Saturday 21 February 2015

(4th edited )Most common diseases of Elders- Diseases of Central Nervous system(CNS): TCM treatments of Dementia Caused by Heart Qi Deficiency

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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
C. In traditional Chinese Medicine Perspective(*)
Based on Chinese ancient medical records. causes of dementia are the results of (*)
C.3. Deficiency of Qi, mainly due to
C.2.2. Heart (Yang) Qi deficiency
Heart  Qi deficiency is a condition of the inability of the heart in transportation of nutrients to body organs, including the brain through blood circulation. Prolong period of malnutrition of brain cells may induce abnormal function of brain's cells in information transmitting  or death of neurons, causing cognitive impairment(844), including learning and memory deficits(842) and changes in brain tissue and behavior patterns(843)(842).
Herbal medicine for Heart Qi deficiency
1. Dan shen
Dan Shen is also known as Red Sage Root with taste of   the bitter and slightly cold in nature, used in TCM as antithrombotic(845), antihypertonic (lowering blood pressure)(846), antimicrobial(847), anti-inflammatory(848)(849), agent and to treat coronary and cerebrovascular disease, dysmenorrhea, amenorrhea, hepatitis, hepatocirrhosis, restlessness, insomnia, irritability,(850) etc., by enhancing the functions of heart and liver channels.

Phytochemicals
1. Cryptotanshinone
2. Hydroxytanshinone,
3. Methyltanshinonate
4. Methylene tanshiquinone
5. Przewatanshinquinone A
6. Przewatanshinquinone B
7. Miltirone
8. Dihydrotanshinone I
9. Tanshinol A
10. Tanshinol B
11. Tanshinol C,
12. Nortanshinone
13. 1, 2, 15, 16-tetrahydrotanshiquinone
14. Danshensuan A, B, C
15. Protocatechuic acid,
16. Protocatechuic aldehyde
17. Etc.


1.1. Dementia
According to Mashhad University of Medical Sciences, dan shen in the pharmacological effects on the central nervous system, showed to exert its neuroprotective activity through antiparkinsonian, relaxant, analgesic and  memory enhancing(850). In PC12 cells, combination application of salvianolic acid B (Sal B) and Ginkgo biloba extract EGb 761, effectively inhibited the formation of amyloid fibrils and protected PC12 cells(855) from beta-AP25-35-induced cytotoxicity and ROS accumulation(854).

1.2. Alzheimer's disease (AD)
Simple poly hydroxycinnamic acids and diterpenoid quinone, showed to improve cognitive deficits in mice model, through protection of neuronal cells, prevention of amyloid fibril formation and preformed amyloid fibril disaggregation related to Alzheimer's disease(851). Salvianolic acid B (Sal B)isolated from dan shen, in animal model, not only prevented Abeta-induced cytotoxicity(857) but also improved cognitive deficits and protection of neuronal cells(852), through its effects on suppressing the production of ROS, calcium flux, and apoptosis(853) and promoted amyloid precursor protein (APP) metabolism toward the non-amyloidogenic products pathway in cortical neuronal cell(856) and multifunctional machenisms(857). Compound Danshen Tablets (CDST), in rat model, exhibited spatial cognitive protection through decreased beta-APP expression in the cortex and hippocampus, detected via immunohistochemistry(859).

1.3.  In learning and memory impairment
In diabetic rats model, dan shen injection improved the learning and memory decline, through upregulation of expression of MKP-1 in reduced inflammation(861) under hyperglycemia(860). HX106N, a Chimese herbal formula, containing dan shen, in Aβ25-35 peptide mice, enhanced on memory impairment and oxidative stress through increased levels of heme oxygenase-1 (HO-1)(862). In a joint study of renowned institutions, in mouse model, myelophil, a combination of extracts taken from Astragali Radix and Salviae Miltiorrhizae Radix, significantly exhibited its anti-amnesic properties in  memory impairment, through the modulation of cholinergic activity(863). Tanshinones, a group of diterpenoids found in dan shen, improved learning and memory impairments, through its inhibitory effect on acetylcholinesterase(864)

1.4. In neuroprotective effects
Tanshinone IIA (Tan IIA), one of the major active constituents of dan shen exerted its neuroprotective effects, by inhibiting transcription and translation of genes involved AD development(858). In neurotoxicity of β-amyloid protein (Aβ) contributed Alzheimer's disease (AD), dan shen extract suppressed the increased intracellular reactive oxygen species levels, through deduction of decreased the protein expression involved in the development of neurodegenerative disease, including ADs(865). According to Eur J Pharmacol and University of Sydney, salvianolic acid B (SalB), in mouse model, exhibited neuroprotective effects in an amyloid β (Aβ) peptide-induced Alzheimer's disease, through its anti-inflammatory and anti-oxidative effects(866) and ameliorated cholinergic dysfunction- or Aβ(25-35)-induced memory impairment(867), respectively.
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Reprinted from Norton Journal, Volume I, Most Common Diseases of Ages of 50 Plus - Chapter of Diseases of Central Nervous system(CNS): Dementia - Treatments in Traditional Chinese Medicine by Kyle J. Norton 


References
(842) http://www.ncbi.nlm.nih.gov/pubmed/25313575
(843) http://www.ncbi.nlm.nih.gov/pubmed/24224039
(844) http://www.ncbi.nlm.nih.gov/pubmed/23391905
(845) http://www.ncbi.nlm.nih.gov/pubmed/20451955
(846) http://www.ncbi.nlm.nih.gov/pubmed/21855622
(847) http://www.ncbi.nlm.nih.gov/pubmed/25272827
(848) http://www.ncbi.nlm.nih.gov/pubmed/23469598
(849) http://www.ncbi.nlm.nih.gov/pubmed/25525444
(850) http://www.ncbi.nlm.nih.gov/pubmed/16619340
(851) http://www.ncbi.nlm.nih.gov/pubmed/24393583
(852) http://www.ncbi.nlm.nih.gov/pubmed/17964692
(853) http://www.ncbi.nlm.nih.gov/pubmed/16890202
(854) http://www.ncbi.nlm.nih.gov/pubmed/17039773
(855) http://www.ncbi.nlm.nih.gov/pubmed/22314911
(856) http://www.ncbi.nlm.nih.gov/pubmed/19154776
(857) http://www.ncbi.nlm.nih.gov/pubmed/23703159
(858) http://www.ncbi.nlm.nih.gov/pubmed/24859152
(859) http://www.ncbi.nlm.nih.gov/pubmed/22594104
(860) http://www.ncbi.nlm.nih.gov/pubmed/25187809
(861) http://www.ncbi.nlm.nih.gov/pubmed/22320295
(862) http://www.ncbi.nlm.nih.gov/pubmed/24694662
(863) http://www.ncbi.nlm.nih.gov/pubmed/24690775
(864) http://www.ncbi.nlm.nih.gov/pubmed/17714702
(865) http://www.ncbi.nlm.nih.gov/pubmed/24932696
(866) http://www.ncbi.nlm.nih.gov/pubmed/23461850
(867) http://www.ncbi.nlm.nih.gov/pubmed/21903108 

2. Ren shen (Ginseng)
Ren Shen is a smells aromatic, tastes sweet and slightly warm herbs, also known as Gingshen, used in TCM as improved immune system(868)(869), Anti Cancer(870)(871), Anti aging(872)(873), Anti stress(874)(875), anti Erectile dysfunction(876)(877), etc. agent and to generates fluids and reduce thirst and symptoms of diabetes(878)(879), for xinqixu (heart qi deficient) related coronary heart disease (CHD)(880)(881), anxiety(882)(883), insomnia(884)(885), depression(886)(887), neurodegenertive disorders(888)(889)(890), bleeding in the vagina not during period(891), seizures(892)(893), chronic fatigue(894)(895), etc. as it strongly tonifies Original Qi, the Spleen and the Lungs, promotes generation of Body Fluids, calms thirst and the Mind,(896) etc. by enhancing the functions of spleen and lung channels(897).

Ingredients
1. Saponins
2. Panaxynol
3. Ginsenyne
4. Alpha pansinsene
5. Beta pansinsene
6. Beta farnesene
7. Bicyclogermacrene
8. Beta elemene
9. Gama elemene
10. Alpha neodovene
11. Beta neodovene
12. Alpha humulene
13. Beta humulene
14. Ccaryophyllene
15. Beta gurjunene
16. Alpha gurjunene
17. Alpha selinene
18. Beta selinene
19. Gama selinene
20. Selin-4, alpha guaiene
21. Gama cubebene
22. Beta patchoulene
23. Hepatadecanol-1
24. Etc.

Herbal ren shen used in the treatment and prevention of dementia(898) in traditional Chinese medicine, may be due to its effectiveness of phytochemicals in ameliorated amyloid pathology(899)(900) and related cognitive deficits(901). In aging related dementia, based on the history of use, and pharmacological investigation, ren shen showed a strong evidence in cognitive improvement, through cholinesterase inhibitory activity and cholinergic function(902). According to Beijing University of Chinese Medicine, combination extract of Renshen (Panax Ginseng), Yinyanghuo (Herba Epimedii Brevicornus), Yuanzhi (Radix Palygalae) and Jianghuang (Rhizoma Curcumae Longae) (GEPT) exhibited neuroprotecting mechanism in preventing and treating of AD(903).

2.1. In Alzheimer's disease
Alzheimer's disease is a brain disorder named after German physician Alois Alzheimer. The disease destroys brain cells involved inflammation, mitochondrial dysfunction or oxidative stress(904), causing problems with memory, thinking and behavior severe(904) enough to affect language communication(905), memory(906), lifelong hobbies or social life(907).
Ginseng extracts, in Alzheimer's disease (AD) patients showed significantly in attenuated amyloid plaque deposition as well as short- and long-term memory impairment. through its phytochemical gintonin effect via the mediation in promotion of non-amyloidogenic processing(908). In amyloid β peptide induced AD cell model, ginsenoside Rg1, the main chemical constituent of ginseng, improved the memory impairment associated with Alzheimer's disease (AD), through suppressing the signaling transduction pathways and decreasing the inflammation factors(909)(910); increasing cell viability, reducing oxidative damage (including apoptosis), restoring mitochondrial membrane potential(911). According to the join 17-months old male APP/PS1 mice study by University of Michigan and Yunnan University of Traditional Chinese Medicine, total saponin in leaves of Panax notoginseng (LPNS) attenuated reactive oxygen species (ROS) accumulation and cell death in brain cells through activation of Nrf2 (nuclear translocation) and upregulation of downstream antioxidant systems(912).
 Unfortunately, according to the review over 20 databases from the inception to January 2009 and included all randomized clinical trials (RCTs) from Korea Institute of Oriental Medicine, the use of ginseng for treatments of Alzheimer's disease is scarce and inconclusive(913).

2.2. In Parkinson's and Huntington's diseases
Parkinson's disease is a progressive disorder of the nervous system, affecting movement of muscles(917)(918), speech(919), poster, balance, auto functioning(920), etc. The disease's symptoms worsen over time. According to a multicenter study, phosphorylated forms, pS129 is associated to the severity and progression of  Parkinson diseases(914). NFE2L2 gene, an important regulator of the cellular protection against oxidative stress, if defects can contribute to the pathogenesis of the disease(915)(916). In the pathogenesis of Parkinson's disease (PD), Ginsenoside Rb, effectively inhibited or reversed the aggregation process may represent a viable therapeutic strategy against PD and related disorders, through anti-amyloidogenic and antineurotoxical effects(921). Its water extract in induced cytotoxicity of SH-SY5Y human neuroblastoma cells, also exhibited significant protective effects possibly through the suppression of ROS generation(922). According to Russian Academy of Medical Sciences, use of ginseng and other herbs, such as eleutherococcus, Rhodiola rosea, etc.,  in a complex therapy for Parkinson's disease, may be due to theirs normalized immune, antioxidant, and hormonal parameters(923).
In Huntington's disease, Ginsenosides, the main chemical constituents of ginseng, showed to exert its neuroprotective effect against neurons from glutamate-induced apoptosis in vitro(924).


2.3. In cognitive impairment
Klotho Gene Deficiency has been found to associated to oxidative stress related cognitive impairment(925). In aging mice model, ginseng exhibited anti oxidative stress in ameliorated lipid peroxidation and restores antioxidant capacity(926), and reduced accumulation of intercellular messenger, nitric oxide (NO)(927) may be a potential treatment of herbal medicine for cognitive impairment(927). Ginsenoside Rb1, a major chemical constituent found in ginseng, showed to inhibit cognitive impairment caused by diabetes, through GSK3β, a negative regulator in the hormonal control of glucose homeostasis)-mediated endoplasmic reticulum(ER) stress due to physiological and pathological insults, in high glucose-treated hippocampal neurons(928).

2.4. In neuroprotective effects
In high glucose-induced neurotoxicity in primary cultured rat hippocampal neurons, Ginsenoside Rb1  exerted a wide variety of neuroprotective effects by inhibiting CHOP signaling pathway involved in apoptosis signal in ER stress- and CHOP-mediated apoptosis(940), oxidative stress(926),  mitochondrial dysfunction(929)(941) and neuroinflammation(941). According to University Complutense of Madrid, Ginseng and its major constituents as potential neuroprotective agents against progression of Parkinson's disease(943), may be due to its effectiveness in inhibition of oxidative stress(926) and neuroinflammation(941), decrease of toxins-induced apoptosis(944) and regulation of channels and receptors activity(945)(942).


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Reprinted from Norton Journal, Volume I, Most Common Diseases of Ages of 50 Plus - Chapter of Diseases of Central Nervous system(CNS): Dementia - Treatments in Traditional Chinese Herbal Medicine by Kyle J. Norton  

References
(*) http://www.hindawi.com/journals/ecam/2012/692621/ 
(842) http://www.ncbi.nlm.nih.gov/pubmed/25313575
(843) http://www.ncbi.nlm.nih.gov/pubmed/24224039
(844) http://www.ncbi.nlm.nih.gov/pubmed/23391905
(868) http://www.ncbi.nlm.nih.gov/pubmed/15035888
(869) http://www.ncbi.nlm.nih.gov/pubmed/18635912
(870) http://www.ncbi.nlm.nih.gov/pubmed/25625815
(871) http://www.ncbi.nlm.nih.gov/pubmed/19277659
(872) http://www.ncbi.nlm.nih.gov/pubmed/24979747
(873) http://www.ncbi.nlm.nih.gov/pubmed/23548988
(874) http://www.ncbi.nlm.nih.gov/pubmed/14737017
(875) http://www.ncbi.nlm.nih.gov/pubmed/15215639
(876) http://www.ncbi.nlm.nih.gov/pubmed/25442300
(877) http://www.ncbi.nlm.nih.gov/pubmed/24824453
(878) http://www.ncbi.nlm.nih.gov/pubmed/23147499
(879) http://www.ncbi.nlm.nih.gov/pubmed/19277974
(880) http://www.ncbi.nlm.nih.gov/pubmed/19960983
(881) http://www.ncbi.nlm.nih.gov/pubmed/18198636
(882) http://www.ncbi.nlm.nih.gov/pubmed/12435210
(883) http://www.ncbi.nlm.nih.gov/pubmed/17089329
(884) http://www.ncbi.nlm.nih.gov/pubmed/25063041
(885) http://www.ncbi.nlm.nih.gov/pubmed/20804838
(886) http://www.ncbi.nlm.nih.gov/pubmed/21273053
(887) http://www.ncbi.nlm.nih.gov/pubmed/19632285
(888) http://www.ncbi.nlm.nih.gov/pubmed/25349145
(889) http://www.ncbi.nlm.nih.gov/pubmed/24316034
(890) http://www.ncbi.nlm.nih.gov/pubmed/23717136
(891) http://www.ncbi.nlm.nih.gov/pubmed/6834589
(892) http://www.ncbi.nlm.nih.gov/pubmed/15660764
(893) http://www.ncbi.nlm.nih.gov/pubmed/16782310
(894) http://www.ncbi.nlm.nih.gov/pubmed/23301896
(895) http://www.ncbi.nlm.nih.gov/pubmed/25032018
(896) http://www.tcmassistant.com/herbs/ren-shen.html
(897) http://alternativehealing.org/ren_shen.htm
(898) http://www.ncbi.nlm.nih.gov/pubmed/18083315
(899) http://www.ncbi.nlm.nih.gov/pubmed/24854439
(900) http://www.ncbi.nlm.nih.gov/pubmed/16511867
(901) http://www.ncbi.nlm.nih.gov/pubmed/24503167
(902) http://www.ncbi.nlm.nih.gov/pubmed/23717087
(903) http://www.ncbi.nlm.nih.gov/pubmed/23789219
(904) http://www.ncbi.nlm.nih.gov/pubmed/19519302
(905) http://www.ncbi.nlm.nih.gov/pubmed/8485510
(906) http://www.ncbi.nlm.nih.gov/pubmed/25632113
(907) http://www.ncbi.nlm.nih.gov/pubmed/25568286
(908) http://www.ncbi.nlm.nih.gov/pubmed/22543851
(909) http://www.ncbi.nlm.nih.gov/pubmed/25340298
(910) http://www.ncbi.nlm.nih.gov/pubmed/22214447
(911) http://www.ncbi.nlm.nih.gov/pubmed/24975829
(912) http://www.ncbi.nlm.nih.gov/pubmed/24916704
(913) http://www.ncbi.nlm.nih.gov/pubmed/19584437 
(914) http://www.ncbi.nlm.nih.gov/pubmed/25637461
(915) http://www.ncbi.nlm.nih.gov/pubmed/25496089
(916) http://www.ncbi.nlm.nih.gov/pubmed/20196834
(917) http://www.ncbi.nlm.nih.gov/pubmed/25467144
(918) http://www.ncbi.nlm.nih.gov/pubmed/24933489
(919) http://www.ncbi.nlm.nih.gov/pubmed/25627959
(920) http://www.ncbi.nlm.nih.gov/pubmed/25573070
(921) http://www.ncbi.nlm.nih.gov/pubmed/25449909 
(922) http://www.ncbi.nlm.nih.gov/pubmed/21349320
(923) http://www.ncbi.nlm.nih.gov/pubmed/21165417
(924) http://www.ncbi.nlm.nih.gov/pubmed/19185022 
(925) http://www.ncbi.nlm.nih.gov/pubmed/23084645
(926) http://www.ncbi.nlm.nih.gov/pubmed/25550330
(927) http://www.ncbi.nlm.nih.gov/pubmed/24132508
(928) http://www.ncbi.nlm.nih.gov/pubmed/24535619
(929) http://www.ncbi.nlm.nih.gov/pubmed/24223941
(940) http://www.ncbi.nlm.nih.gov/pubmed/24535619
(941) http://www.ncbi.nlm.nih.gov/pubmed/24132508
(942) http://www.ncbi.nlm.nih.gov/pubmed/25349145
(943) http://www.ncbi.nlm.nih.gov/pubmed/24316034
(944) http://www.ncbi.nlm.nih.gov/pubmed/14637121
(945) http://www.ncbi.nlm.nih.gov/pubmed/24678300

  3. Xi yang shen(946), Yin in nature, the sweet, slightly bitter, cool herb has been used in TCM to treat fatigue(947)(948), diabetes(949), cardiovascular diseases(950)(951) and atopic diseases(952), promote saliva, quench thirst(949)(950), due to yang deficiency of lungs, by enhancing the lung and spleen qi, through increasing the digestive system in absorbing vital energy and reducing the heat causes of qi stagnation through Heart, Lung, Kidney channels.
Phytochemicals
1. Resin
2. Pinene
3. α Phellandrene
4. β Phellandrene
5. α-amyrone,
6. α-amyrinone
7. α-amyrin
8. β-amyrin
8. Viridiflorol
9. Insensole
10. Insensole oxide
11. Ginseng Saponins: ginsenoside -R0, -Rb1, -Rb2, -Rb3, -Rc, -Rd, -Re, -Rf, -Rg1, -Rg2, -Rg3, -Rh1, -RA0, quinquenoside R1, gypenoside X1, F3, F11.
12. Etc.

Herbal xi yang shen used in the treatment and prevention of dementia(953) in traditional Chinese medicine, may be due to its effectiveness of phytochemicals in ameliorated amyloid pathology(953) causes of neuro cells apoptosis(954) and related cognitive deficits(955).

3.1. In Alzheimer's disease
In Alzheimer's disease cell model, induced by Abeta25-35, water extracts of American Ginseng (WEAG), exerted a neuroprotective effects of  SH-SY5, a human derived cell line against cells apoptosi(954). Pseudoginsenoside-F11 (PF11), a main component found in American ginseng, in Alzheimer's disease (AD) mice model, induced by scopolamine, morphine and methamphetamine, significantly mitigated learning and memory impairment in 15 days, through inhibited the expressions of β-amyloid precursor protein (APP) and Aβ1-40 in the cortex and hippocampus, restored the activities of antioxidants in decreased the production of malondialdehyde (MDA), a indicators of lipid peroxidation (953).

3.2.  In Huntington’s disease and Parkinson’s disease
In neurodegeneration-like Huntington's disease and Parkinson's disease rat model, induced by 3-nitropropionic acid (3-NP). preparation of American ginseng leaves and stems significantly reduced brain degeneration through its active phytochemicals, ginsenosides, Rb1, Rb3 and Rd(958), according to Baylor College of Medicine and Austin State University(957). Ginseng saponins, an active ingredients also found in ginseng species, including American ginseng also exerted beneficial effects on aging, central nervous system (CNS) disorders, and neurodegenerative disease through mediated protective mechanisms, including attenuated free radicals(959)(960).

3.3. In Neuroprotective effects
Pseudoginsenoside-F11 (PF11), a phytochemical of Panax quinquefolism (American ginseng) showed to exhibit its neuroprotective effect on methamphetamine (MA)-induced behavioral and neurochemical toxicities in mice(964) and in Parkinson's disease (PD) of rat model, improved locomotor(962) by evoked neuronal excitability was mediated by increased release of glutamate(962); motor balance, coordination, and apomorphine-induced rotation, through inhibiting free radical formation and stimulating endogenous antioxidant release(961). According to the State Key Laboratory of Chinese Medicine and Molecular Pharmacology, water extracts of American Ginseng (WEAG) also exerted its neuroprotective effect on SH-SY5Y cells apoptosis induced by Abeta25-35, in Alzheimer's Disease cellular model(963).

3.4. In  Cognitive impairment 
Amyloid β (Aβ) accumulation, elevated oxidative stress, and apoptosis of the neurons have shown to induce the progression of Alzheimer's disease (AD), Pseudoginsenoside-F11 (PF11) found abundantly in American ginseng, exhibited recognition improvement effect in mouse model, through its antioxidant status in inhibition ofamyloidogenesis and oxidative stress and enhancement of neuronal functions(965) as well as ameliorated cognitive impairment, neuroinflammation, and biochemical alterations caused by accumulation of intercellular messenger, nitric oxide (NO)(966).


Back to General health http://kylejnorton.blogspot.ca/p/general-health.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca

Reprinted from Norton Journal, Volume I, Most Common Diseases of Ages of 50 Plus - Chapter of Diseases of Central Nervous system(CNS): Dementia - Treatments in Traditional Chinese Herbal Medicine by Kyle J. Norton  

References
(*) http://www.hindawi.com/journals/ecam/2012/692621/ 
(842) http://www.ncbi.nlm.nih.gov/pubmed/25313575
(843) http://www.ncbi.nlm.nih.gov/pubmed/24224039
(844) http://www.ncbi.nlm.nih.gov/pubmed/23391905
(946) http://alternativehealing.org/american_ginseng.htm 
(947) http://www.ncbi.nlm.nih.gov/pubmed/19415341
(948) http://www.ncbi.nlm.nih.gov/pubmed/21803872 
(949) http://www.ncbi.nlm.nih.gov/pubmed/24891873 
(950) http://www.ncbi.nlm.nih.gov/pubmed/21985167
(951) http://www.ncbi.nlm.nih.gov/pubmed/15998708
(952) http://www.ncbi.nlm.nih.gov/pubmed/22038929
(953) http://www.ncbi.nlm.nih.gov/pubmed/23541491
(954) http://www.ncbi.nlm.nih.gov/pubmed/19180962
(955) http://www.ncbi.nlm.nih.gov/pubmed/22213250
(956) http://www.ncbi.nlm.nih.gov/pubmed/24132508
(957) https://nwpf.org/stay-informed/news/2005/06/ginseng-compounds-may-fight-huntington%E2%80%99s-disease,-parkinson%E2%80%99s-disease/
(958) http://www.biospace.com/News/ginseng-substances-fight-brain-disease-in-rats/20252020
(959) Plants and phytochemicals for Huntington's disease
(960) http://www.ncbi.nlm.nih.gov/pubmed/16518078
(961) http://www.ncbi.nlm.nih.gov/pubmed/24386001 
(962) http://www.ncbi.nlm.nih.gov/pubmed/21864652 
(963) http://www.ncbi.nlm.nih.gov/pubmed/19180962 
(964) http://www.ncbi.nlm.nih.gov/pubmed/13679222 
(965) http://www.ncbi.nlm.nih.gov/pubmed/23541491 
(966) http://www.ncbi.nlm.nih.gov/pubmed/24132508 

4. 4. Sang shen also known as Mulberry or Morus Fruit, the sweet, sour and cold herb has been used in TCM as antioxidant(968)(969), antiinflammatory(969), anti ageing(991) and neuroprotective(968)(970) agent and to treat vertigo, tinnitus, insomnia, atherosclerosis(971)(973), vascular smooth muscle cells(972), lipid accumulation(974), weak digestion, premature white hair, thirst(967), diabetes(967), diarrhea, etc., as it nourishes Yin, and Blood, promotes generation of Body Fluid, moistens the Intestines, etc. by enhancing the functions of heart, liver and kidney channels(975).

Phytochemicals
1. Resveratrol
2. Anthocyanosides
3. Carotene
4. Thiamine
5. Ribflavin
6. Vtamin C
7. Vannin
8. Linoleic acid
9. Stearic acid
10. Etc.

Herbal sang shen used in the treatment and prevention of dementia(977) in traditional Chinese medicine, may be due to its effectiveness of phytochemicals in exertion of its neuroprotective effects(968)(970) through anti oxidative stress(968)(969), anti inflammatory(969) and anti excitotoxic (involved Alzheimer's disease) mechanisms(978) against cell membrane damage and mitochondrial function induced by oxygen-glucose deprivation (OGD) and glutamate-induced cell death(977).

1. In aging Alzheimer's disease(ADs)
Decreased the levels of serum aspartate aminotransferase caused by oxidative stress(979), alanine aminotransferase(980), triglyceride(981) and total cholesterol(982) due to ageing have shown to involve in the development of Alzheimer's disease. In ageing animals, mulberry extracts (ME), rich in phenolics and anthocyanins, significantly demonstrated  less amyloid beta protein and improved learning and memory ability through its antioxidant enzymes and reduction of oxidative damage(983).
Cyanidin-3-glucoside (C3G) fraction extracted from sang shen effectively protected primary cortical neurons in 7 days, against glutamate-induced cell death cause of dementia, including Alzheimer's disease(ADs(978) in rat model(984).

2. In Parkinson's disease
Parkinson's disease (PD), is one of the most common neurodegenerative disorders with result of dopaminergic deafferentation of the basal ganglia)(985) and involvement of oxidative stress(986)(987).
According to Kyung Hee University, 70 % ethanol extract of mulberry fruit (ME), in dose-dependent manner, in vitro and in vivo PD models showed to prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neuronal damage(999), through its antioxidant and anti-apoptotic effects, regulating reactive oxygen species and NO generation(988).
 
3. Neuroprotective effects
Cyanidin-3-O-beta-d-glucopyranoside (C3G) found abundantly in the mulberry fruits exerted significantly its cytoprotective effect on PC12 cells(derived from a pheochromocytoma of the rat adrenal medulla) under oxidative stress induced neuro-degenerative diseases(983)(989). In neurological disorders, including Alzheimer's and Parkinson's diseases, caused by cerebral ischemia, mulberry leaves (ML) exhibited neuroprotective actions in reduced the cytotoxicity in the PC12 cells against oxygen glucose deprivation with enhanced accumulation of gamma-aminobutyric acid (GABA)(990).

4. In memory improvement
In mice model, mulberry fruits extract, significantly increased pre- and post-synapse formation(992), acetylcholine synthesisation(993), neuronal cell differentiation(994), neurite outgrowth(995) and neuronal cell proliferation(996) in the hippocampus, against loss of memory through its antioxidant in protecting or enhancing neuronal functions mediated by neurotrophic factors, such as nerve growth factor (NGF)(991). According to National Chung Hsing University, in memory deterioration in ageing animals, phenolics and anthocyanins, from mulberry fruits, inhibited amyloid beta protein(998) and improved learning and memory ability through induced  higher antioxidant enzyme activity and less lipid oxidation in both the brain and liver(997).


References
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(842) http://www.ncbi.nlm.nih.gov/pubmed/25313575
(843) http://www.ncbi.nlm.nih.gov/pubmed/24224039
(844) http://www.ncbi.nlm.nih.gov/pubmed/23391905
(967) http://www.ncbi.nlm.nih.gov/pubmed/23936259
(968) http://www.ncbi.nlm.nih.gov/pubmed/25580148
(969) http://www.ncbi.nlm.nih.gov/pubmed/23957352
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(973) http://www.ncbi.nlm.nih.gov/pubmed/21619919
(974) http://www.ncbi.nlm.nih.gov/pubmed/24143244
(975) http://alternativehealing.org/sang_shen.htm
(976) http://www.ncbi.nlm.nih.gov/pubmed/22952555
(977) http://www.ncbi.nlm.nih.gov/pubmed/22359473
(978) http://www.ncbi.nlm.nih.gov/pubmed/23481689
(979) http://www.ncbi.nlm.nih.gov/pubmed/18416873
(980) http://www.researchgate.net/publication/13595646_Increased_aspartate_aminotransferase_activity_in_cerebrospinal_fluid_and_Alzheimer%27s
_disease
(981) http://www.ncbi.nlm.nih.gov/pubmed/25076901
(982) http://www.ncbi.nlm.nih.gov/pubmed/12742802
(983) http://www.ncbi.nlm.nih.gov/pubmed/?term=Morus+Fruit+aging+dementia
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(985) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181806/
(986) http://www.ncbi.nlm.nih.gov/pubmed/24252804
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(995) http://www.ncbi.nlm.nih.gov/pubmed/15010693
(996) http://www.ncbi.nlm.nih.gov/pubmed/22403568
(997) http://www.ncbi.nlm.nih.gov/pubmed/19443193
(998) http://www.ncbi.nlm.nih.gov/pubmed/23451158
(999) http://www.ncbi.nlm.nih.gov/pubmed/22403568  

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