nature and complexity of AD, a multi-target-directed ligand approach was herein employed, by designing a set of six selected hybrids (14–19) that combine in the same entity two pharmacophores: tacrine (TAC) and 2-phenylbenzothiazole (PhBTA). The compounds contain a methoxy substituent at the PhBTA moiety and have a variable length linker between that and the TAC moiety. The docking studies showed that all the compounds assure a dual-binding mode of acetylcholinesterase (AChE) inhibition, establishing π-stacking and H-bond interactions with aminoacid residues at both active binding sites of the enzyme (CAS and PAS). The bioassays revealed that the designed compounds display excellent AChE inhibitory activity in the sub-micromolar range (0.06–0.27 μM) and moderate inhibition values for amyloid-β (Aβ) self-aggregation (27–44.6%), compounds 14 and 15 being the lead compounds. Regarding neuroprotective effects in neuroblastoma cells, compounds 15, 16 and 19 revealed the capacity to prevent Aβ-induced toxicity, but compound 16 showed the highest neuroprotective effect. Overall these hybrid compounds, in particular 15 and 16, with promising multitarget anti-AD ability, encourage further pursuing studies on this type of TAC-PhBTA derivatives for potential AD therapy.

scholarly journals Age-Related Transcriptional Deregulation of Genes Coding Synaptic Proteins in Alzheimer's Disease Murine Model: Potential Neuroprotective Effect of Fingolimod

2021 ◽  
Vol 14 ◽  
Author(s):  
Henryk Jęśko ◽  
Iga Wieczorek ◽  
Przemysław Leonard Wencel ◽  
Magdalena Gąssowska-Dobrowolska ◽  
Walter J. Lukiw ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroprotective Effect ◽  
Amyloid Β ◽  
Model Potential ◽  
Synaptic Proteins ◽  
Sphingolipid Metabolism ◽  
Neurofilament Light ◽  
Neuronal Phenotype ◽  
Age Related

Alzheimer's disease (AD) induces time-dependent changes in sphingolipid metabolism, which may affect transcription regulation and neuronal phenotype. We, therefore, analyzed the influence of age, amyloid β precursor protein (AβPP), and the clinically approved, bioavailable sphingosine-1-phosphate receptor modulator fingolimod (FTY720) on the expression of synaptic proteins. RNA was isolated, reverse-transcribed, and subjected to real-time PCR. Expression of mutant (V717I) AβPP led to few changes at 3 months of age but reduced multiple mRNA coding for synaptic proteins in a 12-month-old mouse brain. Complexin 1 (Cplx1), SNAP25 (Snap25), syntaxin 1A (Stx1a), neurexin 1 (Nrxn1), neurofilament light (Nefl), and synaptotagmin 1 (Syt1) in the hippocampus, and VAMP1 (Vamp1) and neurexin 1 (Nrxn1) in the cortex were all significantly reduced in 12-month-old mice. Post mortem AD samples from the human hippocampus and cortex displayed lower expression of VAMP, synapsin, neurofilament light (NF-L) and synaptophysin. The potentially neuroprotective FTY720 reversed most AβPP-induced changes in gene expression (Cplx1, Stx1a, Snap25, and Nrxn1) in the 12-month-old hippocampus, which is thought to be most sensitive to early neurotoxic insults, but it only restored Vamp1 in the cortex and had no influence in 3-month-old brains. Further study may reveal the potential usefulness of FTY720 in the modulation of deregulated neuronal phenotype in AD brains.

scholarly journals Pre-Clinical Neuroprotective Evidences and Plausible Mechanisms of Sulforaphane in Alzheimer’s Disease

2021 ◽  
Vol 22 (6) ◽  
pp. 2929
Author(s):  
Jiyoung Kim
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroprotective Effect ◽  
Amyloid Β ◽  
Autism Spectrum ◽  
Cruciferous Vegetables ◽  
Related Factor ◽  
Protective Effects ◽  
Carcinogenic Agent ◽  
Clinical Biomarkers

Sulforaphane, a potent dietary bioactive agent obtainable from cruciferous vegetables, has been extensively studied for its effects in disease prevention and therapy. Sulforaphane potently induces transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated expression of detoxification, anti-oxidation, and immune system-modulating enzymes, and possibly acts as an anti-carcinogenic agent. Several clinical trials are in progress to study the effect of diverse types of cruciferous vegetables and sulforaphane on prostate cancer, breast cancer, lung cancer, atopic asthmatics, skin aging, dermatitis, obesity, etc. Recently, the protective effects of sulforaphane on brain health were also considerably studied, where the studies have further extended to several neurological diseases, including Alzheimer’s disease (AD), Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, multiple sclerosis, autism spectrum disorder, and schizophrenia. Animal and cell studies that employ sulforaphane against memory impairment and AD-related pre-clinical biomarkers on amyloid-β, tau, inflammation, oxidative stress, and neurodegeneration are summarized, and plausible neuroprotective mechanisms of sulforaphane to help prevent AD are discussed. The increase in pre-clinical evidences consistently suggests that sulforaphane has a multi-faceted neuroprotective effect on AD pathophysiology. The anti-AD-like evidence of sulforaphane seen in cells and animals indicates the need to pursue sulforaphane research for relevant biomarkers in AD pre-symptomatic populations.

scholarly journals Potential Benefits of Nobiletin, A Citrus Flavonoid, against Alzheimer’s Disease and Parkinson’s Disease

2019 ◽  
Vol 20 (14) ◽  
pp. 3380 ◽  
Author(s):  
Akira Nakajima ◽  
Yasushi Ohizumi
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Neurodegenerative Disease ◽  
Cognitive Deficits ◽  
Amyloid Β ◽  
Neuroprotective Activity ◽  
Substantia Nigra Pars Compacta

Alzheimer’s disease (AD), which is characterized by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles, accompanied by neurodegeneration, is the most common form of age-related neurodegenerative disease. Parkinson’s disease (PD) is the second most common neurodegenerative disease after AD, and is characterized by early prominent loss of dopaminergic neurons in the substantia nigra pars compacta. As currently available treatments are not able to significantly alter the progression of these diseases, successful therapeutic and preventive interventions are strongly needed. In the course of our survey of substances from natural resources having anti-dementia and neuroprotective activity, we found nobiletin, a polymethoxylated flavone from the peel of Citrus depressa. Nobiletin improved cognitive deficits and the pathological features of AD, such as Aβ pathology, hyperphosphorylation of tau, and oxidative stress, in animal models of AD. In addition, nobiletin improved motor and cognitive deficits in PD animal models. These observations suggest that nobiletin has the potential to become a novel drug for the treatment and prevention of neurodegenerative diseases such as AD and PD.

scholarly journals Alzheimer's Disease Amyloid-β Binds Copper and Zinc to Generate an Allosterically Ordered Membrane-penetrating Structure Containing Superoxide Dismutase-like Subunits

2001 ◽  
Vol 276 (23) ◽  
pp. 20466-20473 ◽  
Author(s):  
Cyril C. Curtain ◽  
Feda Ali ◽  
Irene Volitakis ◽  
Robert A. Cherny ◽  
Raymond S. Norton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Superoxide Dismutase ◽  
Amyloid Β ◽  
Copper And Zinc

scholarly journals Neuroprotective Effects of Higenamine Against the Alzheimer’s Disease Via Amelioration of Cognitive Impairment, Aβ Burden, Apoptosis and Regulation of Akt/GSK3β Signaling Pathway

Dose-Response ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 155932582097220
Author(s):  
Xiaona Yang ◽  
Wanliang Du ◽  
Yun Zhang ◽  
Hui Wang ◽  
Maolin He
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Neuroprotective Effect ◽  
Amyloid Β ◽  
Control Group ◽  
Neuroprotective Effects ◽  
Learning Impairments ◽  
Oxidative Markers ◽  
Cervical Amputation

The present investigation was envisaged to elucidate the neuroprotective effect of Higenamine (HGN) against aluminum chloride (AlCl3) triggered experimental Alzheimer’s disease (AD) rat model. Thirty-six male albino Wister rats were randomized and divided in 6 groups and subjected to experimentation for 6 weeks. Control group, AlCl3 (100 mg/kg orally), HGN (50 mg/kg orally), HGN25, HGN50, HGN75 (HGN 25, 50 and 75 mg/kg respectively and AlCl3 100 mg/kg orally). After completion of 42 days protocol, the animals were subjected to passive avoidance test. The animals were then anesthetized by intramuscularly injecting ketamine hydrochloride (24 mg/kg body weight) and euthanized by cervical amputation. Cortical and hippocampal tissues were carefully removed and were employed for quantification of aluminum and acetylcholinesterase. The tissues were quantified using Western blotting and detection kits for APP, Aβ1-42, β and γ secretases, Bax, Bad, caspases-9, cyto-c, pAkt and pGSK-3β, and oxidative markers. HGN significantly protected AlCl3 induced memory and learning impairments, Al overload, AChE hyperactivity, amyloid β (Aβ) burden and apoptosis in brain tissues via activating Akt/GSK3β pathway. HGN attenuated oxidative damage induced by Al by modulation of oxidative markers. Our findings advocate the neuroprotective effect of HGN in AlCl3 induced AD rat model.

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