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Nutraceuticals for Cognitive Dysfunction

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Nutraceuticals in Veterinary Medicine

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Abstract

With increasing age, humans and animals suffer from partial or complete loss of cognition and memory. As a result, quality of life declines significantly. Among many underlying mechanisms, a significant decline in the neurotransmitter acetylcholine (ACh), an increase in N-methyl-d-aspartate (NMDA), and oxidative stress are the most recognized events involved in cognition impairment, especially memory and learning. Like chronic neurodegenerative Alzheimer’s disease (AD) in humans, canines and felines suffer from memory loss as they become older. Currently, for AD treatment in humans, an NMDA receptor antagonist memantine in combination with the acetylcholinesterase (AChE) inhibitor donepezil, rivastigmine, or galantamine appears to be the best option. A number of therapeutic drugs (selegiline, gabapentin, buspirone, memantine, etc.) are also available for treatment of canine cognition dysfunction (CCD)/cognitive dysfunction syndrome (CDS). A large number of plant extracts, their ingredients, and bioactive compounds of animal origin have been investigated for anticholinesterase (anti-ChE), antioxidative, anti-inflammatory, and immunomodulatory activities, as well as anti-Aβ aggregation and deposition in the brain. Some of these substances have also been shown to normalize the blood-brain barrier permeability and integrity, while others have been demonstrated to restore mitochondrial function. A small number of plant extracts have also shown MAO-B inhibitory property. Currently, dementic dogs and cats are given nutraceuticals and/or a therapeutic diet to improve their cognition and memory. This chapter describes various nutraceuticals and substances that have potential to improve cognition and memory in senior dogs and cats.

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References

  • Abd El-Wahab AE, Ghareeb DA, Sarhan EEM et al (2013) In vitro biological assessment of Berberis vulgaris and its active constituent, berberine: antioxidant, anti-acetylcholinesterase, anti-diabetic and anticancer effects. BMC Compliment Altern Med 13:218–244

    Google Scholar 

  • Adalier N, Parker H (2016) Vitamin E, turmeric and saffron in treatment of Alzheimer’s disease. Antioxidants 5:40

    PubMed Central  Google Scholar 

  • Ahmed H (2012) Modulatory effects of vitamin E, acetyl-L-carnitine and α-lipoic acid on new potential biomarkers for Alzheimer’s disease in rat model. Exp Toxicol Pathol 64(6):549–556

    CAS  PubMed  Google Scholar 

  • Akhondzadeh S, Shafiee SM, Harirchian MH et al (2010) A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease. Psychopharmacology 207:637–643

    CAS  PubMed  Google Scholar 

  • Asai M, Iwata N, Yoshikawa A et al (2007) Berberine alters the processing of Alzheimer’s amyloid precursor protein to decrease Abeta secretion. Biochem Biophys Res Commun 352(2):498–502

    CAS  PubMed  Google Scholar 

  • Asian Ginseng (2016) National center for complementary and integrative health. US National Institutes of Health, Bethesda

    Google Scholar 

  • Attele AS, Wu JA, Yuan CS (1999) Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 58(11):1685–1693

    CAS  PubMed  Google Scholar 

  • Ay M, Charli A, Jin H et al (2016) Quercetin. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 447–452

    Google Scholar 

  • Ayaz M, Junaid M, Ullah F et al (2015) Comparative chemical profiling, cholinesterase inhibitions and anti-radicals properties of essential oils from Polygonum hydropiper L: a preliminary anti-Alzheimer’s study. Lipids Health Dis 14:141

    PubMed  PubMed Central  Google Scholar 

  • Azkona G, Garcia-Belenguer S, Chacon G et al (2009) Prevalence and risk factors of behavioral changes associated with age-related cognitive impairment in geriatric dogs. J Small Anim Pract 50:87–91

    CAS  PubMed  Google Scholar 

  • Bain MJ, Cliff KD, Ruehl WW (2001) Predicting behavioral changes associated with age-related cognitive impairment in dogs. J Am Vet Med Assoc 218:1792–1795

    CAS  PubMed  Google Scholar 

  • Balducci C, Forloni G (2018) Novel targets in Alzheimer’s disease: a special focus on microglia. Pharmacol Res 130:402–413

    CAS  PubMed  Google Scholar 

  • Baumeister J, Barthel T, Geis KR et al (2008) Influence of phosphatidylserine on cognitive performance and cortical activity after induced stress. Nutr Neurosci 11:103–110

    CAS  PubMed  Google Scholar 

  • Bazinet RP, Layé S (2014) Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci 15:771–785

    CAS  PubMed  Google Scholar 

  • Bharti VK, Malik JK, Gupta RC (2016) Ashwagandha: multiple health effects. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 717–733

    Google Scholar 

  • Bhattacharya SK, Kumar A, Ghosal S (1995) Effects of glycowithanolides from Withania somnifera on an animal model of Alzheimer’s disease and perturbed central cholinergic markers of cognition in rats. Phytother Res 9:110–113

    CAS  Google Scholar 

  • Bhattacharya SK, Satyan KS, Ghosal S (1997) Antioxidant activity of glycowithanolides from Withania somnifera. Indian J Exp Biol 35(3):236–239

    CAS  PubMed  Google Scholar 

  • Bittner DM (2009) Combination therapy of acetylcholinesterase inhibitor and vitamin E in Alzheimer disease. J Clin Psychopharmacol 29:511–513

    PubMed  Google Scholar 

  • Cai Z, Wang C, Yang W (2016) Role of berberine in Alzheimer’s. Neuropsychiatr Dis Treat 12:2509–2520

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cespedes CL, Balbontin C, Avila JG et al (2017) Inhibition on cholinesterase and tyrosinase by alkaloids and phenolics from Aristotelia chilensis leaves. Food Chem Toxicol 109:984–995

    CAS  PubMed  Google Scholar 

  • Chan P, Xia Q, Fu P (2007) Ginkgo biloba leaves extract: biological, medicinal and toxicological effects. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 25:211–244

    CAS  PubMed  Google Scholar 

  • Chandra V, Pandav R, Dodge HH et al (2001) Incidence of Alzheimer’s disease in a rural community in India. The Indo-US study. Neurology 57:985–989

    CAS  PubMed  Google Scholar 

  • Chen WF (2006) Curcumin and its analogues as potent inhibitors of low density lipoprotein oxidation. Free Radic Biol Med 40(3):526–535

    CAS  PubMed  Google Scholar 

  • Chen F, Eckman EA, Eckman CB (2006) Reduction in levels of the Alzheimer’s amyloid beta peptide after oral administration of ginsenosides. FASEB J 20:1269–1271

    CAS  PubMed  Google Scholar 

  • Chen CF, Chiou WF, Zhang JT (2008) Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium. Acta Pharmacol Sin 29:1103–1108

    CAS  PubMed  Google Scholar 

  • Chen D, Liu F, Wan J-B et al (2017) Effect of Royal jelly proteins on spatial memory in aged rats: metabolomics analysis in urine. J Agric Food Chem 65(15):3151–3159

    CAS  PubMed  Google Scholar 

  • Choi KT (2008) Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng C.A. Meyer. Acta Pharmacol Sin 29:1109–1118

    CAS  PubMed  Google Scholar 

  • Choudhary MI, Yousuf S, Nawaz SA et al (2004) Cholinesterase inhibiting withanolides from Withania somnifera. Chem Pharm Bull 52(11):1358–1361

    CAS  Google Scholar 

  • Chun YS, Kim J, Chung S et al (2017) Protective roles of Monsonia angustifolia and its active compounds in experimental models of Alzheimer’s disease. J Agric Food Chem 65:3133–3140

    CAS  PubMed  Google Scholar 

  • Cicero AFG, Fogacci F, Banach M (2018) Botanicals and phytochemicals active on cognitive decline: the clinical evidence. Pharmacol Res 130:204–212

    CAS  PubMed  Google Scholar 

  • Coppock RW, Dziwenka M (2016) Green tea extract. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 633–652

    Google Scholar 

  • Cortes N, Alvarez R, Osorio EH (2015) Alkaloid metabolite profiles by GC/MS and acetylcholinesterase inhibitory activities with binding-mode predictions of five Amaryllidaceae plants. J Pharm Biomed Anal 102:222–228

    CAS  PubMed  Google Scholar 

  • Cotman CW, Head E, Muggenburg BA et al (2002) Brain aging in the canine: a diet enriched in antioxidants reduces cognitive dysfunction. Neurobiol Aging 23(5):809–818

    CAS  PubMed  Google Scholar 

  • Crook TH, Tinklenberg J, Yesavage J et al (1991) Effects of phosphatidylserine in age-associated memory impairment. Neurology 41:644–649

    CAS  PubMed  Google Scholar 

  • D’Amilio M, Puglisi-Allegra S, Mercuri N (2018) The role of dopaminergic midbrain in Alzheimer’s disease: translating basic science into clinical practice. Pharmacol Res 130:414–419

    Google Scholar 

  • Danthiir V, Hosking DE, Nettelbeck T et al (2018) An 18-month randomized, double-blind, placebo-controlled trial of DHA-rich fish oil to prevent age-related cognitive decline in cognitively normal older adults. Am J Clin Nutr 107:754–762

    PubMed  Google Scholar 

  • Das A, Shanker G, Nath C et al (2002) A comparative study in rodents of standardized extracts of Bacopa monnieri and Ginkgo biloba: anticholinesterase and cognitive enhancing activities. Pharmacol Biochem Behav 73:893–900

    CAS  PubMed  Google Scholar 

  • DeFeudis F, Drieu K (2000) Ginkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications. Curr Drug Targets 1:25–58

    CAS  PubMed  Google Scholar 

  • DeSouza JM, Goncalves BDC, Gomez MV et al (2018) Animal toxins as therapeutic tools to treat neurodegenerative diseases. Front Pharmacol 9:145

    Google Scholar 

  • Ding J, Xi YD, Zhang DD et al (2013) Soybean isoflavones ameliorates β-amyloid 1-42-induced learning and memory deficit in rats by protecting synaptic structure and function. Synapse 67(12):856–864

    CAS  PubMed  Google Scholar 

  • Dodd CE, Zicker SC, Jewell DE et al (2003) Can a fortified food affect the behavioral manifestations of age-related cognitive decline in dogs. Vet Med 98:396–408

    Google Scholar 

  • Dohi S, Terasaki M, Makino M (2009) Acetylcholinesterase inhibitory activity and chemical composition of commercial essential oil. J Agric Food Chem 57:4313–4318

    CAS  PubMed  Google Scholar 

  • Drapeau MD, Albert S, Kucharski R et al (2006) Evaluation of the yellow/major royal jelly protein family and the emergence of social behavior in honey bees. Genome Res 16:1385–1394

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dugoua JJ, Mills E, Perri D et al (2006) Safety and efficacy of ginkgo (Ginkgo biloba) during pregnancy and lactation. Can J Clin Pharmacol 13:e277–e284

    PubMed  Google Scholar 

  • Dysken MW, Sano M, Asthana S et al (2014) Effect of vitamin E and memantine on functional decline in Alzheimer disease. The TEAM-AD VA Cooperative Randomized Trial. JAMA 311:33–44

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dziwenka M, Coppock RW (2016) Ginkgo biloba. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 681–691

    Google Scholar 

  • El Idrissi A (2008) Taurine improves learning and retention in aged mice. Neurosci Lett 436:19–22

    PubMed  Google Scholar 

  • Federico A, Cardaioloi E, Da Pozzo P et al (2012) Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci 322:254–262

    CAS  PubMed  Google Scholar 

  • Filho FO, Alcântra DB, Rodrigues THS et al (2018) Development and validation of a reversed phase HPLC method for determination of anacardic acids in cashew (Anacardium occidentale) nut shell liquid. J Chromatogr Sci 56(4):300–306

    CAS  Google Scholar 

  • Galasko D (2006) Biological markers. In: Gauthier S (ed) Clinical diagnosis and management of Alzheimer’s disease, 3rd edn. Informa Healthcare, Boca Raton, pp 125–133

    Google Scholar 

  • Garcia-Alloza M, Borrelli LA, Rozkalne A et al (2007) Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. J Neurochem 102:1095–1104

    CAS  PubMed  Google Scholar 

  • Garvilova SI, Preuss UW, Wong JWM et al (2014) Efficacy and safety of Ginkgo biloba extract EGb 761 in mild cognitive impairment with neuropsychiatric symptoms: a randomized, placebo-controlled, double-blind, multi-center trial. In J Geriatr Psychiatry 29:1087–1095

    Google Scholar 

  • Gasca CA, Castillo WO, Takahashi CS et al (2017) Assessment of anti-cholinesterase activity and cytotoxicity of cagaita (Eugenia dysenterica) leaves. Food Chem Toxicol 109:996–1002

    CAS  PubMed  Google Scholar 

  • Geraldo E, Lloret A, Fuchsberger T et al (2014) Aβ and tau toxicities in Alzheimer’s are linked via oxidative stress-induced P38 activation: protective role of vitamin E. Redox Biol 2:873–877

    Google Scholar 

  • Geromichalos GD, Lamari FN, Papandreou MA et al (2012) Saffron as a source of novel acetylcholinesterase inhibitors: molecular docking and in vitro enzymatic studies. J Agric Food Chem 60:6131–6138

    CAS  PubMed  Google Scholar 

  • Ghadrdoost B, Vafaei AA, Rashidy-Pour A et al (2011) Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats. Eur J Pharmacol 667:222–229

    CAS  PubMed  Google Scholar 

  • Ghaffari SH, Hatami H, Dehghan G (2015) Saffron ethanolic extract attenuates oxidative stress, spatial learning, and memory impairments induced by local injection of ethidium bromide. Res Pharm Sci 10:222–232

    PubMed  PubMed Central  Google Scholar 

  • Ghobeh M, Ahmadian S, Meratan AA et al (2014) Interaction of Aβ25-35 fibrillation products with mitochondria: effects of small molecule natural products. Biopolymers 102(6):473–486

    CAS  PubMed  Google Scholar 

  • Gibson GE, Hirsch JA, Cirio RT et al (2013) Abnormal thiamine-dependent processes in Alzheimer’s disease: lessons from diabetes. Mol Cell Neurosci 55:17–25

    CAS  PubMed  Google Scholar 

  • Go Y-M, Fernandes J, Hu X et al (2018) Mitochondrial network responses in oxidative physiology and disease. Free Radic Biol Med 116:31–40

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gu MY, Kim J, Yang YO (2016) The neuroprotective effects Justicidin A on amyloid beta25-35-induced neuronal cell death through inhibition of tau hyperphosphorylation and induction of autophagy in SH-SY5Y cells. Neurochem Res 41:1458–1467

    CAS  PubMed  Google Scholar 

  • Gupta RC, Dekundy A (2005) memantine does not influence AChE inhibition in rat brain by donepezil or rivastigmine but does with DFP. Drug Develop Res 64:71–81

    CAS  Google Scholar 

  • Gupta RK, Gupta RC (2018) Biomarkers of blood-brain barrier dysfunction. In: Gupta RC (ed) Biomarkers in toxicology, 2nd edn. Academic Press/Elsevier, Amsterdam

    Google Scholar 

  • Gupta RC, Pitt J, Zaja-Milatovic S (2015) Blood-brain barrier damage and dysfunction by chemical toxicity. In: Gupta RC (ed) Handbook of toxicology of chemical warfare agents. Academic Press/Elsevier, Amsterdam, pp 725–739

    Google Scholar 

  • Gurley BJ, Fifer EK, Gardner Z (2012) Pharmacokinetic herb-drug interactions (Part 2): drug interactions involving popular botanical supplements and their clinical relevance. Planta Med 78:1490–1514

    CAS  PubMed  Google Scholar 

  • Hamaguchi T, Ono K, Yamada M (2010) Curcumin and Alzheimer’s disease. CNS Neurosci Ther 16:285–297

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hampel H, Vergallo A, Aguilar LF et al (2018) Precision pharmacology for Alzheimer’s disease. Pharmacol Res 130:331–365

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hansen MV, Danielsen AK, Hageman I et al (2014) The therapeutic or prophylactic effect of exogenous melatonin against depression and depressive symptoms: a systematic review and meta-analysis. Eur Neuropsychopharmacol 24:1719–1728

    CAS  PubMed  Google Scholar 

  • Hartsel JA, Eades J, Hickory B et al (2016) Cannabis sativa and Hemp. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 735–754

    Google Scholar 

  • Head E (2007) Combining an antioxidant-fortified diet with behavioral enrichment leads to cognitive improvement and reduced brain pathology in aging canines: strategies for healthy aging. Ann N Y Acad Sci 1114:398–406

    CAS  PubMed  Google Scholar 

  • Hong SM, Soe KH, Lee TH et al (2017) Cognitive improving effects by highbush blueberry (Vaccinium corymbosum L.) vinegar on Scopolamine-induced amnesia mice model. J Agric Food Chem 66(1):99–107

    PubMed  Google Scholar 

  • Hosmani R (2009) Neuroprotective efficacy of Bacopa Monnieri against rotenone induced oxidative stress and neurotoxicity in Drosophila melanogaster. Neurotoxicology 30:977–985

    Google Scholar 

  • Hussein HM, Abd-Elmegied A, Ghareeb DA et al (2018) Neuroprotective effect of berberine against environmental heavy metals-induced neurotoxicity and Alzheimer’s-like disease in rats. Food Chem Toxicol 111:432–444

    Google Scholar 

  • Hwang S, Lim JW, Kim H (2017) Inhibitory effect of lycopene on amyloid-β-induced apoptosis in neuronal cells. Nutrients 9:883

    PubMed Central  Google Scholar 

  • Ihl R, Bachinskaya N, Korczyn AD et al (2011) Efficacy and safety of a once-daily formulation of Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: a randomized controlled trial. Int J Geriatr Psychiatry 26:1186–1194

    PubMed  Google Scholar 

  • Ikeda-Douglas CJ, Zicker SC, Estrada J et al (2004) Prior experience, antioxidants, and mitochondrial cofactors improve cognitive dysfunction in aged beagles. Vet Ther 5:5–16

    PubMed  Google Scholar 

  • Imai H, Moriyasu K, Nakahata A et al (2017) Soy peptide ingestion augments the synthesis and metabolism of noradrenaline in the mouse brain. Biosci Biotechnol Biochem 81(5):1007–1013

    CAS  PubMed  Google Scholar 

  • Imran M, Ullah F, Ayaz M et al (2017) Anticholinesterase and antioxidant potentials of Nonea micrantha Bioss. And Reut along with GC-MS analysis. BMC Compliment Altern Med 17:499

    Google Scholar 

  • Ingkaninan K, Phengpa P, Yuenyongsawad S et al (2006) Acetylcholinesterase inhibitors from Stephania venosa tuber. J Pharm Pharmacol 58(5):695–700

    CAS  PubMed  Google Scholar 

  • Islam MR, Zaman A, Jahan I et al (2013) In silico QSAR analysis of quercetin reveals its potential as therapeutic drug for Alzheimer’s disease. J Young Pharm 5:173–179

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jamnik P, Goranovič D, Raspor P (2007) Antioxidative action of royal jelly in the yeast cell. Exp Gerontol 42:494–600

    Google Scholar 

  • Jardim FR (2018) Resveratrol and brain mitochondria: a review. Mol Neurobiol 55(3):2085–2101

    CAS  PubMed  Google Scholar 

  • Javeri I, Chand N (2016) Curcumin. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 435–445

    Google Scholar 

  • Jayasena T, Poljak A, Smythe G et al (2013) The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer’s disease. Ageing Res Rev 12:867–883

    CAS  PubMed  Google Scholar 

  • Joffre C, Grégoire S, De Smelt V et al (2016) Modulation of brain PUFA content in different experimental models of mice. Prostaglandins Leukot Essent Fatty Acids 114:1–10

    CAS  PubMed  Google Scholar 

  • Joshi YB, Pratico D (2012) Vitamin E in aging, dementia, and Alzheimer’s disease. Biofactors 38:90–97

    CAS  PubMed  Google Scholar 

  • Kamkaew N, Scholfield CN, Ingkaninan K et al (2011) Bacopa monnieri and its constituents is hypotensive in anesthetized rats and vasodilator in various artery types. J Ethnopharmacol 137:790–795

    PubMed  Google Scholar 

  • Kandel ER (2012) The molecular biology of memory: cAMP, PKA. CRE, CREB-1, CREB-2, and CPEB. Mol Brain 5:14

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kanski J, Aksenova M, Stoyanova A et al (2002) Ferulic acid antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro: structure-activity studies. J Nutr Biochem 13(5):273–281

    CAS  PubMed  Google Scholar 

  • Katayama S, Imai R, Sugiyama H et al (2014) Oral administration of soy peptides suppresses cognitive decline by induction of neurotrophic factors in SAMP8 mice. J Agric Food Chem 62:3563–3569

    CAS  PubMed  Google Scholar 

  • Kennedy DO, Scholey AB, Wesnes KA (2001) Dose dependent changes in cognitive performance and mood following acute administration of ginseng to healthy young volunteers. Nutr Neurosci 4:295–310

    CAS  PubMed  Google Scholar 

  • Khoshpey B, Djazayeri S, Amiri F et al (2016) Effect of royal jelly intake on serum glucose, apolipoprotein A-1 (ApoA-1), apolipoprotein B (ApoB) and ApoB/ApoA-1 ratios in patients with type 2 diabetes: a randomized, double-blind clinical trial study. Can J Diabetes 40:324–328

    PubMed  Google Scholar 

  • Kim Y-S, Woo Y-Y, Han C-K et al (2015) Safety analysis of Panax Ginseng in randomized clinical trials: a systematic review. Medicines 2(2):106–126

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kohno K, Okamoto I, Sano O et al (2004) Royal jelly inhibits the production of proinflammatory cytokines by activated macrophages. Biosci Biotechnol Biochem 68:138–145

    CAS  PubMed  Google Scholar 

  • Kuboyama T, Tohda C, Komatsu K (2006) Withanoside IV and its active metabolite, sominone, attenuate Aβ25-35-induced neurodegeneration. Eur J Neurosci 23(6):1417–1426

    PubMed  Google Scholar 

  • Kulkarni SK, Dhir A (2008) On the mechanism of antidepressant-like action of berberine chloride. Eur J Pharmacol 589(1–3):163–172

    CAS  PubMed  Google Scholar 

  • Kulkarni SK, Dhir A (2010) Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders. Phytother Res 24(3):317–324

    CAS  PubMed  Google Scholar 

  • Kumar A, Chopra EK, Mukherjee M et al (2015) Current knowledge and pharmacological profile of berberine: an update. Eur J Pharmacol 761:288–297

    CAS  PubMed  Google Scholar 

  • Landsberg G (2005) Therapeutic agents for the treatment of cognitive dysfunction syndrome in senior dogs. Progr Neropsychopharmacol Biol Psychiatry 29:471–479

    CAS  Google Scholar 

  • Landsberg GM, Araujo JA (2005) Behavior problems in geriatric pets. Vet Clin North Am Small Anim Pract 35(3):675–698

    PubMed  Google Scholar 

  • Landsberg GM, Hunthausen W, Ackerman L (2003) The effect of aging on the behavior of senior pets. In: Landsberg GM, Hunthausen W, Ackerman W (eds) Handbook of behavior problems of the dog and cat. Saunders, Edinburgh, pp 269–304

    Google Scholar 

  • Landsberg GM, Nichol J, Araujo JA (2012) Cognitive dysfunction syndrome: a disease of canine and feline brain aging. Vet Clin North Am Small Anim Pract 42:749–768

    PubMed  Google Scholar 

  • Layé S, Nadjar A, Joffre C et al (2018) Anti-inflammatory effects of omega-3 fatty acids in the brain: physiological mechanisms and relevance to pharmacology. Pharmacol Rev 70:12–38

    PubMed  Google Scholar 

  • Le XT, Pham HTN, Van Nguyen T et al (2015) Protective effects of Bacopa monnieri on ischemia-induced cognitive deficits in mice: the possible contribution of bacopaside I and underlying mechanism. J Ethnopharmacol 164:37–45

    PubMed  Google Scholar 

  • Lebars PL, Katz MM, Berman N et al (1997) A placebo-controlled, double blinded, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA 278:1327–1332

    CAS  Google Scholar 

  • Lee Y, Jin Y, Lim W et al (2003) A ginsenoside-Rh1, a component of ginseng saponin, activates estrogen receptor in human breast carcinoma MCF-7 cells. J Steroid Biochem Mol Biol 84:463–468

    CAS  PubMed  Google Scholar 

  • Lee HA, Kim JE, Sung JE et al (2018) Asparagus cochinchinensis stimulates release of nerve growth factor and abrogates oxidative stress in the Tg2576 model for Alzheimer’s disease. BMC Compliment Altern Med 18:125

    Google Scholar 

  • Leuner B, Kozorovitskiy Y, Gross CG et al (2007) Diminished adult neurogenesis in the marmoset brain precedes old age. Proc Natl Acad Sci USA 104:17169–17173

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li Q, Zhao HF, Zhang ZF et al (2009) Long-term green tea catechin administration prevents spatial learning and memory impairment in senescence-accelerated mouse prone-8 mice by decreasing a beta (1-42) oligomers and up-regulating synaptic plasticity-related proteins in the hippocampus. Neuroscience 163:741–749

    CAS  PubMed  Google Scholar 

  • Li NJ, Zhou L, Li W et al (2015) Protective effects of ginsenosides Rg1 and Rb1 on an Alzheimer’s disease mouse model: a metabolomic study. J Chromatogr B Anal Technol Biomed Life Sci 985:54–61

    CAS  Google Scholar 

  • Li Y, Chen T, Miao X et al (2017) Zebrafish: a promising in vivo model for assessing the delivery of natural products, fluorescence dyes and drugs across the blood-brain barrier. Pharmacol Res 125:246–257

    CAS  PubMed  Google Scholar 

  • Li H, Wang P, Huang F et al (2018) Astragaloside IV protects blood-brain barrier integrity from LPS-induced disruption via activating Nrf2 antioxidant signaling pathway in mice. Toxicol Appl Pharmacol 340:58–66

    CAS  PubMed  Google Scholar 

  • Lim GP, Chu T, Yang F et al (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 21:8370–8477

    CAS  PubMed  PubMed Central  Google Scholar 

  • Limpeanchob N, Jaipan S, Rattanakaruna S et al (2008) Neuroprotective effect of Bacopa monnieri on beta-amyloid-induced cell death in primary cortical culture. J Ethnopharmacol 120:112–117

    PubMed  Google Scholar 

  • Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795

    CAS  PubMed  Google Scholar 

  • Lin N, Chen S, Zhang H et al (2018) Quantification of major royal jelly protein 1 in fresh royal jelly by ultraperformance liquid chromatography-Tandem mass spectrometry. J Agric Food Chem 66:1270–1278

    CAS  PubMed  Google Scholar 

  • Liu L, Hoang-Gia T, Wu H et al (2011) Ginsenoside Rb1 improves spatial learning and memory by regulation of cell genesis in the hippocampal subregions of rats. Brain Res 1382:147–154

    CAS  PubMed  Google Scholar 

  • Ma W, Ding B, Yu H et al (2015) Genistein alleviates β-amyloid-induced inflammatory damage through regulating toll-like receptor 4/nuclear factor κB. J Med Food 18(3):273–279

    CAS  PubMed  PubMed Central  Google Scholar 

  • Machado LP, Caralho LR, Young MCM et al (2015) Evaluation of acetylcholinesterase inhibitory activity of Brazilian red macroalgae organic extract. Rev Bras Farmacogn 25:657–662

    CAS  Google Scholar 

  • Madaria A, Farbakova J, Katina S et al (2015) Assessment of severity and progression of canine cognitive dysfunction using the Canine Dementia Scale (CADES). Appl Anim Behav Sci 171:138–145

    Google Scholar 

  • Maebuchi M, Kishi Y, Koikeda T et al (2013) Soy peptide dietary supplementation increases serum dopamine level and improves cognitive dysfunction in subjects with mild cognitive impairment. Jpn Pharmacol Ther 41:67–73

    CAS  Google Scholar 

  • Maheshwari RK, Singh AK, Gaddipati J et al (2006) Multiple biological activities of curcumin: a short review. Life Sci 78:2081–2087

    CAS  PubMed  Google Scholar 

  • Marambaud P, Zhao H, Davies P (2005) Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides. J Biol Chem 280:37377–37382

    CAS  PubMed  Google Scholar 

  • Marcelli S, Ficulle E, Oiccolo L et al (2018) An overview of the possible therapeutic role of SUMOylation in the treatment of Alzheimer’s disease. Pharmacol Res 130:420–437

    CAS  PubMed  Google Scholar 

  • Matsui T, Yukiyoshi A, Doi S et al (2002) Gastrointestinal enzyme production of bioactive peptides from royal jelly protein and their antihypertensive ability in SHR. J Nutr Biochem 13:80–86

    CAS  PubMed  Google Scholar 

  • Maurer I, Zierz S, Möller HJ (2000) A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients. Neurobiol Aging 21:455–462

    CAS  PubMed  Google Scholar 

  • Mazzio E, Deiab S, Park K et al (2013) High throughput screening to identify natural human monoamine oxidase B inhibitors. Phytother Res 27(6):818–828

    CAS  PubMed  Google Scholar 

  • Melov S, Adlard PA, Morten K et al (2007) Mitochondrial oxidative stress causes hyperphosphorylation of tau. PLoS One 2:536

    Google Scholar 

  • Meyer JN, Hartman JH, Mello DF (2018) Mitochondrial toxicity. Toxicol Sci 162(1):15–23

    CAS  PubMed  PubMed Central  Google Scholar 

  • Milgram NW, Head E, Zicker SC et al (2005) Learning ability in aged beagle dogs is preserved by behavioral enrichment and dietary fortification: a two-year longitudinal study. Neurobiol Aging 26(1):77–90

    CAS  PubMed  Google Scholar 

  • Milgram NW, Landsberg G, Merrick D et al (2015) A novel mechanism for cognitive enhancement in aged dogs with the use of a calcium-buffering protein. J Vet Behav Clin Appl Res 10(3):217–222

    Google Scholar 

  • Mishima K, Tozawa T, Satoh K et al (1999) Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer’s type with disturbed sleep-waking. Biol Psychiatry 45(4):417–421

    CAS  PubMed  Google Scholar 

  • Moffat KS, Landsberg GM (2003) An investigation of the prevalence of clinical signs of cognitive dysfunction syndrome (CDS) in cats. JAAHA 39(5):512

    Google Scholar 

  • Mohanta T, Tamboli Y, Zubaidha P (2014) Phytochemical and medicinal importance of Ginkgo biloba L. Nat Prod Res 28:746–752

    CAS  PubMed  Google Scholar 

  • Momtaz S, Hassani S, Khan F et al (2018) Cinnamon, a promising prospect towards Alzheimer’s disease. Pharmacol Res 130:241–258

    CAS  PubMed  Google Scholar 

  • Morán M, Moreno-Lastres D, Marín-Buera L et al (2012) Mitochondrial respiratory chain dysfunction: implications in neurodegeneration. Free Radic Biol Med 53:595–609

    PubMed  Google Scholar 

  • Moran DL, Marone PA, Bauter MR et al (2013) Safety assessment of apoaequorin, a protein preparation: subchronic toxicity study in rats. Food Chem Toxicol 57:1–10

    CAS  PubMed  Google Scholar 

  • Moran DL, Tetteh AO, Goodman RE et al (2014) Safety assessment of the calcium-binding protein, apoaequorin, expressed by Escherichia coli. Regul Toxicol Pharmacol 69(2):243–249

    CAS  PubMed  Google Scholar 

  • Morgan A, Stevens J (2010) Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. J Altern Complement Med 16:753–759

    PubMed  Google Scholar 

  • Morgese MG, Schiavone S, Mhillaj E et al (2018) N-3 PUFA diet enrichment prevents amyloid beta-induced depressive-like phenotype. Pharmacol Res 129:526–534

    CAS  PubMed  Google Scholar 

  • Mori T, Koyama N, Guillot-Sestier MV et al (2013) Ferulic acid is a nutraceutical β-secretase modulator that improves behavioral impairment and Alzheimer-like pathology in transgenic mice. PLoS One 8(2):e55774

    CAS  PubMed  PubMed Central  Google Scholar 

  • Morris MC, Evans DA, Tangney CC et al (2005) Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutr 81:508–514

    CAS  PubMed  Google Scholar 

  • Morris MC, Schneider JA, Li H et al (2015) Tocopherols relation to Alzheimer disease neuropathology in humans. Alzheimers Dement 11:32–39

    PubMed  Google Scholar 

  • Mureşan CI, Schierhorn A, Buttstedt A (2018) The fate of major royal jelly proteins during proteolytic digestion in the human gastrointestinal tract. J Food Agric Chem 66:4164–4170

    Google Scholar 

  • Nagahara AH, Merrill DA, Coppola G et al (2009) Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models for Alzheimer’s disease. Nat Med 15:331–337

    CAS  PubMed  PubMed Central  Google Scholar 

  • Neilsen JC, Hart BL, Cliff KD et al (2001) Prevalence of behavioral changes associated with age-related cognitive impairment in dogs. J Am Vet Med Assoc 218:1787–1791

    Google Scholar 

  • Nunomura A, Castellani RJ, Zhu X et al (2006) Involvement of oxidative stress in Alzheimer disease. J Neuropathol Exp Neurol 65:631–641

    CAS  PubMed  Google Scholar 

  • Obayashi K, Saeki K, Iwamoto J et al (2015) Physiological levels of melatonin relate to cognitive function and depressive symptoms: the HEIJO-KYO cohort. J Clin Endocrinol Metab 100(8):3090–3096

    CAS  PubMed  Google Scholar 

  • Okuda M, Fijita Y, Katsube T et al (2018) Highly water pressurized brown rice improves cognitive dysfunction in senescence-accelerated mouse prone 8 and reduces amyloid beta in the brain. BMC Compliment Altern Med 18:110

    Google Scholar 

  • Olajide OJ, Yawson EO, Gbadamosi IT et al (2017) Ascorbic acid ameliorates behavioral deficits and neuropathological alterations in rat model of Alzheimer’s disease. Environ Toxicol Pharmacol 50:200–211

    CAS  PubMed  Google Scholar 

  • Ono K, Hirohata M, Yamada M et al (2005) Ferulic acid destabilizes preformed β-amyloid fibrils in vitro. Biochem Biophys Res Commun 336:444–449

    CAS  PubMed  Google Scholar 

  • Opii WO, Joshi G, Head E et al (2008) Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: relevance to Alzheimer’s disease. Neurobiol Aging 29(1):51–70

    CAS  PubMed  Google Scholar 

  • Orhan I, Şenol FS, Gülpinar AR et al (2009) Acetylcholinesterase inhibitory and antioxidant properties of Cyclotrichium niveum, Thymus praecox subsp, caucasicus var. caucasicus, Echinacea purpurea and E. pallida. Food Chem Toxicol 47:1304–1310

    CAS  PubMed  Google Scholar 

  • Orhan IE, Senol FS, Shekfeh S et al (2017) Pteryxin-A promising butyrylcholinesterase-inhibiting coumarin derivative from Muttelina purpurea. Food Chem Toxicol 109:970–974

    CAS  PubMed  Google Scholar 

  • Orlando JM (2018) Behavioral nutraceuticals and diets. Vet Clin North Am Small Anim Pract 48(3):473

    PubMed  Google Scholar 

  • Orr SK, Trépanier MO, Bazinet RP (2013) n-3 Polyunsaturated fatty acids in animal models with neuroinflammation. Prostaglandins Leukot Essent Fatty Acids 88:97–103

    CAS  PubMed  Google Scholar 

  • Osella MC, Re G, Odore R et al (2007) Canine cognitive dysfunction syndrome: prevalence, clinical signs and treatment with a neuroprotective nutraceutical. Appl Anim Behav Sci 105:297–310

    Google Scholar 

  • Pan Y (2011) Enhancing brain function in senior dogs: a new nutritional approach. Top Companion Anim Med 26(1):10–16

    PubMed  Google Scholar 

  • Pan Y, Larson B, Araujo JA et al (2010) Dietary supplementation with medium-chain TAG has long-lasting cognition-enhancing effects in aged dogs. Br J Nutr 103:1746–1754

    CAS  PubMed  Google Scholar 

  • Papandreou MA, Kanakis CD, Polissiou MG et al (2006) Inhibitory activity on amyloid-β-aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J Agric Food Chem 54:8762–8768

    CAS  PubMed  Google Scholar 

  • Pedata F, Giovannelli L, Spignoli G et al (1985) Phosphatidylserine increases acetylcholine release from cortical slices in aged rats. Neurobiol Aging 6:337–339

    CAS  PubMed  Google Scholar 

  • Peng WH, Wu CR, Chen CS et al (2004) Anxiolytic effect of berberine on exploratory activity of the mouse in two experimental anxiety models, interaction with drugs acting at 5-HT receptors. Life Sci 75:2451–2462

    CAS  PubMed  Google Scholar 

  • Peng WH, Lo KL, Lee YH et al (2007) Berberine produces anti-depressant-like effects in the forced swim test and in the tail suspension test in mice. Life Sci 81(11):933–938

    CAS  PubMed  Google Scholar 

  • Peng XR, Wang X, Dong JR et al (2017) Rare hybrid dimers with anti-acetylcholinesterase activities from a Safflower (Carthamus tinctorius L.) seed oil cake. J Agric Food Chem 65(43):9453–9459

    CAS  PubMed  Google Scholar 

  • Peng M, Yi YX, Zhang T et al (2018) Stereoisomers of saponins in Panax notoginseng (Sanqi): a review. Front Pharmacol 9:188

    PubMed  PubMed Central  Google Scholar 

  • Perry NSL, Houghton P, Theobald A et al (2000) In vitro inhibition of human erythrocyte acetylcholinesterase by Sativa lavandulaefolia essential oil and constituent terpenes. J Pharm Pharmacol 52:895–902

    CAS  PubMed  Google Scholar 

  • Perry NSL, Bollen C, Perry EK et al (2003) Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav 75:651–659

    CAS  PubMed  Google Scholar 

  • Phachonpai W, Wattanathorn J, Muchimapura S et al (2010) Neuroprotective effect of quercetin encapsulated liposomes: a novel therapeutic strategy against Alzheimer’s disease. Am J Appl Sci 7(4):480–485

    CAS  Google Scholar 

  • Pitt J, Leung Y (2016) Cognitive effects of nutraceuticals. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 29–48

    Google Scholar 

  • Pitt J, Leung Y (2018) Biomarkers of Alzheimer’s disease. In: Gupta RC (ed) Biomarkers in toxicology. Academic Press/Elsevier, Amsterdam. In press

    Google Scholar 

  • Piyabhan P, Wannasiri S, Naowaboot J (2016) Bacopa Monnieri (Brahmi) improved novel object recognition task and increased cerebral vesicular glutamate transporter type 3 in sub-chronic phencyclidine rat model of schizophrenia. Clin Exp Pharmacol Physiol 43(12):1234–1242

    CAS  PubMed  Google Scholar 

  • Pletsch EA, Hamaker BR (2018) Brown rice compared to white rice slows gastric emptying in humans. Eur J Clin Nutr 72(3):367–373

    CAS  PubMed  Google Scholar 

  • Porquet D, Griñán-FerréC FI et al (2014) Neuroprotcive role of trans-resveratrol in murine model of familial Alzheimer’s disease. J Alzheimers Dis 42:1209–1220

    CAS  PubMed  Google Scholar 

  • Pyrzanowska J, Piechal A, Blecharz-Klin K et al (2014) Long-term administration of Greek royal jelly improves spatial memory and influences the concentration of brain neurotransmitters in naturally aged Wistar male rats. J Ethnopharmacol 155:343–351

    CAS  PubMed  Google Scholar 

  • Qin L, Wu X, Block ML et al (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55:453–462

    PubMed  PubMed Central  Google Scholar 

  • Qin L, Liu Y, Hong JS et al (2013) NADPH oxidase and aging drive microglial activation, oxidative stress, and dopaminergic neurodegeneration following systemic LPS administration. Glia 61:855–868

    PubMed  PubMed Central  Google Scholar 

  • Ramirez-Rodriguez G, Ortiz-Lopez L, Dominguez-Alonso A et al (2012) Chronic treatment with melatonin stimulates dendritic maturation and complexity in adult hippocampal neurogenesis of mice. J Pineal Res 50:29–37

    Google Scholar 

  • Ranjan KE, Singh HK, Parkavi A et al (2011) Attenuation of 1-(m-chlorophenyl)-biguanide induced hippocampus-dependent memory impairment by a standardized extract of Bacopa monnieri (BESEB CDRI-08). Neurochem Res 36:2136–2144

    Google Scholar 

  • Reddy PH, Beal MF (2008) Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer’s disease. Trends Mol Med 14:45–53

    CAS  PubMed  PubMed Central  Google Scholar 

  • Reichling J, Frater-Schröder M, Herzog K et al (2006) Reduction of behavioral disturbances in elderly dogs supplemented with a standardized Ginkgo leaf extract. Schweiz Arch Tierheilkd 148(5):257–263

    CAS  PubMed  Google Scholar 

  • Reza ASM, Hossain MS, Akhter S et al (2018) In vitro antioxidant and cholinesterase inhibitory activities of Elatostemma papillosum leaves and correlation with their phytochemical profiles: a study relevant to the treatment of Alzheimer’s disease. BMC Complement Altern Med 18:123

    Google Scholar 

  • Risuleo G (2016) Resveratrol: multiple activities on the biological functionality of the cell. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 453–464

    Google Scholar 

  • Rofina JE, Van Ederen AM, Toussaint MJM et al (2006) Cognitive disturbances in old dogs suffering from the canine counterpart of Alzheimer’s disease. Brain Res 1069:216–226

    CAS  PubMed  Google Scholar 

  • Rong H, Liang Y, Niu Y (2018) Rosmarinic acid attenuates β-amyloid-induced oxidative stress via Akt/GSK-3β/Fyn-mediated Nrf2 activation in PC2 cells. Free Radic Biol Med 120:114–123

    CAS  PubMed  Google Scholar 

  • Rosello A, Warnes G, Meier UC (2012) Cell death pathways and autophagy in the central nervous system and its involvement in neurodegeneration, immunity and central nervous system infection: to die or not to die-that is the question. Clin Exp Immunol 168:52–57

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sabogal-Guaqueta AM, Carrillo-Hormaza L, Osorio E et al (2015) Effects of bioflavonoids from Garcinia madruno on a triple transgenic mouse model of Alzheimer’s disease. Pharmacol Res 129:128–138

    Google Scholar 

  • Sabogal-Guaqueta AM, Munoz-Manco JI, Ramirez-Pineda JR et al (2018) The flavonoid quercetin ameliorates Alzheimer’s disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer’s disease model mice. Neuropharmacology 93C:134–145

    Google Scholar 

  • Sadhukhan P, Saha S, Dutta S et al (2018) Nutraceuticals: an emerging therapeutic approach against the pathogenesis of Alzheimer’s disease. Pharmacol Res 129:100–114

    CAS  PubMed  Google Scholar 

  • Saini N, Singh D, Sandhir R (2012) Neuroprotective effects of Bacopa monnieri in experimental model of dementia. Neurochem Res 37:1928–1937

    CAS  PubMed  Google Scholar 

  • Salvin HE, McGreevy PD, Sachdev PS et al (2010) Under diagnosis of canine cognitive dysfunction: a cross-sectional survey of older companion dogs. Vet J 184(3):277–281

    PubMed  Google Scholar 

  • Salvin HE, McGreevy PD, Sachdev PS et al (2011) The canine cognitive dysfunction rating scale (CCDR): a data-driven and ecologically relevant assessment tool. Vet J 188:331–336

    PubMed  Google Scholar 

  • Schliebs R, Liebmann A, Bhattacharya SK et al (1997) Systemic administration of defined extracts from Withania somnifera (Indian ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain. Neurochem Int 30(2):181–190

    CAS  PubMed  Google Scholar 

  • Schmidt F, Boltze J, Jager C et al (2015) Detection and quantification of β-amyloid, pyroglutamil Aβ, and tau in aged canines. J Neuropathol Exp Neurol 74(9):912–923

    CAS  PubMed  Google Scholar 

  • Scholey AB, Kennedy DO (2002) Acute, dose-dependent cognitive effects of Ginkgo biloba, Panax ginseng and their combination in healthy young volunteers: differential interactions with cognitive demand. Hum Psychopharmacol 17:35–44

    PubMed  Google Scholar 

  • Schon EA, Area-Gomez E (2013) Mitochondria-associated ER membranes in Alzheimer’s disease. Mol Cell Neurosci 55:26–36

    CAS  PubMed  Google Scholar 

  • Schütt T, Toft N, Berendt M (2015) Cognitive function, progression of age-related behavioral changes, biomarkers, and survival in dogs more than 8 years old. J Vet Intern Med 29(6):1569–1577

    PubMed  PubMed Central  Google Scholar 

  • Sechi S, Chiavolelli F, Spissu N et al (2015) An antioxidant dietary supplement improves brain-derived neurotrophic factor levels in serum of aged dogs: preliminary results. J Vet Med 2015:412501. https://doi.org/10.1155/2015/412501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seibert L (2017) Management of dogs and cats with cognitive dysfunction. Today’s. Vet Pract 7(5):1–8

    Google Scholar 

  • Sen A, Hongpaisan J (2018) Hippocampal microvasculature changes in association with oxidative stress in Alzheimer’s disease. Free Radic Biol Med 120:192–203

    CAS  PubMed  Google Scholar 

  • Seo EJ, Fischer N, Efferth T (2018) Phytochemicals as inhibitors of NF-kappa B for treatment of Alzheimer’s disease. Pharmacol Res 129:262–273

    CAS  PubMed  Google Scholar 

  • Serrano MAR, Pivatto M, Francisco W et al (2010) Acetylcholinesterase inhibitory pyridine alkaloids of the leaves of Senna multijuga. J Nat Prod 73:482–484

    CAS  PubMed  Google Scholar 

  • Sharman EH, Bondy SC (2016) Melatonin: a safe nutraceutical and clinical agent. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 501–509

    Google Scholar 

  • Shoshan-Barmatz V, Nahon-Crystal E, Shteinfer-Kuzmine A, Gupta R (2018) VDAC1, mitochondrial dysfunction, and Alzheimer’s disease. Pharmacol Res 131:87–101

    CAS  PubMed  Google Scholar 

  • Sigurdsson S, Gudbjarnason S (2007) Inhibition of acetylcholinesterase by extracts and constituents from Angelica archangelica and Geranium sylvaticum. Z Naturforsch C 62(9–10):689–693

    CAS  PubMed  Google Scholar 

  • Skoumalova A, Rofina J, Schwippelova Z et al (2003) The role of free radicals in canine counterpart of senile dementia of the Alzheimer type. Exp Gerontol 38(6):711–719

    CAS  PubMed  Google Scholar 

  • Smith CC, McMahon LL (2005) Estrogen-induced increase in the magnitude of long-term potentiation occurs only when the ratio of NMDA transmission to AMPA transmission is increased. J Neurosci 25:7780–7791

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sorrenti V, Contarini G, Sut S et al (2018) Curcumin prevents acute neuroinflammation and long-term memory impairment induced by systemic lipopolysaccharide in mice. Front Pharmacol 9:183

    PubMed  PubMed Central  Google Scholar 

  • Stough C, Lloyd J, Clarke J et al (2001) The chronic effects of an extract of Bacopa monnieri (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berlin) 156:481–484

    CAS  Google Scholar 

  • Sultana A, Nurun Nabi AHM, Nasir UM et al (2008) A dipeptide YY derived from royal jelly proteins inhibits renin activity. Int J Mol Med 21:677–681

    CAS  PubMed  Google Scholar 

  • Šver L, Oršolić N, Tadić Z et al (1996) A royal jelly as a new potential immunomodulator in rats and mice. Comp Immunol Microbiol Infect Dis 19:31–38

    PubMed  Google Scholar 

  • Taguchi R, Hatayama K, Takahashi T et al (2017) Structure-activity relations of rosmarinic acid derivatives for the amyloid β aggregation inhibition and antioxidant properties. Eur J Med Chem 138:1066–1075

    CAS  PubMed  Google Scholar 

  • Taha AY, Henderson ST, Burnham MW (2009) Dietary enrichment with medium chain triglycerides (AC-1203) elevates polyunsaturated fatty acids in the parietal cortex of aged dogs: implications for treating age-related cognitive decline. Neurochem Res 34(9):1619–1625

    CAS  PubMed  Google Scholar 

  • Tan X-S, Ma J-Y, Feng R et al (2013) Tissue distribution of berberine and its metabolites after oral administration in rats. PLoS One 8(10):e77969

    CAS  PubMed  PubMed Central  Google Scholar 

  • Teodoro JS, Duarte FV, Rolo AP, Palmeira CM (2016) Mitochondria as a target for safety and toxicity evaluation of nutraceuticals. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 387–400

    Google Scholar 

  • Terry AV, Buccafusco JJ (2006) The cholinergic hypothesis of age and Alzheimer’s disease related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther 306:821–827

    Google Scholar 

  • Tokunaga K, Yoshida C, Suzuki K et al (2004) Antihypertensive effect of peptide from royal jelly in spontaneously hypertensive rats. Biol Pharm Bull 27:189–192

    CAS  PubMed  Google Scholar 

  • Trevisan MTS, Macedo FW, Meent M et al (2003) Screening for acetylcholinesterase inhibitors from plants to treat Alzheimer’s disease. Quím Nova 26(3):301–304

    Google Scholar 

  • Uddin MJ, Abdullah-Al-Mamun M, Biswas K et al (2016) Assessment of anticholinesterase activities and antioxidant potentials of Anisomeles indica relevant to the treatment of Alzheimer’s disease. Orient Pharm Exp Med 16:113–121

    CAS  Google Scholar 

  • Uddin MJ, Ali Reza ASM, Abdullah-Al-Mamun M et al (2018) Antinociceptive and anxiolytic and sedative effects of methanol extract of Anisomeles indica: an experimental assessment in mice and computer aided models. Front Pharmacol 9:246

    PubMed  PubMed Central  Google Scholar 

  • Ude C, Schubert-Zsilavecz M, Wurglics M (2013) Ginkgo biloba extracts: a review of the pharmacokinetics of the active ingredients. Clin Pharmacokinet 52:727–749

    CAS  PubMed  Google Scholar 

  • Vedin I, Cederholm T, Freund Levi Y et al (2008) Effects of docosahexaenoic acid-rich n-3 fatty acid supplementation on cytokine release from blood mononuclear leukocytes: the Omega AD study. Am J Clin Nutr 87:1616–1622

    CAS  PubMed  Google Scholar 

  • Velaga MK, Basuri CKR, Taylor KS et al (2014) Ameliorative effects of Bacopa monnieri on lead-induced oxidative stress in different regions of rat brain. Drug Chem Toxicol 37:357–364

    CAS  PubMed  Google Scholar 

  • Vite CH, Head E (2014) Aging in the canine and feline brain. Vet Clin North Am Small Anim Pract 44:1113–1129

    PubMed  PubMed Central  Google Scholar 

  • Wang F, Zhao G, Cheng L et al (2004) Effects of berberine on potassium currents in acutely isolated CA1 pyramidal neurons of rat hippocampus. Brain Res 999:91–97

    CAS  PubMed  Google Scholar 

  • Wang X, Wang R, Xing D et al (2005) Kinetic difference of berberine between hippocampus and plasma in rat after intravenous administration of Coptidis rhizoma extract. Life Sci 77(24):3058–3067

    CAS  PubMed  Google Scholar 

  • Wang X, Su B, Zheng L et al (2009) The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer’s disease. J Neurochem 109:153–159

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang M, Zhao J, Avula B et al (2014) High-resolution gas chromatography/mass spectrometry method for characterization and quantitative analysis of ginkgolic acids in Ginkgo biloba plants, extracts, and dietary supplements. J Agric Food Chem 62:12103–12111

    CAS  PubMed  Google Scholar 

  • Wee JJ, Mee PK, Chung AS (2011) Biological activities of ginseng and its application to human health. In: Benzie IFF, Wachtel-Galor S (eds) Herbal medicine: biomolecular and clinical aspects. CRC Press, Boca Raton

    Google Scholar 

  • Wevers A (2011) Localization of pre- and postsynaptic cholinergic markers in the human brain. Behav Brain Res 221:341–355

    CAS  PubMed  Google Scholar 

  • Wu YH, Feenstra MG, Zhou JN et al (2003) Molecular changes underlying reduced pineal melatonin levels in Alzheimer’s disease: alterations in preclinical and clinical stages. J Clin Endocrinol Metab 88(12):5898–5906

    CAS  PubMed  Google Scholar 

  • Wu D, Wang X, Sun H (2018) The role of mitochondria in cellular toxicity as a potential drug target. Cell Biol Toxicol 34:87–91

    CAS  PubMed  Google Scholar 

  • Xiang C-P, Han J-X, Li X-C et al (2017) Chemical composition and acetylcholinesterase inhibitory activity of essential oils from Piper species. J Agric Food Chem 65:3702–3710

    CAS  PubMed  Google Scholar 

  • Xiao Q, Wang C, Li J et al (2010) Ginkgolide B protects hippocampal neurons from apoptosis induced by beta-amyloid 25-35 partly via up-regulation of brain derived neurotrophic factor. Eur J Pharmacol 647:48–54

    CAS  PubMed  Google Scholar 

  • Xing YZ, Shang HC, Gao XM et al (2008) A comparison of the ancient use of ginseng in traditional Chinese medicine with modern pharmacological experiments and clinical trials. Phytother Res 22:851–858

    Google Scholar 

  • Yan JJ, Cho JY, Kim HS et al (2001) Protection against beta-amyloid peptide toxicity in vivo with long-term administration of ferulic acid. Br J Pharmacol 133(1):89–96

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yan X, Tang J, dos Santos Passos C et al (2015) Characterization of lignanamides from hemp (Cannabis sativa L.) seed and their antioxidant and acetylcholinesterase inhibitory activities. J Agric Food Chem 63:10611–10619

    CAS  PubMed  Google Scholar 

  • Yang MS, Wu MY (2016) Chinese ginseng. In: Gupta RC (ed) Nutraceuticals: efficacy, safety and toxicity. Academic Press/Elsevier, Amsterdam, pp 693–705

    Google Scholar 

  • Yatin SM, Varadarajan S, Butterfield DA (2000) Vitamin E prevents Alzheimer’s amyloid β-peptide (1-42)-induced neuronal protein oxidation and reactive oxygen species production. J Alzheimers Dis 2:123–131

    CAS  PubMed  Google Scholar 

  • Ye M, Fu S, Pi R et al (2009) Neuropharmacological and pharmacokinetic properties of berberine: a review of recent research. J Pharm Pharmacol 61:831–837

    CAS  PubMed  Google Scholar 

  • Yoo KY, Hwang IK, Lim BO et al (2006) Berberry extract reduces neuronal damage and N-methyl-D-aspartate receptor 1 immunoreactivity in the gerbil hippocampus after transient forebrain ischemia. Biol Pharm Bull 29:623–628

    CAS  PubMed  Google Scholar 

  • Yoshida M, Hayashi K, Watadani R et al (2017) Royal jelly improves hyperglycemia in obese/diabetic KK-Ay mice. J Vet Med Sci 79(2):299–307

    CAS  PubMed  Google Scholar 

  • Yu H, Wang D, Zou L et al (2018) Proteomic alterations of brain subcellular organelles caused by low-dose copper exposure: implication for Alzheimer’s disease. Arch Toxicol 92:1363–1382

    CAS  PubMed  Google Scholar 

  • Zamani Z, Reisi P, Alaei H et al (2012) Effect of royal jelly on special learning and memory in rat model of streptozotocin-induced sporadic Alzheimer’s disease. Adv Biomed Res 1:26

    PubMed  PubMed Central  Google Scholar 

  • Zhang J, Yang JQ, He BC et al (2009) Berberine and total base from rhizoma Coptis chinensis attenuate brain injury in an aluminum-induced rat model of neurodegenerative disease. Saudi Med J 30(6):760–766

    PubMed  Google Scholar 

  • Zhang X, Zhang X, Wang C et al (2013) Neuroprotection of early and short-time applying berberine in the acute phase of cerebral ischemia: up-regulated pAkt, pGSK and pCREB, down-regulated NF-κB expression, ameliorated BBB permeability. Brain Res 1459(6):61–70

    Google Scholar 

  • Zhang XZ, Qian SS, Zhang YJ et al (2016) Salvia miltiorrhiza: a source for anti-Alzheimer’s disease drugs. Pharm Biol 54:18–24

    PubMed  Google Scholar 

  • Zhang ZH, Wen L, Yu QY et al (2017) Long-term dietary supplementation with selenium-enriched yeast improves cognitive impairment, reserves synaptic deficits, and mitigates tau pathology in a triple transgenic mouse model of Alzheimer’s disease. J Agric Food Chem 65:4970–4979

    CAS  PubMed  Google Scholar 

  • Zhao Y, Zhao B (2013) Oxidative stress and the pathogenesis of Alzheimer’s disease. Oxid Med Cell Longev 2013:316523

    Google Scholar 

  • Zhao N, Zhong C, Wang Y et al (2008) Impaired hippocampal neurogenesis is involved in cognitive dysfunction induced by thiamine deficiency at early pre-pathological legion stage. Neurobiol Dis 29(2):176–185

    PubMed  Google Scholar 

  • Zhao HF, Li Q, Zhang ZF et al (2009) Long-term ginsenoside consumption prevents memory loss in aged SAMP8 mice by decreasing oxidative stress and up-regulating the plasticity-related proteins in hippocampus. Brain Res 1256:111–122

    CAS  PubMed  Google Scholar 

  • Zhao B, Ren B, Guo R et al (2017a) Supplementation of lycopene attenuates oxidative stress induced neuroinflammation and cognitive impairment via Nrf2/NF-κB transcriptional pathway. Food Chem Toxicol 109:505–516

    CAS  PubMed  Google Scholar 

  • Zhao T, Su G, Wang S et al (2017b) Neuroprotective effects of acetylcholinesterase inhibitory peptides from anchovy (Coilia mystus) against glutamate-induced toxicity in PC12 cells. J Agric Food Chem 65:11192–11201

    CAS  PubMed  Google Scholar 

  • Zhao B, Liu H, Wang J et al (2018) Lycopene supplementation attenuates oxidative stress, neuroinflammation, and cognitive impairment in aged CD-1 mice. J Agric Food Chem 66:3127–3136

    CAS  PubMed  Google Scholar 

  • Zhu F, Qian C (2006) Berberine chloride can ameliorate the spatial memory impairment and increase the expression of interleukin-1beta and inducible nitric oxide synthase in the rat model of Alzheimer’s disease. BMC Neurosci 7:78

    PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Toxicology Department, Breathitt Veterinary Center, Murray State University, Hopkinsville, KY, USA

    Ramesh C. Gupta & Robin B. Doss

  2. Vets Plus Inc., Menomonie, WI, USA

    Ajay Srivastava, Rajiv Lall & Anita Sinha

Authors
  1. Ramesh C. Gupta
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  2. Robin B. Doss
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  3. Ajay Srivastava
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  4. Rajiv Lall
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  5. Anita Sinha
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Correspondence to Ramesh C. Gupta .

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Editors and Affiliations

  1. Department of Toxicology, Breathitt Veterinary Center, Murray State University, Hopkinsville, KY, USA

    Ramesh C. Gupta

  2. Vets Plus Inc., University of Wisconsin–Stout, Menonomie, WI, USA

    Ajay Srivastava

  3. Vets Plus Inc., Menomonie, WI, USA

    Rajiv Lall

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Gupta, R.C., Doss, R.B., Srivastava, A., Lall, R., Sinha, A. (2019). Nutraceuticals for Cognitive Dysfunction. In: Gupta, R., Srivastava, A., Lall, R. (eds) Nutraceuticals in Veterinary Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-04624-8_26

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