Methanolic extract of Tamarix Gallica attenuates hyperhomocysteinemia induced AD-like pathology and cognitive impairments in rats

Although few drugs are available today for the management of Alzheimer’s disease (AD) and many plants and their extracts are extensively employed in animals’ studies and AD patients, yet no drug or plant extract is able to reverse AD symptoms adequately. In the present study, Tamarix gallica (TG), a naturally occurring plant known for its strong antioxidative, anti-inflammatory and anti-amyloidogenic properties, was evaluated on homocysteine (Hcy) induced AD-like pathology and cognitive impairments in rats. We found that TG attenuated Hcy-induced oxidative stress and memory deficits. TG also improved neurodegeneration and neuroinflammation by upregulating synaptic proteins such as PSD95 and synapsin 1 and downregulating inflammatory markers including CD68 and GFAP with concomitant decrease in proinflammatory mediators interlukin-1β (IL1β) and tumor necrosis factor α (TNFα). TG attenuated tau hyperphosphorylation at multiple AD-related sites through decreasing some kinases and increasing phosphatase activities. Moreover, TG rescued amyloid-β (Aβ) pathology through downregulating BACE1. Our data for the first time provide evidence that TG attenuates Hcy-induced AD-like pathological changes and cognitive impairments, making TG a promising candidate for the treatment of AD-associated pathological changes.

[1]  N. Tyagi,et al.  High methionine, low folate and low vitamin B6/B12 (HM-LF-LV) diet causes neurodegeneration and subsequent short-term memory loss , 2018, Metabolic brain disease.

[2]  M. Adamkov,et al.  Association of Induced Hyperhomocysteinemia with Alzheimer’s Disease-Like Neurodegeneration in Rat Cortical Neurons After Global Ischemia-Reperfusion Injury , 2018, Neurochemical Research.

[3]  E. D. Kirby,et al.  A Larger Social Network Enhances Novel Object Location Memory and Reduces Hippocampal Microgliosis in Aged Mice , 2018, Front. Aging Neurosci..

[4]  Jian-Zhi Wang,et al.  Moringa Oleifera Alleviates Homocysteine-Induced Alzheimer’s Disease-Like Pathology and Cognitive Impairments , 2018, Journal of Alzheimer's disease : JAD.

[5]  S. Haggarty,et al.  Inhibition of p25/Cdk5 Attenuates Tauopathy in Mouse and iPSC Models of Frontotemporal Dementia , 2017, The Journal of Neuroscience.

[6]  Guowei Huang,et al.  Homocysteine exaggerates microglia activation and neuroinflammation through microglia localized STAT3 overactivation following ischemic stroke , 2017, Journal of Neuroinflammation.

[7]  H. Isoda,et al.  Inhibitory Activities of Antioxidant Flavonoids from Tamarix gallica on Amyloid Aggregation Related to Alzheimer's and Type 2 Diabetes Diseases. , 2017, Biological & pharmaceutical bulletin.

[8]  Shengdi Chen,et al.  Oxidative stress: A major pathogenesis and potential therapeutic target of antioxidative agents in Parkinson’s disease and Alzheimer’s disease , 2016, Progress in Neurobiology.

[9]  S. Antonov,et al.  GluN2A Subunit-Containing NMDA Receptors Are the Preferential Neuronal Targets of Homocysteine , 2016, Front. Cell. Neurosci..

[10]  Jingwei Tian,et al.  (-)-SCR1693 Protects against Memory Impairment and Hippocampal Damage in a Chronic Cerebral Hypoperfusion Rat Model , 2016, Scientific Reports.

[11]  L. Luo,et al.  A novel acetylcholinesterase inhibitor and calcium channel blocker SCR-1693 improves Aβ25–35-impaired mouse cognitive function , 2016, Psychopharmacology.

[12]  K. Mccully Homocysteine Metabolism, Atherosclerosis, and Diseases of Aging. , 2015, Comprehensive Physiology.

[13]  N. Inestrosa,et al.  Is L-methionine a trigger factor for Alzheimer’s-like neurodegeneration?: Changes in Aβ oligomers, tau phosphorylation, synaptic proteins, Wnt signaling and behavioral impairment in wild-type mice , 2015, Molecular Neurodegeneration.

[14]  Anupom Borah,et al.  Activation of NMDA receptor by elevated homocysteine in chronic liver disease contributes to encephalopathy. , 2015, Medical hypotheses.

[15]  Q. Tian,et al.  A novel tacrine-dihydropyridine hybrid (-)SCR1693 induces tau dephosphorylation and inhibits Aβ generation in cells. , 2015, European journal of pharmacology.

[16]  K. Ishiguro,et al.  Physiological and pathological phosphorylation of tau by Cdk5 , 2014, Front. Mol. Neurosci..

[17]  S. Merali,et al.  Homocysteine exacerbates β‐amyloid pathology, tau pathology, and cognitive deficit in a mouse model of Alzheimer disease with plaques and tangles , 2014, Annals of neurology.

[18]  D. Fayuk,et al.  The role of NMDA and mGluR5 receptors in calcium mobilization and neurotoxicity of homocysteine in trigeminal and cortical neurons and glial cells , 2014, Journal of neurochemistry.

[19]  Xiongwei Zhu,et al.  Phosphorylation of Tau Protein as the Link between Oxidative Stress, Mitochondrial Dysfunction, and Connectivity Failure: Implications for Alzheimer's Disease , 2013, Oxidative medicine and cellular longevity.

[20]  Jian-Zhi Wang,et al.  Cleavage of GSK‐3β by calpain counteracts the inhibitory effect of Ser9 phosphorylation on GSK‐3β activity induced by H2O2 , 2013, Journal of Neurochemistry.

[21]  C. Abdelly,et al.  Anticancer effect of Tamarix gallica extracts on human colon cancer cells involves Erk1/2 and p38 action on G2/M cell cycle arrest , 2013, Cytotechnology.

[22]  H. Isoda,et al.  Inhibition of Amyloid β Aggregation by Acteoside, a Phenylethanoid Glycoside , 2013, Bioscience, biotechnology, and biochemistry.

[23]  K. Irie,et al.  Site-specific Inhibitory Mechanism for Amyloid β42 Aggregation by Catechol-type Flavonoids Targeting the Lys Residues* , 2013, Journal of Biological Chemistry.

[24]  Charles D. Smith,et al.  Induction of Hyperhomocysteinemia Models Vascular Dementia by Induction of Cerebral Microhemorrhages and Neuroinflammation , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[25]  M. Sharma,et al.  Antioxidant Activity, Total Phenolic, And Flavonoid Content Of Aerial Parts Of Tamarix Gallica , 2012 .

[26]  F. Checler,et al.  BACE1 is at the crossroad of a toxic vicious cycle involving cellular stress and β-amyloid production in Alzheimer’s disease , 2012, Molecular Neurodegeneration.

[27]  H. Isoda,et al.  Protective effects of caffeoylquinic acids on the aggregation and neurotoxicity of the 42-residue amyloid β-protein. , 2012, Bioorganic & Medicinal Chemistry.

[28]  J. Drazen Transparency for clinical trials--the TEST Act. , 2012, The New England journal of medicine.

[29]  N. Greig,et al.  TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation , 2012, Journal of Neuroinflammation.

[30]  F. LaFerla,et al.  Blocking IL-1 Signaling Rescues Cognition, Attenuates Tau Pathology, and Restores Neuronal β-Catenin Pathway Function in an Alzheimer’s Disease Model , 2011, The Journal of Immunology.

[31]  L. Tsai,et al.  Synaptic Deficits Are Rescued in the p25/Cdk5 Model of Neurodegeneration by the Reduction of β-Secretase (BACE1) , 2011, Journal of Neuroscience.

[32]  Richard E. White,et al.  The role of N-methyl-D-aspartate receptor activation in homocysteine-induced death of retinal ganglion cells. , 2011, Investigative ophthalmology & visual science.

[33]  R. Mayeux,et al.  Epidemiology of Alzheimer disease , 2011, Nature Reviews Neurology.

[34]  Richard Mooney,et al.  Rapid spine stabilization and synaptic enhancement at the onset of behavioural learning , 2010, Nature.

[35]  W. Gordon-Krajcer,et al.  Homocysteine-induced acute excitotoxicity in cerebellar granule cells in vitro is accompanied by PP2A-mediated dephosphorylation of tau , 2009, Neurochemistry International.

[36]  Jia-min Zhuo,et al.  Diet-induced hyperhomocysteinemia increases amyloid-beta formation and deposition in a mouse model of Alzheimer's disease. , 2009, Current Alzheimer research.

[37]  C. Abdelly,et al.  Antioxidant and antimicrobial activities of the edible medicinal halophyte Tamarix gallica L. and related polyphenolic constituents. , 2009, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[38]  Surojit Paul,et al.  Homocysteine–NMDA receptor‐mediated activation of extracellular signal‐regulated kinase leads to neuronal cell death , 2009, Journal of neurochemistry.

[39]  B. Ossola,et al.  The multiple faces of quercetin in neuroprotection , 2009, Expert opinion on drug safety.

[40]  Q. Tian,et al.  Hyperhomocysteinemia increases beta-amyloid by enhancing expression of gamma-secretase and phosphorylation of amyloid precursor protein in rat brain. , 2009, The American journal of pathology.

[41]  E. Head Oxidative Damage and Cognitive Dysfunction: Antioxidant Treatments to Promote Healthy Brain Aging , 2009, Neurochemical Research.

[42]  Hangyuan Guo,et al.  Influence of folic acid on plasma homocysteine levels & arterial endothelial function in patients with unstable angina. , 2009, The Indian journal of medical research.

[43]  Ahmed Bensatal,et al.  Inhibition of crystallization of calcium oxalate by the extraction of Tamarix gallica L , 2008, Urological Research.

[44]  S. Bischoff Quercetin: potentials in the prevention and therapy of disease , 2008, Current opinion in clinical nutrition and metabolic care.

[45]  V. Lučić,et al.  Detailed state model of CaMKII activation and autophosphorylation , 2008, European Biophysics Journal.

[46]  R. V. van Marum,et al.  Current and future therapy in Alzheimer’s disease , 2008, Fundamental & clinical pharmacology.

[47]  I. Grundke‐Iqbal,et al.  Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration , 2007, The European journal of neuroscience.

[48]  M. Pappolla,et al.  Hyperhomocysteinemic Alzheimer's mouse model of amyloidosis shows increased brain amyloid β peptide levels , 2006, Neurobiology of Disease.

[49]  S. Sultana,et al.  Tamarix gallica ameliorates thioacetamide–induced hepatic oxidative stress and hyperproliferative response in Wistar rats , 2006, Journal of enzyme inhibition and medicinal chemistry.

[50]  Ehud Gazit,et al.  Inhibition of Amyloid Fibril Formation by Polyphenols: Structural Similarity and Aromatic Interactions as a Common Inhibition Mechanism , 2006, Chemical biology & drug design.

[51]  K. Ashe,et al.  Age-Dependent Neurofibrillary Tangle Formation, Neuron Loss, and Memory Impairment in a Mouse Model of Human Tauopathy (P301L) , 2005, The Journal of Neuroscience.

[52]  F. D’Anselmi,et al.  S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production , 2005, Molecular and Cellular Neuroscience.

[53]  N. D. De Santo,et al.  Homocysteine and oxidative stress , 2003, Amino Acids.

[54]  R. Liu,et al.  Inhibition of protein phosphatase 2A- and protein phosphatase 1-induced tau hyperphosphorylation and impairment of spatial memory retention in rats , 2003, Neuroscience.

[55]  G. Perry,et al.  Oxidative Stress Increases Expression and Activity of BACE in NT2 Neurons , 2002, Neurobiology of Disease.

[56]  E. Itarte,et al.  PP1/PP2A phosphatases inhibitors okadaic acid and calyculin A block ERK5 activation by growth factors and oxidative stress , 2002, FEBS letters.

[57]  D. Butterfield,et al.  Lipid peroxidation and protein oxidation in Alzheimer's disease brain: Potential causes and consequences involving amyloid β-peptide-associated free radical oxidative stress , 2002 .

[58]  W. Kisiel,et al.  Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. , 2001, The Journal of clinical investigation.

[59]  D. Campion,et al.  The pathogenic L392V mutation of presenilin 1 decreases the affinity to glycogen synthase kinase-3β , 2000, Neuroscience Letters.

[60]  R Clarke,et al.  Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. , 1998, Archives of neurology.

[61]  K. Imahori,et al.  Characterization of tau phosphorylation in glycogen synthase kinase-3beta and cyclin dependent kinase-5 activator (p23) transfected cells. , 1998, Biochimica et biophysica acta.

[62]  I. Grundke‐Iqbal,et al.  Restoration of biological activity of Alzheimer abnormally phosphorylated tau by dephosphorylation with protein phosphatase-2A, -2B and -1. , 1996, Brain research. Molecular brain research.

[63]  F Benfenati,et al.  Synaptic vesicle phosphoproteins and regulation of synaptic function. , 1993, Science.

[64]  M. Khalid,et al.  Tamarix gallica : For traditional uses , phytochemical and pharmacological potentials , 2016 .

[65]  C. H. T. de Paula da Silva,et al.  Alzheimer's disease: A review from the pathophysiology to diagnosis, new perspectives for pharmacological treatment. , 2016, Current medicinal chemistry.

[66]  Liang Shen,et al.  Associations between Homocysteine, Folic Acid, Vitamin B12 and Alzheimer's Disease: Insights from Meta-Analyses. , 2015, Journal of Alzheimer's disease : JAD.

[67]  Q. Tian,et al.  Novel multipotent AChEI-CCB attenuates hyperhomocysteinemia-induced memory deficits and Neuropathologies in rats. , 2014, Journal of Alzheimer's disease : JAD.

[68]  Swatantra Bahadur Singh,et al.  Phytochemical Screening and Physicochemical Parameters of Crude Drugs : A Brief Review , 2014 .

[69]  Z. A. Oztürk,et al.  Altered levels of homocysteine and serum natural antioxidants links oxidative damage to Alzheimer's disease. , 2013, Journal of Alzheimer's disease : JAD.

[70]  G. Russo,et al.  The flavonoid quercetin in disease prevention and therapy: facts and fancies. , 2012, Biochemical pharmacology.

[71]  M. Sharma,et al.  ANTI- INFLAMMATORY AND ANALGESIC ACTIVITY OF TAMARIX GALLICA , 2012 .

[72]  R. Nitrini,et al.  Peripheral oxidative stress biomarkers in mild cognitive impairment and Alzheimer's disease. , 2011, Journal of Alzheimer's disease : JAD.

[73]  R. von Bernhardi Glial cell dysregulation: a new perspective on Alzheimer disease. , 2007, Neurotoxicity research.

[74]  Peter Johnson,et al.  Homocysteine and its derivatives as possible modulators of neuronal and non-neuronal cell glutamate receptors in Alzheimer's disease. , 2007, Journal of Alzheimer's disease : JAD.

[75]  S. Seshadri Elevated plasma homocysteine levels: risk factor or risk marker for the development of dementia and Alzheimer's disease? , 2006, Journal of Alzheimer's disease : JAD.

[76]  R. Friedland,et al.  Plasma total homocysteine levels, dietary vitamin B6 and folate intake in AD and healthy aging. , 2003, The journal of nutrition, health & aging.