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Diseases of Central Nervous system
Dementia
About 5-8% of all people over the age of 65 have some form of dementia, and this number doubles every five years above that age. Dementia is the loss of mental ability, severe enough to interfere with people's every life and Alzheimer's disease is the most common type of dementia in aging people.
V. Treatments
A. In herbal medicine perspective
1. Ginkgo Biloba(bai Guo)
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(592). The herb been used in traditional herbal medicine in treating impotence, memory loss, respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting(591).
a. The memory enhancing effects
Capsules containing 60 mg of a standardised extract of Ginkgo biloba (GK501) and 100 mg of a standardised extract of Panax ginseng (G115) showed significantly to improve an Index of Memory Quality(593), including learning and memory but not working and long-term memory(596). Its extract, in the logical memory test and nonsense picture recognition exhibits improvement of 58.62% logical memory in compared to baseline(594). Comercial extract Ginkgo biloba EGb 761 enhanced certain neuropsychological/memory processes of cognitively in older adults, 60 years of age and over(595).
b. Cognitive performance
Administration of single doses (120, 240, 360 mg) of standardised Ginkgo biloba extract (GBE), according to Northumbria University, showed to improve cognitive performance, including speed of attention, accuracy of attention, secondary memory, working memory, speed of memory, quality of memory(597). Combination of standardised extracts of Ginkgo biloba (GK501, Pharmaton SA) and Ginseng (G115, Pharmaton SA) administration showed a consistent effect on mood and aspects of cognitive performance ("quality of memory", "secondary memory", "working memory", "speed of memory", "quality of attention" and "speed of attention") in doeses depend-manner(598). On acute cognitive effects, Ginkgo biloba extract (GBE) with soy-derived phospholipids, improved secondary memory performance and significantly increased speed of memory task performance in comparision to post-dose testing sessions(599).
c. Cognitive impairment
Extracts of the leaves of Ginkgo biloba showed to improve a range of conditions including memory and concentration problems, confusion, depression, anxiety, dizziness, tinnitus and headache, recognition, regeneration, understanding, and recitation(603), probably thought its action in increasing blood supply by dilating blood vessels, reducing blood viscosity, modification of neurotransmitter systems, and reducing the density of oxygen free radicals(600).
EGb761, acommercuial product of Ginkgo biloba at 240 mg/day, shawed to stabilize or slow decline in cognition, function, behavior, at 22-26 weeks (602).
Accoording to University of Oxford, the use of v ofr treatement of cognitive impairment appeared to be safe with no excess side effects compared with placebo, but with inconsistent results(601).
d. Etc.
References
(591) http://thedao.com/ginkgo.htm
(592) http://en.wikipedia.org/wiki/Ginkgo_biloba
(593) http://www.ncbi.nlm.nih.gov/pubmed/11140327
(594) http://www.ncbi.nlm.nih.gov/pubmed/22704410
(595) http://www.ncbi.nlm.nih.gov/pubmed/12404671
(596) http://www.ncbi.nlm.nih.gov/pubmed/16740301
(597) http://www.ncbi.nlm.nih.gov/pubmed/17902186
(598) http://www.ncbi.nlm.nih.gov/pubmed/11842916
(599) http://www.ncbi.nlm.nih.gov/pubmed/17457961
(600) http://www.ncbi.nlm.nih.gov/pubmed/19160216
(601) http://www.ncbi.nlm.nih.gov/pubmed/12519586
(602) http://www.ncbi.nlm.nih.gov/pubmed/25114079
(603) http://www.ncbi.nlm.nih.gov/pubmed/24758078
2. Lemon balm
Lemon Balm 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(604), lower abdominal disorders(605) and as anti-inflammatory(608), antivirus(606), antibacterial agent(607).
a. Behavioral and psychological symptoms
According to Newcastle University, lemon balm showed to alleviate behavioral and psychological symptoms in patient with dementia (BPSD)(609), including anxiety(614). Lozenge, containing lavender oil, extracts from hops, lemon balm and oat showed to induce a state of relaxation and regeneration for better cope with psychological and emotional stress(610)(611) and attenuation of mood and anxiety(612). In behavior symttoms, administraion of combined valerian root and lemon balm extracts, improved symptoms of poor ability to focus decreased from 75% to 14%, hyperactivity from 61% to 13%, and impulsiveness from 59% to 22% as well as general social behavior, sleep symptoms in children(613). On laboratory-induced psychological stress, the standardized M. officinalis extract, a significant increase in the speed of mathematical processing, with no reduction in accuracy were observed(617).
b. Cognitive performance and mood
A standardised M. officinalis preparation administered showed significantly in eradicated mood change and cognitive impairment(614), according to joint study lead by Swinburne University. Acute administration of Melissa officinalis (lemon balm) in highest dose, cognition and mood in in both Secondary Memory and Working Memory factors(615)(616). The effective of the herb, probably through its function in Modulation of mood and cognitive performance through lowering both nicotinic and muscarinic binding in healthy humans(616). Due to different preparations derived from the same plant species, some researchers suggested that the effectiveness may exhibit different properties depending on the process used for the sample preparation(616).
c. Etc.
References
(604) http://www.ncbi.nlm.nih.gov/pubmed/21076869
(605) http://www.ncbi.nlm.nih.gov/pubmed/19023806
(606) http://www.ncbi.nlm.nih.gov/pubmed/18693101
(607) http://www.ncbi.nlm.nih.gov/pubmed/24283351
(608) http://www.ncbi.nlm.nih.gov/pubmed/22567036
(609) http://www.ncbi.nlm.nih.gov/pubmed/22070157
(610) http://www.ncbi.nlm.nih.gov/pubmed/15546807
(611) http://www.ncbi.nlm.nih.gov/pubmed/15272110
(612) http://www.ncbi.nlm.nih.gov/pubmed/16444660
(613) http://www.ncbi.nlm.nih.gov/pubmed/24837472
(614) http://www.ncbi.nlm.nih.gov/pubmed/25360512
(615) http://www.ncbi.nlm.nih.gov/pubmed/12062586
(616) http://www.ncbi.nlm.nih.gov/pubmed/12888775
(617) http://www.ncbi.nlm.nih.gov/pubmed/15272110
3. Lavender
Lavender is a flower plant of the genus Lavandula, belonging to the family Lamiaceae, native to Asia. The herb has been used in traditional medicine as antimicrobial, anti-inflammatory and mood alleviating(618), and burns and insect bites effects(623), as well as depression, stress and mild anxiety(621) probably through its phytochemicals(constituents (-)-linalool, (+)-α-pinene and (+)-limonene ) in modulation of the immune and neuroendocrine system by interfering with metabolism of tryptophan(618).
a. Spatial performance
Lavender extract (LE, in AD animal model showed effectively in improvement of spatial performance, through atentuation of Aβ production in histopathology of hippocampus(619) which involved in memory forming, organizing, and storing. Its aqueous extract of lavender (Lavandula angustifolia), also significantly improved the performance of control and reverse spatial learning amd memory deficits(621) in AD rats(620). Inhaled lavender oil, oxidative stress induced rat, exhibited neuroprotective effects through its potent antioxidant and antiapoptotic activities(622).
b. Behavioural symptoms
Lavender aromatherapy, according to Kongju National University, is effective on emotions and aggressive behavior of elderly with dementia of the Alzheimer's type(624)and reduced disruptive behaviour in people with dementia(625). In agitated behaviour in severe dementia, 2% lavender oil aromatherapy stream administered on the ward for a two hour period, showed a modest effects in compared with placebo(626). The effectiveness of the herb in reduced behaviours in individuals with dementia potentially provide a safer intervention rather than reliance on pharmacology alone. The study's findings will translate easily to other countries and cultures(627).
c. Cognitive performance and Mood disorders
Aromatherapy applied to 28 elderly people with dementia, 17 of whom had Alzheimer's disease (AD), showed significant improvement in personal orientation related to cognitive function on both the Gottfries, Brane, Steen scale (GBSS-J)and Touch Panel-type Dementia Assessment Scale (TDAS), according to Tottori University(628) and emotions and aggressive behavior of elderly with dementia, according to Kongju National University(629). In emotional parameters, lavender essential oil also significantly enhance mood responses, including anxiety(631)(633) and depression(632)(634) probably through its relaxing effect(630).
d. Etc.
References
(618) http://www.ncbi.nlm.nih.gov/pubmed/25515049
(619) http://www.ncbi.nlm.nih.gov/pubmed/25561935
(620) http://www.ncbi.nlm.nih.gov/pubmed/21441971
(621) http://www.ncbi.nlm.nih.gov/pubmed/22402245
(622) http://www.ncbi.nlm.nih.gov/pubmed/23351960
(623) http://www.ncbi.nlm.nih.gov/pubmed/?term=lavender+burns+and+insect+bites+effects
(624) http://www.ncbi.nlm.nih.gov/pubmed/15860944
(625) http://www.ncbi.nlm.nih.gov/pubmed/23837414
(626) http://www.ncbi.nlm.nih.gov/pubmed/11994882
(627) http://www.ncbi.nlm.nih.gov/pubmed/20649945
(628) http://www.ncbi.nlm.nih.gov/pubmed/20377818
(629) http://www.ncbi.nlm.nih.gov/pubmed/15860944
(630) http://www.ncbi.nlm.nih.gov/pubmed/22612017
(631) http://www.ncbi.nlm.nih.gov/pubmed/19968674
(632) http://www.ncbi.nlm.nih.gov/pubmed/24559818
(633) http://www.ncbi.nlm.nih.gov/pubmed/19258850
(634) http://www.ncbi.nlm.nih.gov/pubmed/16520572
4. Huperzine A
Huperzine A, a chemical made from the plant Huperzia serrata have been studied for its effect on patient of dementia with conflict results
1. Cognitive effects
In induced Alzheimer's disease animal study, Huperzine A showed a significant effect in inhibited acetylcholinesterase, derived from forebrain, hippocampus, cortex and cerebellum(635), through neuron protective effects and enhanced glutamatergic functions(635). In mild to moderate vascular dementia (VaD) patients, The medicine also improved the cognitive function with serious adverse events(636). But according to University of California,, in a phase II trial of huperzine A, regardless to doses, huperzine A did not demonstrate cognitive effect in patients with mild to moderate AD(637). According to Beijing University of Chinese Medicinealthough Huperzine A showed a beneficial effects on improvement of cognitive function, daily living activity in global clinical assessment in participants with Alzheimer's disease, the findings should be interpreted with caution due to the poor methodological quality of the included trials(638).
b. Inhibitiobn of amyloid plaque burden and oligomeric β-amyloid (Aβ)
Huperzine A, showed to reduce in Aβ levels and Aβ burden in AD brain, through activation of Wnt signaling(regulate cell-to-cell interactions) and targeting of the Wnt/β-catenin signaling pathway in various components in contribution to disease, (639), modulation of amyloidogenic and nonamyloidogenic pathways(640), reduction of iron in the brain(641) via a multi-target mechanism(642).
c. Mild to moderate vascular dementia (VaD) and Alzheimer's disease
In patients with mild to moderate vascular dementia (VaD), Huperzine A significantly improve the cognitive function in mini-mental state examination (MMSE), clinical dementia rating (CDR), and activities of daily living (ADL) scores(643)(644).
In patients with Alzheimer's disease (AD), Huperzine A also showed improvement in memory function and cognitive enhancement at a dose of 0.4 mg using MMSE, MQ, ADAS-COG, and ADL tests(645); against organophosphate (OP) intoxication and reduction of glutamate-induced cell death(646). According to Georgetown University Hospital, the antioxidant and neuroprotective properties of Huperzine A suggest that it may be useful as a disease-modifying treatment for Alzheimer's disease (AD)(647).
Due to data supporting its use are limited by weak study design, theMassachusetts College of Pharmacy and Health Sciences-Worcester/Manchester suggested that randomized, placebo-controlled trials are necessary to establish the role of huperzine A in the treatment of AD(648).
d. Etc.
References
(635) http://www.ncbi.nlm.nih.gov/pubmed/9141073
(636) http://www.ncbi.nlm.nih.gov/pubmed/21833673
(637) http://www.ncbi.nlm.nih.gov/pubmed/21502597
(638) http://www.ncbi.nlm.nih.gov/pubmed/24086396
(639) http://www.ncbi.nlm.nih.gov/pubmed/?term=Huperzine+A+Wnt%2F%CE%B2-catenin+signaling+pathway
(640) http://www.ncbi.nlm.nih.gov/pubmed/22002568
(641) http://www.ncbi.nlm.nih.gov/pubmed/24332448
(642) http://www.ncbi.nlm.nih.gov/pubmed/15956816
(643) http://www.ncbi.nlm.nih.gov/pubmed/?term=Huperzine+A+and+Mild+to+moderate+vascular+dementia+(VaD)
(644) http://www.ncbi.nlm.nih.gov/pubmed/24639880
(645) http://www.ncbi.nlm.nih.gov/pubmed/21766442
(646) http://www.ncbi.nlm.nih.gov/pubmed/12895686
(647) http://www.ncbi.nlm.nih.gov/pubmed/18230054
(648) http://www.ncbi.nlm.nih.gov/pubmed/19240260
5. Bacopa
Commonly known as Waterhyssop or Water Hyssop, the herb is a semi-woody plants, genus of Hyssopus, belonging to the family Lamiaceae, native to the east Mediterranean to central Asia, used in traditional medicine as an antibiotic(660)(659), carminative, antispasmodic, antifungal(661), and antiseptic(661)(662) agent and to treat bronchitis(663), asthma(664), digestive ailments(665)(668), insomnia(666), diabetes(667), edema(669)(670), etc.
a. Increases Cerebral Blood Flow
In cerebral blood flow (CBF), Bacopa monnieri's promoting blood flow through its procognitive effect in comparison via dose-dependent hypotensive actions (671), with Ginkgo biloba and donepezil(671)may ne a potential attenuation of dementia, Parkinson's disease, and epilepsy(672).
a. Increases Cerebral Blood Flow
In cerebral blood flow (CBF), Bacopa monnieri's promoting blood flow through its procognitive effect in comparison via dose-dependent hypotensive actions (671), with Ginkgo biloba and donepezil(671)may ne a potential attenuation of dementia, Parkinson's disease, and epilepsy(672).
b. Ethnobotanical treatment
Bacopa, ethnobotanically, may be used as brain tonification(676) and to treat various diseases(673), including Alzheimer's disease
through its phytochemicals in alleviation of AD pathology and associated symptoms(674). According to sity System HSC College of Medicine, Bacopa monniera extract (BME), administered starting at 2 months of age for either 2 or 8 months in test mice, significant lowers Abeta 1-40 and 1-42 levels in cortex by as much as 60%, and reverses Y-maze performance and open field hyperlocomotion behavioral changes(675). Its natural products (galantamine and rivastigmine), also has been used pharmaceutically for cognitive and behavioural and psychological symptoms of dementia (BPSD)(673).
c. Cognitive performance, anxiety, and depression
c. Cognitive performance, anxiety, and depression
In olfactory bulbectomized mice, alcoholic extract of Bacopa monnieri (L.) showed to ameliorate memory and emotional deficits(678) and enhanced cognitive performance(679) through its protection of cholinergic systems from OBX-induced neuronal damage(677). In normal healthy participants, the herb also attenuated stress reactivity and mood, through its adaptogenic and nootropic effects, probably via reduction in cortisol levels(680). According to National College of Natural Medicine, standardized dry extract of Bacopa monnieri, promoted the improvement depression scores, combined state plus trait anxiety scores,with few adverse events, primarily stomach(681)
d. Etc.
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d. Etc.
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6. Other potential herbs
Herbs used in the treatment and prevention of dementia(682)(683) in traditional medicine, may be due to their effectiveness of phytochemicals in attenuation of oxidative stress and neuro inflammation via neuroglial activation(683).
According to University of Wollongong, herbs and spices, containing high amount of phytochemicals in traditional history of use, with strong roles in cultural heritage, may have a distinguished effect in cognitive decline associated with ageing and the acute effects of psychological and cognitive function(684), probably through active ingredients of spices in modulation of neural response in the peripheral nervous system, via interaction with TRP channel/receptors(685).
Phytochemicals have been studied intensively including
1. Cannabinoids (e.g. cannabidiol) from Cannabis sativa, may be emerging as potential therapeutic agents for treatment of symptoms of dementia(686)(687). In Alzheimer's disease. the phytochemicals have found effective in against multifactorial illnesses as Alzheimer's disease, through inhibition of BuChE(689) and AChE(690) enzymes by a non-competitive or mixed mechanism(688).
Resveratrol (occurs in various plants) showed to improved cognition and reduces oxidative stress, by promoting learning and memory ability in vascular dementia(692) and decreased malonyldialdehyde levels(691). In Alzheimer's Disease, the phytochemical exerted its neuroprotective effect(694)(695), in decreased Aβ accumulation, tau protein phosphorylation, oxidative stress(693), and may be used for aging population in the prevention of various age-related neurological disorders(694).
2. Curcumin (from turmeric [Curcuma longa]), in pharmacological activities, besides promoted cognition and mood in a healthy older population(695), it also exhibited beneficial role in several neurodegenerative disorders(696) against administered streptozotocin (STZ)induced dementia model(696)(698), probably through its antioxidant effect(697). In Alzheimer's Disease, The herb showed in reversed cognitive deficits, through its function in decreased GSK-3β levels related to Alzheimer's Disease(Glycogen synthase kinase 3, a protein(699)), and increased promoter activity of the TCF/LEF in binding DNA(600) and cyclin-D1(a protein) in regulating cell cycle progression(701).
3. Crocetin, a phytochemical found in Saffron (Crocus sativus), showed to protect cerebrocortical and hippocampus neurons against ischemia, by improving spatial learning memory after chronic cerebral hypoperfusion in animal study(703) through its antioxidant effects(704) in decreased oxidative stress(704). According to The University of Tokyo, the effectiveness of the herbal phytochemicals also crocetin and crocin, enhanced learning behaviour and promoted memory recall(705). In severe Alzheimer's Disease and mild-to-moderate Alzheimer's disease patients, saffron extract showed to be comparable with memantine in reducing cognitive decline in 1 year(706) and reduce cognitive decline in 22 weeks administration(707), respectively.
4. Ginseng (Panax species), showed to be beneficiary on age-related cognitive impairments
through the activities of its number of ginsenosides(708) and Non-ginsenoside nicotinic agents(709).
5. Sage (Salvia species), may also be used as a potential novel natural treatments for the relief of some diseases including dementia, according to Shahid Beheshti University of Medical Sciences(710).
But according to Jodrell Laboratory, the use of such remedies in complex mixtures of different plants in traditional folk medicine may induce complication in interpretation of pharmacological activity and challenges for quality control(702).
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Sources
(682) http://www.ncbi.nlm.nih.gov/pubmed/23055633
(683) http://www.ncbi.nlm.nih.gov/pubmed/20657497
(684) http://www.ncbi.nlm.nih.gov/pubmed/17022438
(685) http://www.ncbi.nlm.nih.gov/pubmed/25359561
(686) http://www.ncbi.nlm.nih.gov/pubmed/24828945
(687) http://www.ncbi.nlm.nih.gov/pubmed/24624670
(688) http://www.ncbi.nlm.nih.gov/pubmed/24378710
(688) http://www.medscape.com/viewarticle/424604_5
(689) http://www.ncbi.nlm.nih.gov/pubmed/24378710
(690) http://www.ncbi.nlm.nih.gov/pubmed/25206513
(691) http://www.ncbi.nlm.nih.gov/pubmed/25206513
(692) http://www.ncbi.nlm.nih.gov/pubmed/24660032
(693) http://www.ncbi.nlm.nih.gov/pubmed/25525597
(694) http://www.ncbi.nlm.nih.gov/pubmed/19090994
(695) http://www.ncbi.nlm.nih.gov/pubmed/25315300
(694) http://www.ncbi.nlm.nih.gov/pubmed/25281824
(695) http://www.ncbi.nlm.nih.gov/pubmed/25277322
(696) http://www.ncbi.nlm.nih.gov/pubmed/20026275
(697) http://www.ncbi.nlm.nih.gov/pubmed/19705549
(698) http://www.ncbi.nlm.nih.gov/pubmed/21195590
(699) http://en.wikipedia.org/wiki/GSK-3
(700) http://en.wikipedia.org/wiki/TCF/LEF_family
(701) http://en.wikipedia.org/wiki/Cyclin_D1
(702) http://www.ncbi.nlm.nih.gov/pubmed/21639405
(703) http://www.ncbi.nlm.nih.gov/pubmed/23988025
(704) http://www.ncbi.nlm.nih.gov/pubmed/21774008
(705) http://www.ncbi.nlm.nih.gov/pubmed/10815004
(706) http://www.ncbi.nlm.nih.gov/pubmed/25163440
(707) http://www.ncbi.nlm.nih.gov/pubmed/19838862
(708) http://www.ncbi.nlm.nih.gov/pubmed/10189953
(709) http://www.ncbi.nlm.nih.gov/pubmed/21639405
(710) http://www.ncbi.nlm.nih.gov/pubmed/24860730
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