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Sunday, 16 March 2014
Alzheimer's disease in Foods, Herbs and Vitamins Points of View
By Kyle J. Norton
Alzheimer's disease is a brain disorder correlated with major reductions of neurons to the respective target areas, named after German physician Alois Alzheimer. Alzheimer's destroys brain cells, causing cognitive modalities severe enough to affect language communication, memory, lifelong hobbies or social life. Alzheimer's gets worse over time, and it is fatal.
According to statistic, over 25 million people in the world today are affected by dementia and most are suffering from Alzheimer's disease. It may be a result of cigarette smoking, midlife high blood pressure and obesity, diabetes, and cerebrovascular lesions and psychosocial factors (eg, high education, active social engagement, physical exercise, and mentally stimulating activity)(1) Strong evidences emerged in epidemiological studies suggested that certain foods(2) may have potential in reduced risk and treatments of Alzheimer's disease.
I. Types of Foods Reduced risk of Alzheimer's disease
1. Cruciferous vegetables
Cruciferous vegetables are the group of vegetables belonging to the family Brassicaceae, including cauliflower, cabbage, cress, bok choy, broccoli etc..
Epidemiological studies has demonstrated reduced risk of Alzheimer's disease in cruciferous consumption. The study of 2148 community-based elderly subjects (aged > or = 65 years) without dementia in New York, after 3.9 years, 253 subjects developed AD during a follow-up. Dietary pattern (DP) analysis of food combination indicated that higher intakes of salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, and dark and green leafy vegetables and a lower intake of high-fat dairy products, red meat, organ meat, and butter are associated to reduced risk of AD.(1)
Tomato is a red, edible fruit, genus Solanum, belonging to family Solanaceae, native to South America. Because of its health benefits, tomato is grown world wide for commercial purpose and often in green house.
Lycopene and alpha carotene found in tometos inhibited symptoms of AD through inhibition of amyloid beta (Aβ) formation, deposition and fibril formation either by reducing the levels of p35 or inhibiting corresponding enzymes(2). In the study of Antioxidants, such as tocopherols and carotenoids, implicated in the prevention of degenerative diseases showed that aging population exhibit a age related decline of levels retinol, total tocopherols, total xanthophylls and total carotenoids(3).
Garlic is a natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties.
S-allyl-L-cysteine (SAC), an active chemical constituents of garlic, showed to inhibit several pathological cascades related to the synaptic degeneration and neuroinflammatory pathways associated with AD. through up and down regulations(4) with intervention to prevent free radicals causes of deterioration of cognitive functions and neurobehavioral activities(5). The Central Food Technological Research Institute supported the binding ability of SAC to Abeta, inducing a partially folded conformation in Abeta.(6) and suggested that consumption of garlic may reduced risk of AD, due to inhibition of Abeta aggregation in human brain(7).
Ginger (Zingiber officinale) or ginger root is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil. It has been used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, colic, etc.
In the Alzheimer disease (AD) rat model, ginger root extract (GRE) administered intra-gastrically to rats after 35 days, exhibited the protective effect against AD through reversed behavioral dysfunction and prevented AD-like symptoms(8). -gingerol, a pungent ingredient of ginger, pretreatment protected against Aβ(25-35)-induced cytotoxicity and apoptotic cell death such as DNA fragmentation, disruption of mitochondrial membrane potential, elevated Bax/Bcl-2 ratio, and activation of caspase-3 via augmentation of antioxidant capacity(9) and inhibition of acetylcholinesterase activities and prevention of lipid peroxidation in the brain(10).
Turmeric is a perennial plant in the genus Curcuma, belonging to the family Zingiberaceae, native to tropical South Asia. The herb has been used in traditional medicine as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc.
Evidences of epidemiological studies suggestion of curcumin in reduced risk of Ad progression. Suggestion of curcumin in treating Alzheimer's disease (AD) depended on the ability to penetrate the blood-brain barrier(11) and on inhibited progression of deposit of beta-amyloid aggregation.(12).
A novel polymeric nanoparticle (PEG-PLGA) encapsulated curcumin, induced adult neurogenesis through activation of the canonical Wnt/β-catenin pathway(secreted signalling proteins released by one cell population will trigger concentration-dependent responses in other cells located some distance away)(13) and brain self-repair mechanis(14). Unfortunately, a 24-week randomized, double blind, placebo-controlled study conducted by the David Geffen School of Medicine at UCLA, oral administration showed no biochemical evidence of efficacy of Curcumin C3 Complex® in AD(15).
Cinnamon is a spice derived from the inner bark of tree, native to South East Asia, of over 300 species of the genus Cinnamomum, belonging to the family Lauraceae.. The herb has been use in herbal and traditional medicine as anti-fungal and bacteria level to improve reproductive organ, prevent flatulence and intestinal cramping, treat indigestion, diarrhea, bad breath, headache, migraine, etc.
Aqueous extract of cinnamon showed to inhibit tau aggregation in vitro and can even induce dissociation of tangles isolated from AD brain and cinnamaldehyde (CA). The organic compound of cinnamon
protected tau from oxidation caused by the reactive oxygen species, H2O2, and prevented subsequent formation of high molecular weight species that are considered to stimulate tangle formation(16) and inhibited tau aggregation associated with Alzheimer's disease in vitro(17). Other study insisted that cinnamon extract (CEppt), markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells and oral administration in AD patients, showed to reduce longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in the brain(18).
7. Black pepper
Black pepper is a is a flowering vine in the genus Pipper, belonging to the family Piperaceae. It has been used in folk medicine in treating constipation, diarrhea, earache, gangrene, heart disease, hernia, hoarseness, indigestion, insect bites, insomnia, joint pain, etc.
Piperine, a main active alkaloid in black pepper exhibited significantly improved memory impairment and neurodegeneration in hippocampus associated with the decrease lipid peroxidation and acetylcholinesterase enzyme(19). In the evaluation the Piperine therapeutic effects in Alzheimer's Disease, at 2 mg/kg dose, reduced the SOD values, immobility and has shown superior results than Donepezil (5 mg/kg), AD drug and increased the acetylcholenesterase values(20).
8. Green Tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
Green tea polyphenols (GTPs) may be a next potential agent in protection of neurodegenerative diseases such as Alzheimer's disease (AD). GTPs have found to inhibit amyloid fibril formation and protect neurons from toxicity induced by β-amyloid and OA-induced neurotoxicity by enhancing the amelioration of learning and memory impairments and also reduction of tau hyperphosphorylation(21). Epigallocatechin gallate polyphenols, isolated from green tea, a selective inhibitor of PKC., combination of EGCG and resveratrol protected against GF 109203X-induced cell death and cytoskeleton degeneration, with a maximal effect at 1 and 3 μM, respectively and cells treated increased PKC gamma (γ) activation and promoted neuronal interconnections(22). (-)-epigallocatechin-3 gallate (EGCG) alone also showed to reduce amyloid-β (Aβ) production in both neuronal and mouse Alzheimer's disease (AD) models(23).
Coffee made from the roasted seeds of the genus Coffee, belonging to the family Rubiaceae native to southern Arabia. Coffee may consist certain substances, effecting the risk of Alzheimers' disease. AD mice given caffeine in their drinking water from young adulthood into older age showed to inhibit memory and cognitive impairment and lower brain levels of amyloid-beta; Abeta)(24)(25). In mice with Alzheimers' disease caused by dysregulated endoplasmic reticulum (ER) calcium (Ca 2+), induced deletion of RyanR3, showed the enhancement of coffee in activation of RyanRs which protected AD neurons from synaptic and network dysfunction(26). Intake of 5 cups of coffee per day(moderate caffeine intake) found to protect against the development of certain cognitive impairment and decreased hippocampal amyloid-beta (Abeta) levels through suppression of both beta-secretase (BACE1), a beta-site amyloid precursor protein cleaving enzyme 1 and presenilin 1 (PS1)/gamma-secretase expression(mutations in the presenilin proteins)(27)(28).
10. Red wine
Red wine made from made dark-coloured (black) grape varieties as a result of anthocyan pigments present in the skin of the grape.
Red wine may be a therapeutic potential for treating AD patients through reduction of forming of beta-amyloid peptid. In human umbilical vein endothelial cells (HUVECs), black grape skin extract inhibited the ROS production, protected the cellular membrane from oxidative damage, and consequently prevented DNA fragmentation(29). Red wine extract resveratrol, in another study inhibited the expression of soluble oligomers of the amyloid-β (Aβ) peptide cause of neurotoxicity, synaptic dysfunction, and memory impairments(30). Polyphenols derived from red wine, according to Mount Sinai School of Medicine, New York, may protect against cognitive deterioration of Alzheimer's disease, thriugh generation and assembly of β-amyloid peptides into neurotoxic oligomeric aggregated species(31).
10. Olive oil
Olive is belongs to the the family Oleaceae, native to the coastal areas of the eastern Mediterranean Basin and south end of the Caspian Sea. Its fruit, is also called the olive and the source of olive oil.
Oleuropein aglycone, the main polyphenol derived from extra virgin olive oil, in the study of the double transgenic TgCRND8 mice, showed to improve the cognitive performance and reduce ß-amyloid levels and plaque deposits, through increase of autophagic markers expression and of lysosomal (break down waste materials and cellular debris)activity(32), induction of the Aβ transgene expression(33) and enhancement of Aβ clearance from the brain(34). The study by VA Medical Center, also found that EVOO inhibited learning and memory deficits found in aging and diseases, due to overproduction of amyloid-β protein, and reversed oxidative damage in the brain(35).
11. Fish oil
Fish oil derived from the tissues of oily fish, contains high amount of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), etc.
Epidemiological studies suggested that higher dietary intake of ω-3 PUFA reduced risk of incident AD and slower cognitive decline(36) through reduction of plasma levels of Aβ42(37) and may be through induced the PTEN expression(ova tumor suppressor gene) by activation of peroxisome proliferator-activated receptor(regulating the expression of genes)(38). Genetically, defection of the ε4 allele of the APOE gene (APOE4), according to the Central Michigan University, in the mu-p75 saporin (SAP)-induced mouse model of AD, daily treatments of Cerise(®) Total-Body-Rhythm™ (TBR; containing tart cherry extract, Nordic fish oil, and refined emu oil), reduced the severity of cognitive deficits in disorders involving cholinergic deficits(39).
Taking altogether, without going into reviews, The list of foods above may be effective in reduced risk and treatment of Alzheimers' disease through improvement of cognitive function, via reduced plasma levels of Aβ42 and ß-amyloid and plaque deposits. Some researchers suggested that larger sample and multi centers studies are necessary to identify the principle ingredients for validation of their effectiveness. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.
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(1) Food combination and Alzheimer disease risk: a protective diet by Gu Y1, Nieves JW, Stern Y, Luchsinger JA, Scarmeas N.( PubMed )
(2) Carotenoids and Alzheimer's disease: an insight into therapeutic role of retinoids in animal models by Obulesu M1, Dowlathabad MR, Bramhachari PV.( PubMed )
(3) Carotenoid, tocopherol, and retinol concentrations in elderly human brain by Craft NE 1, Haitema TB , Garnett KM , Fitch KA , Dorey CK .(PubMed)
(4) The "aged garlic extract:" (AGE) and one of its active ingredients S-allyl-L-cysteine (SAC) as potential preventive and therapeutic agents for Alzheimer's disease (AD) by Ray B1, Chauhan NB, Lahiri DK.( PubMed )
(5) S-allyl cysteine attenuates oxidative stress associated cognitive impairment and neurodegeneration in mouse model of streptozotocin-induced experimental dementia of Alzheimer's type by Javed H1, Khan MM, Khan A, Vaibhav K, Ahmad A, Khuwaja G, Ahmed ME, Raza SS, Ashafaq M, Tabassum R, Siddiqui MS, El-Agnaf OM, Safhi MM, Islam F.( PubMed )
(6) Anti-amyloidogenic activity of S-allyl-L-cysteine and its activity to destabilize Alzheimer's beta-amyloid fibrils in vitro by Gupta VB1, Rao KS.( PubMed )
(7) Garlic extract exhibits antiamyloidogenic activity on amyloid-beta fibrillogenesis: relevance to Alzheimer's disease by Gupta VB1, Indi SS, Rao KS( PubMed )
(8) Protective effects of ginger root extract on Alzheimer disease-induced behavioral dysfunction in rats by Zeng GF1, Zhang ZY, Lu L, Xiao DQ, Zong SH, He JM.( PubMed )
(9) -Gingerol attenuates β-amyloid-induced oxidative cell death via fortifying cellular antioxidant defense system by Lee C1, Park GH, Kim CY, Jang JH.( PubMed )
(10) Inhibition of acetylcholinesterase activities and some pro-oxidant induced lipid peroxidation in rat brain by two varieties of ginger (Zingiber officinale) by Oboh G 1, Ademiluyi AO, Akinyemi AJ .( PubMed )
(11) Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer's disease Tg2576 mice by Cheng KK1, Yeung CF, Ho SW, Chow SF, Chow AH, Baum L.( PubMed )
(12) Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study by Ringman JM1, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, Gylys KH, Badmaev V, Heath DD, Apostolova LG, Porter V, Vanek Z, Marshall GA, Hellemann G, Sugar C, Masterman DL, Montine TJ, Cummings JL, Cole GM.( PubMed )
(13) Curcumin-Loaded Nanoparticles Potently Induce Adult Neurogenesis and Reverse Cognitive Deficits in Alzheimer's Disease Model via Canonical Wnt/β-Catenin Pathway by Tiwari SK1, Agarwal S, Seth B, Yadav A, Nair S, Bhatnagar P, Karmakar M, Kumari M, Chauhan LK, Patel DK, Srivastava V, Singh D, Gupta SK, Tripathi A, Chaturvedi RK, Gupta KC.( PubMed )
(14) Curcumin-Loaded Nanoparticles Potently Induce Adult Neurogenesis and Reverse Cognitive Deficits in Alzheimer's Disease Model via Canonical Wnt/β-Catenin Pathway by Tiwari SK1, Agarwal S, Seth B, Yadav A, Nair S, Bhatnagar P, Karmakar M, Kumari M, Chauhan LK, Patel DK, Srivastava V, Singh D, Gupta SK, Tripathi A, Chaturvedi RK, Gupta KC.( PubMed )
(15) Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study by Ringman JM1, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, Gylys KH, Badmaev V, Heath DD, Apostolova LG, Porter V, Vanek Z, Marshall GA, Hellemann G, Sugar C, Masterman DL, Montine TJ, Cummings JL, Cole GM.( PubMed )
(16) Interaction of cinnamaldehyde and epicatechin with tau: implications of beneficial effects in modulating Alzheimer's disease pathogenesis by George RC1, Lew J, Graves DJ.( PubMed )
(17) Cinnamon extract inhibits tau aggregation associated with Alzheimer's disease in vitro by Peterson DW1, George RC, Scaramozzino F, LaPointe NE, Anderson RA, Graves DJ, Lew J.( PubMed )
(18) Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models by Frydman-Marom A1, Levin A, Farfara D, Benromano T, Scherzer-Attali R, Peled S, Vassar R, Segal D, Gazit E, Frenkel D, Ovadia M( PubMed )
(19) Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer's disease. by Chonpathompikunlert P1, Wattanathorn J, Muchimapura S.( PubMed )
(20) Preparation, characterization, in vivo and biochemical evaluation of brain targeted Piperine solid lipid nanoparticles in an experimentally induced Alzheimer's disease model by Yusuf M1, Khan M, Khan RA, Ahmed B.( PubMed )
(21) Green tea polyphenols protect against okadaic acid-induced acute learning and memory impairments in rats by Li H1, Wu X1, Wu Q1, Gong D1, Shi M1, Guan L1, Zhang J1, Liu J1, Yuan B1, Han G2, Zou Y3( PubMed )
(22) Neuroprotective effects of resveratrol and epigallocatechin gallate polyphenols are mediated by the activation of protein kinase C gamma. Menard C1, Bastianetto S2, Quirion R3( PubMed )
(23) Octyl gallate markedly promotes anti-amyloidogenic processing of APP through estrogen receptor-mediated ADAM10 activation by Zhang SQ1, Sawmiller D, Li S, Rezai-Zadeh K, Hou H, Zhou S, Shytle D, Giunta B, Fernandez F, Mori T, Tan J.( PubMed )
(24) Caffeine and coffee as therapeutics against Alzheimer's disease by Arendash GW1, Cao C.(PubMed)
(25) Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice by Arendash GW1, Mori T, Cao C, Mamcarz M, Runfeldt M, Dickson A, Rezai-Zadeh K, Tane J, Citron BA, Lin X, Echeverria V, Potter H.( PubMed )
(26) The role of ryanodine receptor type 3 in a mouse model of Alzheimer disease by Liu J1, Supnet C2, Sun S1, Zhang H1, Good L3, Popugaeva E4, Bezprozvanny I5.( PubMed )
(27) Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice by Arendash GW1, Mori T, Cao C, Mamcarz M, Runfeldt M, Dickson A, Rezai-Zadeh K, Tane J, Citron BA, Lin X, Echeverria V, Potter H.( PubMed )
(28) Caffeine and coffee as therapeutics against Alzheimer's disease by Arendash GW1, Cao C.
(P ubMed )
(29) Red wine micronutrients as protective agents in Alzheimer-like induced insult by Russo A1, Palumbo M, Aliano C, Lempereur L, Scoto G, Renis M.( PubMed )
(30) rion protein-mediated toxicity of amyloid-β oligomers requires lipid rafts and the transmembrane LRP1 by Rushworth JV1, Griffiths HH, Watt NT, Hooper NM( PubMed )
(31) Novel role of red wine-derived polyphenols in the prevention of Alzheimer's disease dementia and brain pathology: experimental approaches and clinical implications by Pasinetti GM.(P ubMed )
(32) The polyphenol oleuropein aglycone protects TgCRND8 mice against Aß plaque pathology by Grossi C1, Rigacci S, Ambrosini S, Dami TE, Luccarini I, Traini C, Failli P, Berti A, Casamenti F, Stefani M( PubMed )
(33) Oleuropein aglycone protects transgenic C. elegans strains expressing Aβ42 by reducing plaque load and motor deficit by Diomede L1, Rigacci S, Romeo M, Stefani M, Salmona M( PubMed )
(34) Olive-oil-derived oleocanthal enhances β-amyloid clearance as a potential neuroprotective mechanism against Alzheimer's disease: in vitro and in vivo studies by Abuznait AH1, Qosa H, Busnena BA, El Sayed KA, Kaddoumi A( PubMed ).
(35) Extra virgin olive oil improves learning and memory in SAMP8 mice by Farr SA1, Price TO, Dominguez LJ, Motisi A, Saiano F, Niehoff ML, Morley JE, Banks WA, Ercal N, Barbagallo M.( PubMed )
(36) Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease by Dacks PA1, Shineman DW, Fillit HM.(P ubMed )
(37) Nutrient intake and plasma β-amyloid by Gu Y1, Schupf N, Cosentino SA, Luchsinger JA, Scarmeas N.( PubMed )
(38) Diets involved in PPAR and PI3K/AKT/PTEN pathway may contribute to neuroprotection in a traumatic brain injury by Kitagishi Y1, Matsuda S.( PubMed )
(39) Combinatorial treatment of tart cherry extract and essential fatty acids reduces cognitive impairments and inflammation in the mu-p75 saporin-induced mouse model of Alzheimer's disease.
Matchynski JJ1, Lowrance SA, Pappas C, Rossignol J, Puckett N, Sandstrom M, Dunbar GL.( PubMed )
II. Types of Herbs Reduced risk of Alzheimer's disease
Strong evidences emerged in epidemiological studies suggested that certain herbs(2) may have potential in reduced risk and treatments of Alzheimer's disease but geographic source of the plant material, climatation, and time of harvest may effect their effectiveness. It is understandable that commercially available herbal medicinal products with the same herbal ingredients vary in their content and concentration of chemical constituents when compared between manufacturers.
1. Ginkgo biloba
Ginkgo biloba is oldest living tree species, genus Ginkgo, belonging to the family Ginkgoaceae, native to China, from temperate zone to subtropical zone and some parts of north America. It Has been used in traditional herbal medicine in treating impotence, memory loss,respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting.
Extracts of the leaves of the maidenhair tree, Ginkgo biloba, in identified trails on 26 June 2002 through a search of the CDCIG Specialized Register which contains records from all main medical databases, showed a positive effect of Ginkgo biloba in improvement of cognition and function(3). Study from Hospital St. Naum, Sofia, in enrolled 96 outpatients, aged 50 years or above, who met the NINCDS/ADRDA criteria for probable AD, showed no significance effect in either EGb 761(R)(Ginkgo biloba extract) and donepezil, but the result of the combination of 2 both substances are efficacy in treatment in patients with AD and neuropsychiatric features(4). But in the study of the same extract, Maria-Hilf Hospital Krefeld, Krefeld indicated that EGb 761® improved cognitive functioning, neuropsychiatric symptoms and functional abilities in both types of dementia namely Alzheimer's disease and vascular dementia(5)(6).
Ginseng is a slow-growing perennial plants with fleshy roots, the genus Panax, belonging to the family Araliaceae. Depending to the climate where it grows, ginseng can be classified mainly into Panax ginseng Asian ginseng (root), Red ginseng, wild ginseng, American ginseng (root).
In an open-label study, conducted by Seoul National University Hospital, Ginseng improved ADAS and MMSE scores declined and may be considered as clinically effective in the cognitive performance of AD patients(7). Other study also showed the effect of KRG on cognitive functions which was sustained for 2 yr follow-up and may be an indication of a feasible efficacy of long-term follow-up for Alzheimer's disease(9). Korean red ginseng (KRG) in high doses, significant improved on the ADAS and CDR after 12 weeks(8). Unfortunately, Study by the Korea Institute of Oriental Medicine, on Mini-Mental Status and the Alzheimer's Disease Assessment Scale (ADAS)-cognitive, showed inconclusive in the result of the efficacy of Ginseng(10).
3. Gotu Kola
Gotu Kola also known as centella, is a annual plant of the genus, belonging to the family Mackinlayaceae, native to India, Sri Lanka, northern Australia, Indonesia, Iran, Malaysia, Melanesia, Papua New Guinea. The herb has been used in traditional medicine to treat nervous disorders, epilepsy, senility, premature aging, etc.
Centella asiatica (CA), commonly named gotu kola water extract of CA (GKW), in the Tg2576 mouse, a murine model of AD with high β-amyloid burden, showed to attenuated β-amyloid-associated behavioral abnormalities and protected SH-SY5Y cells and MC65 human neuroblastoma cells from toxicity(11) through the impact of the amyloid cascade altering amyloid beta pathology(12) and colchicine-induced memory impairment and oxidative damage(13).
4. Lemon Balm
Lemon Balm is is a perennial plant in the genus Melissa, belonging to the family Lamiaceae, native to southern Europe and the Mediterranean region. The herb has been used in traditional medicine to treat nervous complaints, lower abdominal disorders and as anti-inflammatory, antivirus, antibacterial agent.
Aromatherapy consisted of the use of rosemary and lemon essential oils in the morning, and lavender and orange in the evening showed significant improvement in personal orientation related to cognitive function on both the GBSS-J and TDAS after therapy(14). In a study of 20 healthy, young participants received single doses of 600, 1000, and 1600 mg of encapsulated dried leaf at 7-day intervals, indicated that doses of Melissa officinalis at or above the maximum employed here can improve cognitive performance and mood(15). Other study of a standardized M. officinalis extract (300 mg, 600 mg), indicated a significantly increased self-ratings of calmness and reduced self-ratings of alertness and negated the negative mood effects of the DISS(16)(17).
Rosemary is a perennial herb with fragrant, evergreen, needle-like leaves, the genus Rosmarinus, belonging to the family Lamiaceae. Its fresh and dried leaves has been used frequently in traditional Mediterranean cuisine and as flavor foods while barbecuing. Rosnary has been used in traditional medicine as an antiseptic, antioxidant, and antispasmodic agent to treat circulatory problem, eczema, rheumatism, muscle pain, etc.
Carnosic acid (CA), a chemical compound found in rosemary and sage, reduces Aβ production, at least partially, by activating TACE in human astroglial cells(18) and the University of Tlemcen, also indicated that CA may be potential against Acetylcholinesterase (AChE) which gradual and irreversible declines in cognitive functions in AD patients(19). In an aromatherapy consisted of the use of rosemary and lemon essential oils in the morning, and lavender and orange in the evening, showed that the combination may have some potential for improving cognitive function, especially in AD patients(20).
6. Chinese Cat's claw
Chinese Cat's claw also known as Gou Teng, Uncaria rhynchophylla, a genus of Uncaria, belonging to the family Rubiaceae, native to China. The herb is said to consist neuroprotective, anticonvulsive, sedative and antipsychotic effect.
Mice given a subcutaneous injection of D-gal (50 mg/kg) and orally administered Uncaria rhynchophylla (EUR) (100, 200, or 400 mg/kg) daily for 8 weeks, significantly increased exploratory behavior (assessed by an open-field test) and improved spatial learning and memory function (assessed by the Morris water maze test) as well as increasing the levels of acetylcholine and glutathione and decreasing the activity of acetylcholinesterase and the level of malondialdehyde in the brains through enhancement of the antioxidant status of brain tissue(21. Center for Asian Traditional Medicine Research, Tohoku University also indicated that Uncaria rhynchophylla has remarkably inhibitory effects on the regulation of Abeta fibrils(22), a significant step in the pathogenesis of Alzheimer's disease.
7. Polygala tenuifolia
Polygala tenuifolia also known as Yuan Zhi is a genus Polygala, belonging to family Polygalaceae, native to China. The herb has been used in TCM to insomnia, forgetfulness, emotional and disorientation with abundance of phlegm, seizures, anxiety, listlessness, boils, abscesses, sores,etc.
Extract of dried root of Polygala tenuifolia Willdenow was found to provide some protective effects against neuronal death and cognitive impairments in Alzheimer's disease (AD), in the study by the Seoul National University(23). Tenuigenin, a crude extract of Polygala tenuifolia Willd. significantly decreased Abeta secretion from COS-7 cells without altering the ratio of Abeta1-40 and Abeta-42 (in differentiation of change in Abeta metabolism) probably through inhibition of the deposit of beta-site APP cleaving enzyme(causing increased levels of amyloid beta (Abeta) peptide, an early and critical feature of Alzheimer's disease)(24) or inhibited the secretion of A beta in SH-SY5Y APP 695 cells (amyloid precursor protein (APP)) via BACE1 inhibition(reduced risk of the build up of beta-amyloid and slow or stop Alzheimers disease)(25). Ninjin-yoei-to (NYT; Ren-shen-yang-rong-tang in Chinese formula, among 14 kinds of component herbs in NYT, the roots of Polygala tenuifolia extracts increased nerve growth factor NGF levels from the astrocytes(star shaped glial cells with function of support to neurons and clean up debris within the brain)(26).
8. Salvia officinalis (Sage)
Sage is a ornamental plant of the genus Salvia, belonging to family Lamiaceae, native to the Central and South America, Central, Eastern Asia and Mediterranean. The herb has been used in traditional medicine as carminative, antiperspirant, antispasmodic, astringent, antiseptic, and antibiotic agent and to calm the central nervous system, treat spasms in smooth and skeletal muscles, relieve digestive problems, regulate menstruation, etc.
According to the Northumbria University, extracts Salvia officinalis exerted its anti-oxidant, estrogenic, anti-inflammatory properties, to inhibited butyryl- and acetyl-cholinesterase (to prevent impeded neurotransmission)(27). Rosmarinic acid from Sage, in mild to moderate Alzheimer's disease (AD), enhanced the neuroprotective effect of sage against Abeta-induced toxicity, through inhibition of reactive oxygen species formation, lipid peroxidation, DNA fragmentation, caspase-3 activation(cell apoptosis), and tau protein hyperphosphorylation(neurofibrillary degeneration)(28)
9. Papaver somniferum (Opium poppy)
Papaver somniferum is a genus of Papaver, belonging to the family Papaveraceae, native to the Mediterranean Basin, Southeastern Europe, and Western Asia. The herb has been used in folk medicine for treating asthma, stomach illnesses, and bad eyesight.
Opium poppy exerted it neuroprotective effect through interaction of alkaloid opioids of herb with endogenous opiate receptors in the brain, according to Medical Research Council, Newcastle General Hospital(29). Some alkaloids isolated from plants, or are derived from templates of compounds from plant sources have been in clinical use for treatment of cognitive disorders(30).
10. saffron (Crocus sativus)
Saffron is a spice derived from the flower of Crocus sativus which is a genus Crocus, belonging to the family Iridaceae, native to Southeast Asia.
Saffron extract, showed moderated AChE inhibitory activity, verified by in silico docking studies(31) and some promising effects in clinical studies with dementia patients(32). In a double-blind, placebo-controlled Tehran University of Medical Science study, suggested a positive mild to moderate Alzheimer's disease effect through inhibition of the aggregation and deposition of amyloid β in the human brain(33). Crocin isolated from Saffron, in Alzheimer's disease induced by intracerebroventricular (icv) streptozocin (STZ) in male rats, significantly attenuated learning and memory impairment(34).
11. Bacopa monnieri
Bacopa monnieri is a genus Bacopa, belonging to family Plantaginaceae, native to the wetlands of southern India and Australia. The herb has been used in Indian traditional medicine as a neurological tonic and cognitive enhancer.
In intracerebroventricular administration of colchicine induced cognitive impairment in rats, Bacopa monnieri decreased in activity of antioxidant enzyme, reversed memory impairment and altered activity of membrane bound enzymes(35). Other study of Bacopa monnieri extract indicated an improvement of the escape latency time (p