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Journal of Neurorestoratology  2019, Vol. 7 Issue (4): 207-222    doi: 10.26599/JNR.2019.9040026
Review Article     
Traditional Chinese medicine-based neurorestorative therapy for Alzheimer’s and Parkinson’s disease
Zhu Zhang1,2, Shiqing Zhang1,2, Cathy Nga-Ping Lui1,2, Peili Zhu1,2, Zhang Zhang1,2, Kaili Lin1,2, Yiwu Dai3,(✉), Ken Kin-Lam Yung1,2,(✉)
1 Department of Biology, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong SAR, China
2 Golden Meditech Center for NeuroRegeneration Sciences (GMCNS), Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong SAR, China
3 Department of Neurosurgery, Bayi Brain Hospital, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, China
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Abstract  

The prevalence of multiple neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), has been dramatically increasing, particularly in the aging population. However, the currently available therapies merely alleviate the symptoms of these diseases and are unable to retard disease progression significantly. Traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years for ameliorating symptoms or interfering with the pathogenesis of aging- associated diseases. Modern pharmacological studies have proved that TCM imparts disease-modifying therapeutic effects against these diseases, such as protection of neurons, clearance of protein aggregates, and regulation of neuroinflammation. This review summarizes the evidence from recent studies on AD and PD therapies regarding the neuroprotective activities and molecular mechanisms of a series of TCM formulations comprising herbs and their active ingredients. The findings of this review support the use of TCM as an alternative source of therapy for the treatment of neurodegenerative diseases.



Key wordstraditional Chinese medicine      Alzheimer’s disease      Parkinson’s disease      neurorestorative therapy     
Received: 21 October 2019      Published: 17 January 2020
Corresponding Authors: Yiwu Dai,Ken Kin-Lam Yung   
Cite this article:

Zhu Zhang, Shiqing Zhang, Cathy Nga-Ping Lui, Peili Zhu, Zhang Zhang, Kaili Lin, Yiwu Dai, Ken Kin-Lam Yung. Traditional Chinese medicine-based neurorestorative therapy for Alzheimer’s and Parkinson’s disease. Journal of Neurorestoratology, 2019, 7: 207-222.

URL:

http://jnr.tsinghuajournals.com/10.26599/JNR.2019.9040026     OR     http://jnr.tsinghuajournals.com/Y2019/V7/I4/207

FormulationsAilment/modelPharmacological functionsTargetReference
Qingxin Kaiqiao FangADReduces pathological degeneration and improves learning and memory functionsBax/Bcl2, caspase-3, p38, and ERK1/2 MAPK[17]
Danggui Buxue TangADProtects amyloid beta (Aβ)-induced cell death of cortical neuronsBax/Bcl2, cleaved-caspases-3 and -9, and PARP[18]
Jia-Jian-Di-Huang- Yin-Zi decoctionPDAttenuates the loss of DA neurons and enhances the survival microenvironmentGDNF, GSH, MDA, GFAP, Iba-1, Tmem119, claudin-5, occludin, CD31(+), MMP2, MMP3, MMP9, CCL2, CCL4, and IL-23[19]
Bushen-Yizhi formulaPDAlleviates motor impairments and DA neuron degeneration andattenuates neuroinflammationTH, Nissl, Iba-1, CD68, GFAP, IL-1β, IL-6, and TNF-α, NLRP3, ASC, caspase-1, and pro-IL-1β[20]
Optimized Yinxieling formulaPDAmeliorates motor dysfunction and suppresses neuroinflammationNO, TNF-α, IL-1β, IL-6, GFAP, Iba-1, and TH[21]
Recipe for nourishing Gan-ShenPDReverses rotenone-induced neuronal death and increases rotenone exposure daysTH[22]
Xiao-Er-An-Shen decoctionPC12 cellsInduces neurite outgrowth and inhibits oxidative stressNF68, NF160, NF200, CREB, and ARE[23]
Modified Kai-Xin-SanPC12 cellsPromotes NGF-induced neuronal differentiationNF68, NF160, NF200, Trk-A, CREB, and ERK1/2[24]
Shaoyao-Gancao TangCell model of tauopathyReduces neuroinflammation-associated tauopathyNO, TNF-α, IL-1β, IL-6, DsRed, ROS, TUBB3, Iba1, LDH, Tau, Bcl2, BH3, caspase-3, caspase-8, and cytochrome c[25]
Kai-Xin-SanAstrocytesIncreases neurotrophic factor synthesisNGF, BDNF, CREB, and ERK1/2[26]
Wu-Tou decoctionMicrogliaInhibits microglial activationTMEM119, TNF-α, and GFP[27]
Table 1The effects of TCM formulations on AD and PD.
Herbs/ingredientsAD modelPharmacological functionsTargetReference
Alpinia oxyphylla
Extracts, Nootkatone, and TectochrysinLPS-/Aβ1–42-induced AD modelAttenuates behavioral cognitive disorder, Aβ accumulation, neuronal degeneration, and neuroinflammationSOD, GSH, GSH-Px, MDA, TChE, Aβ1–42, β-secretase, caspase-3, caspase-8, caspase-9, IKK-α, IκBα, NF-κB, NLRP3, p53, Bad, Bax, Bcl-2, Bcl-xl, Iba-1, IL-1β, IL-6, and p-Tau[28,29,30,31,32]
Radix Notoginseng
Saponins, Rb1, Rg1, and fraction n-butanolCaenorhabditis elegans/SAMP8 mice/ Aβ1-42-injected ratsPrevents cognitive impairment, reduces the generation and increases the degradation of Aβ, rescues neuronal loss, and reverses mitochondrial membrane potential collapse1?42, SOD, GSH-Px, ROS, SKN-1, β-secretase, APP-Thr668, BACE1, ADAM10, IDE, LDH, Bax/Bcl-2, cleaved caspase-3, Cyt C, NMDAR1, CaMKⅡ, ASK-1, JNK, p38, rCBF, and GLT-1[33,34,35,36]
Panax ginseng
Glycoproteins, Rg1, Rh2, Rg5, Rb1, Rg3, polysaccharides, and compound KSAMP1 and SAMP8 mice/SH-SY5Y cell/Wistar rats/ Male ICR miceAmeliorates cognitive function, alleviates Aβ aggregation, prevents neuronal apoptosis, and plays antioxidative and anti-inflammatory rolesCAP1, CAPZB, TOMM40, DSTN, PARP, Bax, Aβ, Tau, Glu, Asp, GABA, Ach, DA, Gly, 5-HT, BDNF, CREB, miR-873-5p, HMOX1, TNF-α, IL-1β, IGF-1, iNOS, COX-2, NO, and NOS[37,38,39]
Royal jelly
Total royal jellyCholesterol-fed rabbitsAmeliorates behavioral deficits, restores autonomic nervous system, attenuates Aβ toxicity, and enhances neuronal metabolic activitiesAβ, AChE, MDA, ChAT, SOD, BACE1, RAGE, LRP-1, TC, LDL-C, IDE, cleaved caspase-3, NAA, Glu, choline, myo- inositol, ROS, and RNS[40, 41]
Rhodiola spp.
Extract1-42-induced AD rat/3xTg-AD mice/ streptozotocin-injected modelAlleviates learning and memory deficits in rat AD models, prevents mitochondrial dysfunction, and protects hippocampal neurons from apoptosisAch, ChAT, SOD, MDA, p-Tau, p-GSK3β, NeuN, TrkB, BDNF, ATP, COX, and caspase-342–44
Ganoderma lucidum
Polysaccharides and alcohol extracts including ganoderic acid and lucidone ASAMP8/APP/PS1 transgenic miceEnhances neurogenesis, alleviates cognitive deficits, improves learning and memory function, and ameliorates neuronal apoptosis and brain atrophyBrdU, NeuN, Ki67, SOX2, EdU, FGFR1, EGFR, ERK, AKT, histone H3, DNMT3A, DNMT3B, Aβ1-42, Nissl, and Tau[45, 46]
Psoralea corylifolia
Prenylated com pounds and total prenylflavonoidsSAMP8 mice/ recombinant AD- related proteinsImproves cognitive performance and inhibits key AD-related protein targets and AD-like neurobiochemical changesBACE-1, GSK-3β, Aβ42, AChE, Tau, TNF-α, IL-6, IL-1β, and d-ROMs[47, 48]
Radix Glycyrrhizae
Extract, licochalcone A and liquiritigeninAβ-GFP 293/SH-SY5Y cells/scopolamine-induced CD-1 miceAmeliorates Aβ-induced aggregation and oxidative stress, promotes neurite outgrowth, and improves scopolamine-induced cognitive impairmentsAβ, ROS, AChE, SOD, IGFBP2, Bad, Bcl2, Bax, cleaved caspase-3, MDA, BDNF, ERK, and CREB[49, 50]
Tripterygium wilfordii
Triptolide and celastrol25–35-induced PC12 cells, APP/PS1 mice/ IMR-32 cellsAmeliorates behavioral and neuropathological changes and attenuates the apoptosis of neuronal PC12 cellsNF-κB, BACE-1, Aβ, CTFβ, MEK1/2, ERK, Raf-1, sAPPα, sAPPβ, FL-APP, CTFα, NEP, IDE, ApoE, NOS2, Iba1, IκBα, Cdc37, ROS, and LC3Ⅱ[51,52,53]
Ginkgo biloba
Extract EGb 761P301S Tau mutant transgenic miceImproves cognitive function, increases autophagic activity and degradation of p-Tau, and shifts microglial proinflammatory activity to anti-inflammatory activityCREB, Tau, Iba-1, S100, p62, LC3Ⅱ/Ⅰ, ATG5, Beclin 1, cleaved caspase-3, p38, and GSK-3β[54]
Table 2The effects of TCMs and their active ingredients on AD.
Herbs/ingredientsPD modelPharmacological functionsTargetReference
Polygonum multiflorum
Extracts, tetrahydroxystilbene glucoside6-OHDA-induced rat and SH-SY5Y cells with MPP+-induced injuryAttenuates motor disorder, suppresses neuroinflammation, protects DA neurons, and resists oxidative stressTH, DA, DOPAC, OX-42, Iba1, NO, TNF-α, IL-1β, ERK1/2, p38, GSH, MDA, ROS, JNK, and caspase-3[55, 56]
Astragalus membranaceus
Astragalosides, polysaccharides, and flavonoidsMPTP-induced mice model andneural stem cellsAlleviates behavioral impairments and DA neuron degeneration, inhibits neuroinflammation, induces neurogenesis, and stabilizes mitochondrial functionTH, Iba1, CD68, SOD, GSH-Px, glutathione, GSSG, NF-κB, NLRP3, ASC, caspase-1, pro- IL-1β, IL-1β, Nrf2, DHE, ROS, DAT, Nurrl, Ptx3, Shh, RN18s, Nestin, Tuj-1, BrdU, Bax, Bcl2, Cyt c, and caspase-3[57,58,59]
Achyranthes bidentata
PolypeptidesSH-SY5Y cells and neuronsexposed torotenone/6-OHDAProtects DA neurons from apoptosisLDH, Bax, and Bcl2[60]
Radix Paeonia Alba
Total glucosidesMPTP-induced miceEnhances DA neuron’s survival and improves motor coordination, striatal dopamine level, and its metabolite levelsDA, DOPAC, HVA, DAT, TH, Bax, Bcl2, α-syn, and CREB[61]
Green tea
(?)-Epigallocatechin-3- gallateMPTP-induced miceRestores impaired movement behavior and modulates peripheral immune responseTH, TNF-α, IL-6, CD3, CD4, and CD8[62]
Acanthopanax senticosus
Root and rhizomeMPTP-induced mouseInhibits mitochondrial dysfunctionOXPHOS, ROS, ATP, MDA, Parkin, PINK1, DJ-1, α-syn, LRRK2, NDUFV2, MT-ND1, SDHA, and SDHC[63]
Ganoderma lucidum
ExtractsMPTP-induced mouseImproves locomotor performance and mitochondrial movement dysfunction and protects against the loss of DA neuronsTH, ROS, ATP, NIX, LC3II/I, AMPK-α, mTOR, ULK1, PINK1, Parkin, Cyt C, caspase-3 and caspase-9[64]
Radix Glycyrrhizae
Isoliquiritigenin and liquiritinTransgenic C. elegans PD model NL5901Inhibits the amyloid formation of α-syn and extends the life span of C. elegans NL5901α-syn[65]
Tripterygium wilfordii
Triptolide and celastrolMN9D cellsInduces autophagy and promotes α-syn clearanceα-syn, p62, and LC3II/I[66]
Table 3The effects of TCMs and their active ingredients on PD.
Herbs/ingredientsCell typePharmacological functionsTargetReference
Rhizoma Acori Tatarinowii
α/β-asarone and oilAstrocytesIncreases both the synthesis and release of NTFs and prevents oxidative stress-induced cell injuryNGF, GDNF, BDNF, CREB, ERK, PKA, ROS, ARE, GCLC, GCLM, NQO1, GST, and AKT[78, 86]
Ginkgo biloba
Extract EGb761Primary rat microgliaReduces neuroinflammatory activationPGE2, 8-iso-PGF, TNF-α, IL-1β, IL-6, COX-1, COX-2, mPGES-1, cPLA2, p38, ERK, JNK, and IκBα[87]
Ganoderma lucidum
PolysaccharidesBV2/ primary mouse microgliaDown-regulates LPS- and Aβ-induced neuroinflammationIL-1β, IL-6, iNOS, TGFβ, Arg1, and MCP-1[88]
Polygonum multiflorum
CRPE56IGIHPrimary mouse microgliaSuppresses LPS-induced neuroinflammatory responsesiNOS, COX-2, HO-1, Nrf2, HO-1, NQO-1, c-Jun, c-Fos, NF-κB, IκBα, ERK, JNK, p38, STAT1, STAT3, NO, PGE2, TNF-α, IL-6, ROS, ARE, AMPK, LKB1, and CaMKII[89]
Psoralea corylifolia
CorylinBV2 microgliaInhibits neuroinflammationby inhibiting the activation of NLRP3 inflammasomeNO, iNOS, COX-2, TNF-α, IL-6, ERK, JNK, p38, IL-1β, NLRP3, ASC, and caspase-1[90]
Royal jelly
Total royal jellyBV2 microgliaSuppresses inflammatory damageiNOS, COX-2, TNF-α, IL-6, HO-1, MCP-1, IL-1β, IκBα, ERK, JNK, and p38[91]
Table 4The effects of TCMs on neuroinflammation.
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