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Aging and disease    2019, Vol. 10 Issue (2) : 307-328     DOI: 10.14336/AD.2018.0328
Review |
Traditional Oriental Medicines and Alzheimer’s Disease
Seong Gak Jeon1, Eun Ji Song1, Dongje Lee1, Junyong Park1, Yunkwon Nam2, Jin-il Kim3,*, Minho Moon1,*
1Department of Biochemistry, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea
2Center for Organic Devices and Advanced Materials, Kyungsung University, Busan 48434, Republic of Korea
3Department of Nursing, College of Nursing, Jeju National University, Jeju-si 63243, Republic of Korea
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Abstract  

Alzheimer’s disease (AD), which is the most major cause of dementia, is a progressive neurodegenerative disease that affects cognitive functions. Even though the prevalence of AD is continuously increasing, few drugs including cholinesterase inhibitors and N-methyl D-aspartate-receptor antagonists were approved to treat AD. Because the clinical trials of AD drugs with single targets, such as β-amyloid and tau, have failed, the development of multi-target drugs that ameliorate many of the symptoms of AD is needed. Thus, recent studies have investigated the effects and underlying mechanisms of herbal formulae consisting of various herb combinations used to treat AD. This review discusses the results of clinical and nonclinical studies of the therapeutic efficacy in AD and underlying mechanisms of the herbal formulae of traditional Oriental medicines and bioactive compounds of medicinal plants.

Keywords Alzheimer’s disease      Oriental herbal medicine      Herbal formulae      Dementia     
Corresponding Authors: Kim Jin-il,Moon Minho   
About author:

These authors contributed equally to this study.

Just Accepted Date: 29 August 2018   Issue Date: 01 April 2019
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Seong Gak Jeon
Eun Ji Song
Dongje Lee
Junyong Park
Yunkwon Nam
Jin-il Kim
Minho Moon
Cite this article:   
Seong Gak Jeon,Eun Ji Song,Dongje Lee, et al. Traditional Oriental Medicines and Alzheimer’s Disease[J]. Aging and disease, 2019, 10(2): 307-328.
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http://www.aginganddisease.org/EN/10.14336/AD.2018.0328     OR     http://www.aginganddisease.org/EN/Y2019/V10/I2/307
CKJSingle herbal ingredientsParts
Yi gan SanUkgansanYokukansanAtractylodes lancea Thunb. DC.rhizome
Wolfiporia extensa Peck Ginns*, #sclerotium
Angelica acutiloba Siebold & Zucc. Kitag.root
Cnidium officinale Makino #rhizome
Uncaria rhynchophylla Miq. Jacks.thorn
Bupleurum falcatum L.root
Glycyrrhiza uralensis Fisch.root

Ba wei di hwang wanPalmijihwanghwanHachimijioganRehmannia glutinosa Lib. var. purpurea Makino**root
Cornus officinalis Sieb. et Zucc.fruit
Dioscorea japonica Thunb.rhizome
Alisma orientale Sam Juzep***, #rhizome
Wolfiporia extensa Peck Ginns*, #sclerotium
Paeonia suffruticosa Andrewscortex
Cinnamomum cassia Blumecortex
Aconitum carmichaeli Debx#root

Jiawei wen dan tangGamiondamtangKamiuntantoPinellia ternata Breit#tuber
Phyllostachys nigra Lodd. Munrostalk
Wolfiporia extensa Peck Ginns*, #sclerotium
Citrus aurantium L.#immature fruit
Citrus unshiu Markov.peel
Glycyrrhiza glabra L.root
Polygala tenuifolia Willd.root
Scrophularia ningpoensis Hemsleyroot
Panax ginseng C. A. Meyerroot
Rehmannia glutinosa Lib.**root
Ziziphus jujuba Millfruit
Ziziphus jujuba Millseed
Zingiber officinale Roscoerhizome

Danggui shaoyao sanDangguijakyaksanTokishakuyakusanAngelica sinensis Oliv. Dielsroot
Paeonia lactiflora Pall.root
Ligusticum chuanxiong Hortrhizome
Wolfiporia extensa Peck Ginns *, #sclerotium
Atractylodes macrocephala Koidz. #rhizome
Alisma orientalis Sam. Juzep ***, #rhizome
Huanglian jiedu tangHwanglyeonhaedok
tang
OrengedokutoCoptis chinensis Franch.rhizome
Scutellaria baicalensis Georgiroot
Phellodendron amurense Rupr.cortex
Gardenia jasminoides Ellisfruit
Table 1  Composition of five herbal formulae for the treatment of AD.
Single herbsBioactive materialsEfficacy and mechanismsRef.
Y G SAtractylodes lanceaAntioxidative effect[54]
β-eudesmolInducing neurite outgrowth via MAPK activation,
Increasing intracellular Ca2+ level induced by PI-PLC activation
[56]
Angelica acutilobaAmeliorating repeated cerebral ischemia-induced memory impairment[57]
Increasing Ach levels and decreasing neuronal apoptosis in the dorsal hippocampus
Alleviating cognitive impairment induced by scopolamine[58]
Uncaria rhynchophyllaInhibiting Aβ aggregation[44]
Suppressing the level of lipid peroxides[59,60]
Improving cognitive function and decreasing AChE activity
Antioxidative effect
[61]
RhynchophyllineProtecting Aβ-induced cytotoxicity via inhibitiion of intracellular Ca2+ overloading
and tau hyperphosphorylation
[62]
Isorhynchophylline
GeissoschizineNon-competitive inhibition against AChE[63]
Uncarinic Acid CA specific inhibitor for the Aβ42 aggregation in nucleation phase[64]
Bupleurum falcatum
Saikosaponin CSuppressing the release of Aβ1-401-42 in various neuronal models
Increasing neurite outghrowth by inhibiting tau hyperphosphorylation
[65]
Glycyrrhiza uralensisAlleviating cognitive impairment induced by Aβ administration[66]
Reducing activity of AChE and catalase in the brain
IsoliquiritigeninInhibiting Aβ aggregation and reducing Aβ toxicity[67]
Cnidium officinaleNo direct reports regarding AD
Wolfiporia extensaNo direct reports regarding AD
Table 2  The efficacy and therapeutic mechanisms of single herbs constituting YGS on AD.
Single herbsBioactive materialsEfficacy and mechanismsRef.
B W D H WRehmannia glutinosaImproving scopolamine-induced cognitive impairment and cholinergic dysfunctions with decreasing TNF-α and IL-1β mRNA expression[75]
Increasing the gene expression of GDNF in astroglial cells via ERK1/2 and cPKC[76]
CatalpolIncreasing ChAT and BDNF levels[73]
Improvement of Aβ-induced memory and learning impariment via reducing Aβ and regulating ROS related enzymes[74]
Cornus officinalis
LoganinImproving scopolamine-induced memory impairment and significantly inhibit AChE activity[77]
p-Coumaric acidInhibiting BACE1 via bind to the β-secretase subsite or to another regulatory site[78]
Gallic acidInhibiting BACE1 activity
Ursolic acid
1,2,3,6-tetra-O-galloyl-β-D-glucoseInhibiting BACE1 via interaction with both the peripheral anionic sites and the catalytic active sites[79]
Tellimagrandin IIInhibiting ChEs via interaction with both the peripheral anionic sites and the catalytic active sites
Dioscorea japonica
Coreajaponin BUpregulating NGF without cell toxicity[80]
Paeonia suffruticosa
1,2,3,4,6-penta-O-galloyl-β-D-glucopyranoseInhibiting the Aβ-aggregation, destabilizing the pre-formed Aβ fibrils
Alleviating long-term memory impairment in Tg2576 mice
[81]
PaeonolImproving the impaired learning behavior induced by Aβ intra-hippocampal injection
Suppressing apoptosis via upregulation of cytochrome oxidase and α-actin
[82]
Cinnamomum cassiaImprovement of cognitive function and glucose homeostasis damaged by Aβ accumulation via enhancing insulin signaling and suppressing TNF-α and iNOS[83]
Alisma orientaleNo direct reports regarding AD
Aconitum carmichaeliNo direct reports regarding AD
Wolfiporia extensaNo direct reports regarding AD
Table 3  The efficacy and therapeutic mechanisms of single herbs constituting BWDHW on AD.
Single herbsBioactive materialsEfficacy and mechanismsRef.
J W W D TPhyllostachys nigraProtecting against neuronal cytotoxicity by Aβ25-35 by decreasing elevated levels of Ca2+,
glutamate release and reactive oxygen species (ROS) generation
[91]
Citrus unshiu
NobiletinProtecting H2O2-induced cytotoxicity via suppression of activation of JNK, p38 and expression of Bax and Caspase 3[92]
Glycyrrhiza glabraEnhancing the spatial memory impairment induced by scopolamine or diazepam via antioxidant and anti-inflammatory activities[93,94]
Reducing AChE activity[96]
2,2',4'-trihydroxychalconeMitigating the memory impairment in the APP-PS1 double transgenic mouse model via reducing the production of Aβ by specific, non-competitive inhibition of BACE1[95]
Polygala tenuifoliaIncreasing axonal length and decreasing number of damaged neurons in Aβ25-35-treated neurons[97]
Improving the scopolamine-induced cognitive decline[98]
Inhibiting AChE activity non-competitive and dose-dependent manner
Protecting the cell death induced by Aβ, C-terminal fragment of APP and glutamate
Scrophularia ningpoensis
HarpagosideImprovement of neurite outgrowth and ChAT (+) neurons reduced by Aβ1-40[99]
Alleviating the cognitive decline and neurodegenerative changes induced by Aβ via increasing BDNF and up-regulating MAPK/PI3K pathway
Panax ginsengPromoting the cognitive function by reducing levels of Aβ1-42 and phosphorylated tau contents via activation of PI3K/Akt signaling pathway[100]
Alleviating cognitive impairment in Tg mAPP mice by decreasing Aβ1-40, Aβ1-42 levels, γ-secretase activity and increasing PKA/CREB signaling pathway[101]
Increased ADAS and MMSE scores in AD patients[102]
Ziziphus jujuba
(fruit)Shakin-ZAntioxidative effect / inhibiting the BChE and AChE[103]
(seed)SpinosinAlleviating AβO-induced cognitive decline / inhibiting the activation of microglia and ChAT[104]
Alleviating the scopolamine-induced memory impairment / increasing phosphorylation of ERK and CREB in the hippocampus[105]
Enhancing cognitive functions via upregulating adult hippocampal neurogenesis and activating ERK/CREB and BDNF pathway[106]
Zingiber officinaleInhibiting the Aβ oligomer formation / dissociating the preformed Aβ oligomer[107]
Increased cell survival, antioxidative activity and decreasing AchE and BChE levels in Aβ-treated rat hippocampal cells
Inhibiting the Aβ-induced LPS and gene expression of TNF-α, IL-1β, COX-2, MIP-1α, MCP-1 and IP-10[108]
Suppressing the AChE activity and lipid peroxidation[109]
Rehmannia glutinosaImproving scopolamine-induced cognitive impairment and cholinergic dysfunctions
with decreasing TNF-α and IL-1β mRNA expression
[75]
Increasing the gene expression of GDNF in astroglial cells via ERK1/2 and cPKC[76]
CatalpolIncreasing ChAT and BDNF levels[73]
Improvement of Aβ-induced memory and learning impariment via reducing Aβ and regulating ROS related enzymes[74]
Citrus aurantiumNo direct reports regarding AD
Pinellia ternataNo direct reports regarding AD
Wolfiporia extensaNo direct reports regarding AD
Table 4  The efficacy and therapeutic mechanisms of single herbs constituting JWWDT on AD.
Single herbsBioactive materialsEfficacy and mechanismsRef.
D S SAngelica SinensisImproving Aβ-induced memory impairment by inhibiting inflammation and the NF-κB[127]
Upregulating GDNF and BDNF in the hippocampus
Inhibiting Aβ-associated neurotoxicity and Aβ aggregation by reducing of oxidative stress[128]
[120]
Neuroprotection to Aβ toxicity and tau phosphorylation through regulating PI3K/Akt/GSK-3β signaling pathway[130]
Decreasing AChE activity[131]
Paeonia lactiflora
PaeoniflorinAttenuating inflammation induced by Aβ1-42 in rodent microglia via inhibiting inflammatory cytokines (TNF-α, IL-1β and IL-6) and chemokines (CXCL1 and CCL-2)[132]
Inhibiting the NF-κB and VEGF/Flt-1 signaling pathways
Mitigating cognitive impairment via regulating SOCS2/IRS-1 in rats with diabetic[133]
Promoting phosphorylation of Akt and GSK-3β
LignansPreventing the Aβ1-42 aggregation via hydrogen or non-hydrogen bond interaction with Aβ1-42[134]
Ligusticum chuanxiong
TetramethylpyrazineInhibiting pro-inflammatory mediators (TNF-α, IL-1β, MCP-1 and ROS) induced by interferon-γ and Aβ25-35[135]
Alisma orientaleNo direct reports regarding AD
Atractylodes macrocephalaNo direct reports regarding AD
Wolfiporia extensaNo direct reports regarding AD
Table 5  The efficacy and therapeutic mechanisms of single herbs constituting DSS on AD.
Single herbsBioactive materialsEfficacy and mechanismsRef.
H L J D TCoptis chinensis
CoptisineSuppressing IDO expression via reducing Aβ formation[150, 152]
Inhibiting AChE and BChE activity[154]
BerberineInhibiting AChE and BChE activity[154]
Palmatine
Jatrorrhizine
GroenlandicineInhibiting AChE, BChE and BACE1 activity
Epiberberin
Scutellaria baicalensis
BaicaleinImproving AD-like pathology together with improved cognitive performance by activation of the GABA type A receptors and the α-secretase processing of APP.[155]
Alleviating spatial learning and memory deficits induced by gamma-ray radiation.[156]
Stimulating neurogenesis and up-regulating BDNF-pCREB pathway
WogoninImproving impaired cognitive function in 3xTg AD mcie[157]
Reducing β-secretase levels, Aβ aggregation and phosphorylated tau
Protecting against apoptosis and mitochondrial membrane potential elevation via suppression of the cleaved PARP and expression of Bax
Phellodendron amurenseProtecting Aβ-induced neurotoxicity via upregulating Bcl-2/Bax ratio and down-regulating cytochrome c and caspase-3 expression[158]
Gardenia jasminoidesReducing Aβ-induced cytotoxicity via reduction of oxidative stress[159]
6'-O-trans-p-coumaroylgeniposideEnhancing short-term memory in Aβ transgenic drosophila model[160]
6'-O-acetylgeniposide
GeniposideInhibiting the activity of AChE and increasing the activity of ChAT[161]
Mitigating the cognitive impairment in APP/PS1 mice by inhibition of Aβ1-42-induced cholinergic deficit and amyloidosis via inhibition of MAPK
Table 6  The efficacy and therapeutic mechanisms of single herbs constituting HLJDT on AD.
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