(4th edited )Most common diseases of Elders- Diseases of Central Nervous system(CNS): TCM treatments of Dementia Caused by Spleen 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
B.3.3. Spleen Qi deficiency
Spleen is a vital organ, according to traditional Chinese medicine with function in absorbing nutrients and transport them to body's organs and cells. Spleen Qi deficiency is a condition of the inability of the spleen in maximized transportation of nutrients to body organs, including the brain. Prolong period of malnutrition of brain cells may induce abnormal functions in information transmitting or death of neurons, causing cognitive impairment(844), including learning and memory deficits(842) and changes in brain tissues and behavior patterns(843)(842).

Herbal medicine for Spleen Qi deficiency
1. Peony (Chi Shao)
Chi Shao or Chi Shao Yao with bitter, sour taste and cool in nature is also known as Peony Root, used in TCM as antispasmodic(1000)(1001), anti-inflammatory(1002)(1003), anti allergic(1004)  antibiotic(1005), anticonvulsant(1006), analgesic(1007), anxiolytic(1008) agent and to lower blood pressure(1009), dilate peripheral blood vessels, coronary arteries against heart attack(1010), treat viral hepatitis(1011), chronic constipation(1012), asthma(1013), whooping cough(1014), diabetes(1015)(1016), etc., as it clears heat, cools blood, eliminates blood accumulation, calms paindilates, etc., by enhancing the functions of liver and spleen channels(1017).

Phytochemicals

1. Essential oil

2. Resin

3. Paeoniflorin

4. Paeonol

5. Paeonin

6. Albiflorin

7. Triterpenoids

8. Sistosterol

9. Oxypaeoniflorin

10. Benzoylpaeoniflorin

11. Benzoic acid

12. β sitosterol

13. Gallotannin

14. Pedunculagin

15. 1-O-Galloylpedunculagin

16. Eugeniin

17. Tannin acid

18. Etc.

Herbal shao yao used in the treatment and prevention of dementia(1018)(1019) in traditional Chinese medicine, may be due to its effectiveness of phytochemicals, including major constituent paeoniflorin, in exertion of its neuroprotective effects(1020)(1021) through anti oxidative stress(1022), anti inflammatory(1023), improving neural synapse plasticity(1024) mechanisms, against β-amyloid (Aβ) accumulation(1025) induced  senile dementia and aging-induced cognitive dysfunction(1026).

1.1. Parkinson's disease PD
Strong evidences suggested that peony, possesses wide pharmacological effects in nervous system(1027)(1028). Paeoniflorin, a phytochemical isolated from peony, in PC12 cells induced by 6-OHDA found in patient with Parkinson's disease(1030),showed to suppress mitochondria apoptosis, through its antioxidant capability in increasing glutathione (GSH)(1032). by inhibiting reactive oxygen species (ROS)(1031). In Parkinson's disease (PD) progressive loss of dopaminergic neurons involved movement and mitochondrial dysfunction, in mouse model, peony significantly inhibited mitochondria-mediated apoptosis, via the regulation of expression of immunity, inhibition of cytochrome C associated with the inner membrane of the mitochondrion.release and caspase-3, a protein encoded by in CASP3 gene, activation(1031). According to University of Miami, polyphenols, included baicalin, baicalein, wogonin (in scutellaria), and paeonol, paeonoside, paeoniflori, found in peony, exerted neuroprotective efficacy, probably through improving cerebral blood circulation, involved alleviation of the symptoms of degenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD)(1033).

1.2. In Alzheimer's disease AD
Abeta42 deposition in hippocampus has shown to induce the brain inflammation causes of early onset of Alzheimer's disease AD(1034)(1035). Paeonol(2'-hydroxy-4'-methoxyacetophenone;1-(2-hydroxy-4-methoxyphenyl)ethan-1-one), found in peony, not only protect the nervous system against accumulation of amyloid peptide, Aβ1-42, through its anti-inflammatory and free radical scavenging properties, but also slowed down in regulated  the pathogenic processes associated with AD, through morphological, biochemical and behavioral activities(1036). Aqueous extract of the dry root of Peony in Abeta((1-42))-induced rats, also inhibited Abeta-induced neurotoxicity, through ameliorated cognitive deficit,  cell apoptosis in dose-dependent manner(1037).

1.3. In cognitive impairment
Cognitive impairment is common in patients with the neurodegenerative disease, including Alzheimer's disease (AD) and Parkinson's disease (PD, Paeoniflorin, isolated from the aqueous extract of peony, in rat model, not only showed to promote the cognitive ability, exhibited anti-depressant-like effect and reduced toxicity, but also attenuated the oxidative stress induced Aβ(1-42) by regulating choline acetyltrasferase and the activity of acetylcholine esterase in the hippocampus of Aβ(1-42)(1038)(1039). In Chronic cerebral hypoperfusion, associated with the cognitive deficits of AD, the phytochemical also attenuated cognitive deficit and brain damage through ameliorated astrocytes(star-shaped glial cells in CNS) and microglias(glial cell in CNS) in hippocampus(1040). According to Shanghai Institute of Materia Medica, on cerebral infarction induced neurological symptoms, paeoniflorin (PF) significantly reduced the infarct volume causes of cognitive impairment(1041).

1.4. In learning and memory
Supplementation of paeonol extractedfrom peony, in d-galactose (D-gal)-induced aging mice, significantly improved the learning and memory ability through reduction of oxidative stress, cognitive impairment and neurotoxicity, according to China Pharmaceutical University(1042). Danggui-Shaoyao-San (DSS), an herbal formula,  containing peony and 5 other herbs, used to treat gynecological disorders and neural dysfunctions, in the same model study, showed effectively in improved cognitive ability, through ameliorating oxidative stress induced neuronal apoptosis in the brain(1043). Paeoniflorin, a major constituent of peony, also exhibited its beneficial effect on learning and memory impairment in rodents, by reversed the suppressible effects of adenosine as shown on passive avoidance test and inhibition of long-term potentiation (LTP)(1044).

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  


 2. Bupleurum
Chai Hu  the bitter, slightly cold herb is also known as bupleurum root, used in TCM as antitrypanosomal, antimicrobial and antiviral, such as cold and influenza, alternated chill and fever, malaria(1047), cytotoxic(1045)  and anti-cancer agent(1046) and to treat irregular menses, prolapse of uterus and rectum(1048), etc., as it regulates and clears heat, improve liver function, raises Yang(1048) resolves depression and stagnation, etc. by enhancing the functions of liver, gall bladder, pericardium, triple burner channels.

Phytochemicals
 1. β-terpinene
2. imonene
3. β-fenchene

4. ulegone

5. Isoborneol
6. β-terpineol
7. α-copaene
8. Humulene
9. A-farnesene10. Aromadendrene
11. Cis-caryophyllene
12. β-elemene,13. Gamma-muurolene
14. Patchoulane
15. Pootkatone
16. Ledol
17. Etc.

Herbal chai hu used in the treatment and prevention of dementia(1049)(1050) in traditional Chinese medicine, may be due to its effectiveness of phytochemicals in exertion of its neuroprotective effects(1051) through its cytoprotection of neuron, and the neuroprotective mechanisms (1052), against apoptosis of neurons(1051) due Aβ oligomer-induced neuronal damage(1060) in concentration of corticosterone on hippocampal neurons(1059) in a dose-dependent manner.

Yokukansan, a popular herbal combination in Japan and China, containing chai hu,  may be the next potential herbal formula used for treatment, Alzheimer's disease, Lewy body disease, Parkinson's disease, especially for the behavioral and psychiatric symptoms of dementia (BPSD)(1064)(1065)(1066).

2.1. In dementia symptoms
In dementia, Yokukansan, also known as TJ-54, is composed of sev Angelica acutiloba, Atractylodes lancea, Bupleurum falcatum, Poria cocos, Glycyrrhiza uralensis, Cnidium officinale and Uncaria rhynchophylla,(1052)showed to ameliorated the memory disturbance, anxiety-like behavior, the increase in aggressive behaviors,  the decrease in social behaviors, ameliorates learning deficits and non-cognitive defects(1055) through improvement of neuronal and astroglial cells, via inhibit glutamate-mediated excitotoxicity(1053)(1054). According to ¹Keimei Memorial Hospital in Japan, the formula also showed to improve behavioral and psychological symptoms of dementia (BPSD) together with donepezil in patients with Alzheimer's disease (AD)(1056).

2.2. In Alzheimer's disease and dementia with Lewy bodies
In Alzheimer's disease, Yokukansan improved psychological symptoms of dementia (BPSD)(1058), such as  hallucinations, agitation, anxiety, irritability or abnormal behavior(1057)  in elderly patients with Alzheimer's disease (AD)(1056). In patients with dementia with Lewy bodies Kampo medicine, yokukansan (YKS), including chai hu, also improved behavioural and psychological symptoms of dementia (BPSD), through neuropsychiatric Inventory scores(1061).

2.3. In Parkinson's disease
In neuropsychiatric symptoms in patients with Parkinson's disease, yokukansan, containing Chai hu, using the Unified PD Rating Scale part III (UPDRS-III) and Hoehn and Yahr scale, showed effectively in ameliorated symptoms of delusions, agitation, depression, euphoria, disinhibition with aberrant motor activity tended to improve but irritability showed no change with oral administration of (7.5 g/day) for 12 weeks(1062). In behavioral and psychological symptoms, the herbal formula, also exhibited improvements of these symptoms, without worsening cognitive function, ability to perform activities of daily living, or parkinsonism, after 4 weeks(1063). Yokukansankachimpihange, another formula containing chai hu, showed to exhibit anti hallucinate effects, through its major phytochemical atractylenolide III and β-eudesmol, through its antagonistic activity against serotonin receptors induced non-motor symptom of Parkinson's disease and various forms of dementias(1067).

According to traditional Chinese medicine, the effectiveness of a herbal formula, is not results of single ingredient or single herb, but the combination of all ingredients of all herbs in the formula, even some of herbs in  the formula may show an significant efficacy in Western studies and clinical trials.

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3. Safflower (Hong Hua)
Safflower, is an acrid, warm herb in nature, used in tradition Chinese medicine as anti-bacterial(1070), anti viral(1068)(1069), analgesic(1071), diabetic(1072)(1073), immune stimulant(1074), anti-inflammatory(1071), anti-spasmodic(1075) agent. As  a blood tonic in Chinese medicine, the herb is effective in treating dysmenorrhea(1075), amenorrhea(1075), by breaking up blood stagnation|(1077)(11078), improve blood flow(15) through warm-pungent-liver efficiency network(1079) and regulation of female reproductive hormone(1080) via liver, heart channels(1076).

Phytochemicals
1. Neocarthamin
2. Carthamin
3. Carthamone
4. Carthamidin
5. Saffloryellow
6. Saffloryellow-A
7. Apalmitic acid
8. Myristic acid
9. Lauric acid
10. Etc.

Herbal Safflower (Hong Hua) used in the treatment of symptoms of degenerative diseases(1091) in traditional Chinese medicine, may be due to its effectiveness of phytochemicals, including major constituent Hydroxy-safflor yellow A(1081)baicalin, baicalein, wogonin(1088), in exertion of its neuroprotective effects(1082)(1083), through anti oxidative stress(1086), anti inflammatory(1084))(1085) activities, against β-amyloid (Aβ) accumulation(1081) induced neurotoxicity causes of  Alzheimer's disease.(1087)(1089) and neurodegeneration(1090).

3.1. In Alzheimer's disease
Neuroinflammation has shown to be a major contribution to the development of Alzheimer's disease (AD)(1092). Hydroxy-safflor yellow A (HSYA), isolated from safflower, inhibited Aβ 1-43₁ induced inflammation(1096) through anti microglia-mediated neurotoxicity activity(1094). In PC12 cells induced by β-amyloid neurotoxicity, the phytochemical also inhibited cell viability, glutathione level, through ameliorated enzymes found extensively in body tissues, formation of DNA fragmentation, and levels of reactive oxygen species(1095) and reduced pro-inflammatory mediators(1097).


3.2. In Neuroprotective effects(1098)
In Hydroxy-safflor yellow A (HSYA) at the molecular level, the chemical showed to inhibite energy metabolism disruption, excitatory amino acid toxicity, oxidative stress caused by impaired metabolism in rats with ischemia, through suppressing proinflammatory and upregulating anti-inflammatory mechanism(1099). According to Tianjin Medical University General Hospita, the herb also exerted its neuroprotective effects by inhibiting the accumulation of amyloid-β peptide (Aβ), a major protein component of senile plaques induced neurotoxicity via decreased production of reactive oxygen and nitrogen species(1101), ROS marker, malondialdehyde, and increased the level of glutathione, stabilized mitochondrial membrane(1100) and protected against excitotoxic neuronal death(1102).

3.3. In memory dysfunction
Intake of safflower oil has shown to improve learning and memory ability in n-3 fatty acid deficient male mice(1103) and in an age-related neuro deteriorative mouse model(1106), probably through modulated physiological properties of entorhinal cortex neurons(1104) and the balance of ratio of brain phospholipid(1107), respectively. Nicotiflorin, a natural flavonoid extracted from safflower, in cerebral multi-infarct dementia in rats model, showed to enhance spatial memory through reducd ROS production(1105).


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4. Cinnamon bark (Rou gui)
Rou gui, an acrid, sweet, very hot herb, is also known as Cinnamon bark, used in TCM  as anti-spasmodic(1110), antibiotic(1111), antigastric ulcers(1112), anti impotent and anti diabetic(1113)(1114) agent and to treat hepatitis(1115), flatulence(1116), weak digestion(1116), pain in solar plexus(1110), breast cancer(1117)(1118), tuberculosis(1119)(1120), etc., as it drains the liver heat, eliminates Qi accumulation, disperses nodules, reduces stagnation, etc.by enhancing the functions of heart, lung, bladder channels(1121).

Ingredients
1. Cinnamic aldehyde
2. Cinnamyl acetate
3. Eugenol
4. Aldehyde
5. Pinene
6. Coumarin
7. Cinnamyl alcohol
8. Cinnamic acid
9. Cinnzeylanol
10. Cinnzeylanine
11. Etc.

Cinnamon bark (Rou gui) used in the treatment of symptoms of neurological impairment(1108)(1109) in traditional Chinese medicine, may be due to its effectiveness of phytochemicals, including major constituent cinnamaldehyde (CA) and epicatechin (EC)(1122)  in exertion of its neuroprotective effects(1123)(1123), through anti oxidative stress(1125), anti inflammatory(1124)) activities, against β-amyloid (Aβ) accumulation(1126) induced neurotoxicity causes of  Alzheimer's disease.(1126)(1127) and neurodegeneration(1128).

4.1. In Alzheimer's disease 
Cinnamon, a multifaceted medicinal plant have shown to consist activities against neurological disorders, including Alzheimer's diseases(1129) by blocking and reversing tau modification and aggregation(1131)(1130) and in ischemic stroke induced cell swelling(1130). In β-amyloid polypeptide (Aβ), associated to the development of Alzheimer's disease(AD) and in mouses model, oral administration of cinnamon extract exhibited neuroroprotective effects in enhancing the fully recover of  locomotion defects and totally abolished tetrameric species of Aβ in their brain(1132). In a high fat/high fructose diet induced Alzheimer's disease(AD) symptoms, cinnamon (CN) ameliorated enzyme phosphatase and proteins tensin homolog (PTEN),  tau and amyloid precursor, associated to Alzheimer's disease(AD), through improved insulin sensitivity and related changes in the brain(1133).
According to The Business and Technology Center, West Lafayette, Chinese cinnamon, is one of the tested herb with potential  for prevention and treatment of early onset of Alzheimer's disease(AD)(1134).

4.2. In Parkinson's disease
In a mice model, oral administration of cinnamon (Cinnamonum verum) powder upregulaed and/or maintained the level of Parkin/DJ-1, a beneficial proteins associated to degeneration progression of Parkinson's disease(1135). through protection of dopaminergic neurons(1136). In oligomeriztion of α-synuclein (α-syn) formation associated with the symptoms of Parkinson's Disease, cinnamon extract precipitation (CEppt), inhibited oligomeric and fibrillar forms of α-syn through ameliorated aggregation of β-amyloid polypeptide(1137).

4.3. In neuroprotective effects
Oxidative stress has shown to associate to brain damage due to its high consumption of oxygen.
Cinnamon polyphenols, during oxidative stress, exhibited neuroprotective effects in glial cells by reduced overexpression of the proinflammatory factors(1138) and enhanced prosurvival proteins protein levels (sirtuin 1, 2, and 3, deacetylases) associated to glioma cells survival(1139). Cinnamaldehyde, a major chemical found in cinnamon, inhibited uncontrolled activation of microglia contributes to neuroinflammation involved in the development of neurodegenerative diseases(1140). The herbal water extract, also exerted neuro protective effect against glutamate-induced neuronal death through the inhibition of Ca(2+) influx(1141).

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  

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(1127) http://www.ncbi.nlm.nih.gov/pubmed/20061605
(1128) http://www.ncbi.nlm.nih.gov/pubmed/15229712
(1129) http://www.ncbi.nlm.nih.gov/pubmed/24817901
(1130) http://www.ncbi.nlm.nih.gov/pubmed/20513336
(1131) http://www.ncbi.nlm.nih.gov/pubmed/19433898
(1132) http://www.ncbi.nlm.nih.gov/pubmed/21305046
(1133) http://www.ncbi.nlm.nih.gov/pubmed/24349472 
(1134) http://www.ncbi.nlm.nih.gov/pubmed/17480132 
(1135) http://www.ncbi.nlm.nih.gov/pubmed/24946862
(1136) http://www.ncbi.nlm.nih.gov/pubmed/25284437
(1137) http://www.ncbi.nlm.nih.gov/pubmed/22575665
(1138) http://www.ncbi.nlm.nih.gov/pubmed/24631135
(1139) http://www.ncbi.nlm.nih.gov/pubmed/24239092
(1140) http://www.ncbi.nlm.nih.gov/pubmed/23497886
(1141) http://www.ncbi.nlm.nih.gov/pubmed/10960905