Traditional Chinese Medicines Approach to Preventing and Treating Dementia and Alzheimer’s Disease with Medicinal Herbs

image_pdfimage_print

Dementia refers to a clinical syndrome seen mostly in the elderly and characterized by the impairment of memory and cognition.   The early stages of dementia is called mild cognitive impairment where around 70% progress to dementia at some point.

Dementia is an umbrella term that can manifest into four common types:

  • Alzheimer’s disease (50% to 80% of cases)
  • Vascular dementia (20% to 30% of cases)
  • Lewy body dementia (10% to 25% of cases)
  • Frontotemporal (10% to 15% of cases)

Image result for forms of dementia

Figure 1.  Types of Dementia

Alzheimer’s disease is a progressive neurodegenerative disease and has become the third greatest threat to the elderly, inferior only to cardiovascular disease and cancer.

Pathological hallmarks of Alzheimer’s disease include:

  • increased formation and aggregation of amyloid-beta peptide (Aβ) derived from amyloid precursor protein (APP)
  • formation of intracellular neurofibrillary tangles (NFT)
  • lesions of cholinergic neurons
  • synaptic alterations in cerebral cortex, hippocampus, and other brain regions essential for cognitive function
  • loss of neurons and synapses in the cerebral cortex and certain subcortical regions in the brain

Image result for alzheimer's disease

Figure 2.  Alzheimer’s disease – Healthy Brain and Alzheimer’s disease brain  (Source)

After many years of study, researchers have now accepted that dementia and Alzheimer’s disease are caused by a combination of multiple factors, such as:

  • dysfunctional apoptosis
  • oxidative stress
  • nitrosative stress
  • excitotoxicity
  • disturbance of energy metabolism homeostasis
  • mitochondrial dysfunction
  • inflammatory responses

Research has shown that there is a great deal of evidence indicating that the onset of Alzheimer’s disease is probably the consequences of complex interactions among genetic, environmental, and lifestyle factors.  1  

For over 2,000 years Traditional Chinese Medicine (TCM) has been part of the Chinese health care system.  TCM includes various forms of herbal medicine and hundreds of pharmacological herbal compounds have been identified in TCM for the treatment of many diseases, including:

  • diabetes
  • microbial infections
  • allergies
  • inflammation
  • cardiovascular disease
  • cancer

Many in vitro and in vivo studies have been completed that identify traditionally used medicinal plants and herbs from TCM for neurodegenerative diseases. 

In particular, a number of natural active ingredients from medicinal herbs for the treatment of dementia and Alzheimer’s disease has attracted substantial attention.

These medicinal plants and herbs have both direct and indirect effects on the prevention and treatment of dementia and Alzheimer’s disease.  Some of these mechanisms include, among others:

  • acetylcholinesterase activity
  • antioxidative activity
  • modulation of Amyloid-beta-producing secretase activities
  • amyloid-beta-degradation
  • heavy metal chelating
  • induction of neurotrophic factors
  • cell death mechanisms

Table 1 lists those Chinese herbs that have been used to treat and prevent dementia and Alzheimer’s disease.  Although not an exhaustive and complete list of herbs, these 18 Chinese herbs are the most recognized and studied herbs for the prevention and treatment of dementia and Alzheimer’s disease:

Table 1: Chinese Herbs Used for the Treatment and Prevention of Dementia and Alzheimer's Disease

Latin Botanical NameCommon NameChinese NamePinyin Name
Apium graveolens; Petroselinum crispumApigeninNoneNone
Camellia sinensisGreen tea茶花Cháhuā
Centella asiaticaGotu kola积雪草Ji Xue Cao
Galanthus woronowii.Galanthamine加兰他敏None
Ginkgo bilobaGinko biloba银杏叶Yin Xing Ye
Glycyrrhiza uralensis Fisch Liquiritin; Chinese liquorice甘草Gan Cao; gancao; kan-tsao
Huperzia serrata (Qian Ceng Ta) Huperzine A蛇足石杉she zu shi shan
Polygala tenuifoliaNone遠志Yuan Zhi
Paeonia suffruticosaPoeny牡丹皮Mu dan pi; Cortex Moutan
Panix ginsengGinseng人参Korean ginseng
Panax notoginsengSanchi ginsengtiánqī (田七), sānqī (三七)Tienchi ginseng
Radix puerariae (Pueraria lobata [Willd.] Ohwi) Kudzu; Puerarin葛根Gé gēn
Rhizoma anemarrhenae (Zhimu)Anemarrhena asphodeloides知母Zhi Mu
Rhodiola rosea L.Rhodiola紅景天Hong jing tian
Salvia miltiorrhiza Bunge.Red Sage; Chinese sage丹參Danshen
Salvia officinalisSage鼠尾草None
Scutellaria baicalensisChinese Skullcap; Baical Skullcap黄芩Huáng cen
Uncaria rhynchophylla Cat’s Claw釣鉤藤Gou Teng
Sources: A, B, C, D

Table 2 list those Chinese herbs that have been used to treat and prevent dementia and Alzheimer’s disease along with their medicinal effects and references:

Table 2: Chinese Herbs Used for the Treatment and Prevention of Dementia and Alzheimer's Disease (Medicinal Effects & References)

Latin Botanical NameCommon NameMedicinal EffectsReference
Apium graveolens; Petroselinum crispumApigenin
Apigenin is a potent chelating agent that could decrease the metal ions participating in radical reactions and therefore reduce the creation of free radicalsRef.
Apigenin was reported to protect human neuroblastoma cells SH-SY5Y against apoptosis induced by oxidative stress in vitroRef.
Apigenin was found to improve the memory and learning disorders of aging mice induced by D-galactoseRef.
Camellia sinensisGreen tea
Antioxidant properties of polyphenols, the active components enriched in green tea, may contribute to reducing the risk of dementiaRef.
The in vitro anti-beta-secretase and dual anticholinesterase activities of green tea was reported recently, indicating that tea contains active agents, which may function synergistically, to retard progression of the diseases, assuming that these agents, yet to be identified, reach the brainRef.
Long-term administration of green tea catechins provides effective prophylactic benefits against Abeta-induced cognitive impairment by increasing antioxidative defenses. Haque, A. M., et al. Green tea catechins prevent cognitive deficits caused by Abeta(1-40) in ratsRef.
A higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humansRef.
Co-treated green tea extract (10-50 mug/ml) dose-dependently attenuated Abeta(25-35) (50 muM)-induced cell death, intracellular ROS levels, and 8-oxodG formation, in addition to p53, Bax, and caspase-3 expression, but upregulated Bcl-2. Furthermore, green tea extract prevented the Abeta(25-35)-induced activations of the NF-kappaB and ERK and p38 MAP kinase pathways. Green tea extract may usefully prevent or retard the development and progression of Alzheimer’s diseaseRef.
EGCG inhibited the fibrillization of Abeta in vitro with a half maximal inhibitory concentration of 7.5 mg/L. These studies suggest that EGCG may be a beneficial agent in the prevention of development or progression of ADRef.
Centella asiaticaGotu kola
Used medicinally as anxiolytic agent and as cerebral tonicRef.
Effective in preventing the cognitive deficits, as well as the oxidative stress, caused by intracerebroventricular injection of streptozotocin in ratsRef.
Neuroblastoma cells expressing Aβ identified the ERK/RSK signaling pathway to be involved in a possible molecular mechanism for memory enhancing property of Gotu Kola extractRef.
Selectively decrease hippocampal Aβ levels in AD mouse model expressing the Swedish’ APP and the M146L presenilin 1 mutationsRef.
Galanthus woronowii.Galantamine
Galantamine acts as a selective, reversible, and competitive inhibitor of AchERef.
Galantamine may potentiate memory deficitsRef.
Galantamine has the ability to selectively stimulate or/and modulate neuronal nicotinic acetylcholine receptor, which could facilitate an increase in the synthesis of neurotrophic factors and protect neuronal cells against hazardous effects of oxidative stress and injuryRef.
The combination of galantamine and nicotine works synergistically in inhibiting microglia activationRef.
A clinical trial has confirmed the efficacy and safety of galantamine in the treatment of ADRef.
At six months, patients in the higher dose galantamine group had significantly better scores on the disability assessment for dementia scale than patients in the placebo group (mean treatment effect 3.4 points,). Apolipoprotein E genotype had no effect on the efficacy of galantamine. 80% (525) of patients completed the study. Galantamine is effective and well tolerated in Alzheimer's diseaseRef.
Ginko bilobaGinko biloba
Leaf extract of G biloba (EGb), labeled EGb761, possesses the capacity to treat a variety of neurological disorders, including AD and age-related dementiaRef.
The antioxidant activity of EGb761 may play a substantial role in neuroprotection by decreasing bax/bcl-2 ratiosRef.
EGb761 shows reversal of ischemia-induced reductions of cycloxygenase III mRNA in hippocampal CA1 neurons, inhibition of nitric oxide synthesis, scavenging of free radicals, and attenuation of lipid peroxidationRef.
The effects of oxidative stress were reduced in lymphocytes and brain cells derived of EGb 761-treated AD-transgenic and non-transgenic miceRef.
EGb 761 also affects the production of neurotoxic beta-amyloid peptides (Aβ), for example, by up-regulating α-secretase activity both in cells and animalsRef.
Treatment with EGb761 could partially prevent the indices of oxidative damage in brain from old animalsRef.
One randomized, double-blind, placebo-controlled, and multicenter clinical trial indicated that EGB was safe and capable of stabilizing and improving the cognitive performance and the social functioning of AD patients for 6 months to 1 yearRef.
Pharmacological studies demonstrated that EGb can reverse yohimbine-induced spatial working memory deficit in ratsRef.
EGb761 can improve learning performance in cerebral ischemic miceRef.
EGb761 reduces infarct volume and cell apoptosis in cortex of ischemic miceRef.
EGb761 can reverse memory deficit and decline in choline actyltransferase activities in the hippocampus of rats infused intracerebroventricularly with Aβ1–40Ref.
EGb761 can protect against apoptosis induced by hydroxyl radicalsRef.
EGb761 can protect against cell death induced by beta-amyloidRef.
EGb761 can protect against nitric oxide-induced toxicityRef.
Ginkgolide B were reported to attenuate glutamate-induced neuronal damageRef.
EGb761 can attenuate lipid peroxidationRef.
EGb has potent antioxidant activity and may play a role in the neuroprotective process by attenuating the ischemia/reperfusion-induced oxidative protein modification and lipoperoxidationRef.
Double-blinded randomized controlled clinical trial has demonstrated the efficacy of EGb 761, the standardized preparation of EGb, in treatment for mild to moderate Alzheimer’s diseaseRef.
A 24-week, multicenter, double-blind, placebo-controlled, randomized trial confirmed that EGb 761 improves cognitive function in a clinically relevant manner in patients suffering from dementiaRef.
A randomized placebo-controlled double-blind study showed that EGb 761 (160 mg/d) had a comparable efficacy with donepezil (5 mg/d) in treating mild to moderate AD, and also suggested the efficacy and tolerability of the Ginkgo biloba special extract (Flavogin) in the dementia of the Alzheimer type with special respect to moderately severe stagesRef.
EGb 761 has been suggested to prevent neurodegenerative pathologiesRef.
Glycyrrhiza uralensis Fisch Chinese liquorice
Liquiritin has protective effects on cultured rat hippocampal neuronsRef.
Liquirtin is capable of enhancing the effects of nerve growth factor in extending neuraxonsRef.
Liquirtin can inhibit the activity of acetylcholinesterase and promote the differentiation of neuronal stem cells into cholinergic neuronsRef.
Huperzia serrataHuperzine A
Huperzine A is considered the most potent acetylcholinesterase (AchE) inhibitorRef.
Hup A is also found to be an effective cognition enhancerRef.
Hup A exerts multiple neuroprotective effects, in which the mechanisms may involve the activation of both muscarinic and nicotinic acetylcholine receptors; enhancement of the production of neurotrophic factors; as well as blocking of overstimulated NMDA receptorsRef.
Hup A is effective in improving cognitive impairments in multi-infarct dementia, brain trauma, schizophrenia, and benign senescent forgetfulnessRef.
Hup A neuroprotective effects may be the result of the upregulation of c-jun gene and downregulation of bcl-2 geneRef.
Hup A upregulats nerve growth factor secretion and its downstream signaling; the inhibition of oxidative stress; and the improvement in energy metabolismRef.
Hup A can modulate the processing of amyloid precursor protein (APP) by the regulation of protein kinase CRef.
Hup A can significantly improve the memory of elderly people and AD patients without any notable side effectsRef.
All the advantageous effects of Hup A may be attributed to its potent, reversible, and selective inhibition of AchERef.
Phase IV clinical trials conducted in China have demonstrated that HupA can significantly improve memory of elderly people and patients with AD and VD without any notable side effectsRef.
In the cortex, hippocampus, and striatum of mammalian brain, HupA exerts preferential inhibition against G4 (10S) AChE, which is the physiologically relevant form at cholinergic synapses and is the major form for metabolizing AChRef.
Hup A has been demonstrated by recent studies in our laboratory to protect against H2O2- and β-amyloid (Aβ)-induced cell lesion, decrease the level of lipid peroxidation, increase antioxidant enzyme activities in rat PC12 and NG108–15 cell lines and primary cultured cortical neuronsRef.
Hup A has been demonstrated to protect against serum deprivation-induced toxicityRef.
Hup A has been demonstrated to protect against oxygen-glucose deprivation-induced toxicityRef.
Hup A has been demonstrated to protect against ischemia-induced toxicityRef.
Hup A regulates apoptosis-related genesRef.
Hup A upregulates NGF secretion and its down-stream signalingRef.
Hup A can modulate the processing of amyloid precursor protein (APP) in both rats infused intracerebroventricularly with Aβ1–40 and HEK293sw cell line, via regulating protein kinase C (PKC)Ref.
Polygala tenuifoliaYuan Zhi
An effective compound from the dried root of P tenuifolia, tenuifolin, could inhibit AchE activity or could enhance cholinergic neurotransmissionRef.
Tenuifolin could penetrate the blood–brain barrier and improve cognitive impairment through elevation of the cholinergic system by blocking acetylcholine hydrolysisRef.
A decrease in the secretion of A β 1–40 and A β 1–42 by tenuifolin was reportedRef.
Tenuifolin was found to decrease A β secretion from transfected cells, probably due to inhibition of the beta-site APP cleaving enzymeRef.
A β 25–35-induced cell damage was completely inhibited by Polygala tenuifolia extractRef.
Polygala tenuifolia is classically mentioned as an anti-dementia drug in Chinese and Japanese traditional medicineRef.
It has been shown that Polygala tenuifolia can improve hippocampus-dependent learning and memory, possibly through improvement of synaptic transmission, activation of the MAP kinase cascade, and enhancement BDNF levelsRef.
Polygala tenuifolia up-regulated the expression of BDNF and TrkB mRNA to promote the recovery of the neurons from chronic stress-induced damagesRef.
The methanol fraction of an ethanolic extract from Polygala tenuifolia showed antagonistic action on neurotoxicity induced by glutamate and serum deficiency in PC12 cellsRef.
Paeonia suffruticosaPoeny
Penta-O-galloyl-beta-d-glucopyranose (PGG), a major component of the traditional herb Paenoia suffruticosa, inhibits Aβ fibril formation and destabilizes preformed Aβ fibrils in a concentration dependent matterRef.
Improved long-term memory impairment in an AD mouse model and inhibited Aβ accumulation in brains of treated miceRef.
PGG could protect neuronal cells from oxidative stress by induction of HO-1 gene expressionRef.
Panax ginsengGinseng
Ginsenosides Rb1 and Rg3 exerted significant neuroprotective effects on cultured cortical cells against glutamate-induced neurodegenerationRef.
Protopanaxadiol-type saponins were reported to enhance axonal and dendritic formation activityRef.
Saponins can improve learning and memory in animals impaired with scopolamineRef.
Saponins can improve transient global ischemiaRef.
Saponins can protect brain function and postpone brain aging by decreasing free radicals damage and increasing activities of GSH-Px and SODRef.
The ability of ginsenoside to enhance TrkB expression might also be involved in its protective effectRef.
Panax notoginsengSanchi ginseng
Protective actions against cerebral ischemia, beneficial effects on the cardiovascular system, and haemostatic, antioxidant, hypolipidemic, hepatoprotective, renoprotective, and estrogen-like activities have been describedRef.
Ginsenoside Rg1, a major active component of sanchi ginseng (P. notoginseng), was shown to inhibit β-secretase activity in vitro, to protect PC12 cells against Aβ25–35Ref.
Ginsenoside Rg1 can exert neuroprotective effectsRef.
Ginsenoside Rg3 significantly reduced the levels of Aβ1–40 and Aβ1–42 in SK–N–SH cells transfected with Swedish mutant beta-APPRef.
Radix puerariae (Pueraria lobata [Willd.] Ohwi) Kudzu; Puerarin
Puerarin can protect from learning and memory impairment induced by D-galactoseRef.
Puerarin can protect from β-amyloid peptideRef.
Puerarin can protect from ischemic brain injuryRef.
Puerarin decreases the lipid peroxidase levels and increases superoxide dismutase levels in brain tissuesRef.
Rhizoma anemarrhenae (Zhimu)Zhi Mu
Pharmacological studies demonstrated that Rhizoma anemarrhenae can protect from learning and memory impairment induced by D-galactoseRef.
Rhizoma anemarrhenae can protect from learning and memory impairment induced by β-amyloid peptideRef.
Rhizoma anemarrhenae can enhance memory of normal aged animalsRef.
Rhizoma anemarrhenae is due to its activity of improving the synthetic speed of acetylcholine (ACh) and density of M-type ACh receptorsRef.
Rhizoma anemarrhenae is due to its activity of scavenging free radicalsRef.
Rhizoma anemarrhenae is due to its activity of upregulating brain-derived neurotrophic factor (BDNF)Ref.
Rhodiola rosea L.Rhodiola
Rhodosin can protect from learning and memory impairment induced by D-galactoseRef.
Rhodosin can protect from β-amyloid peptideRef.
Rhodosin can protect from hypoxiaRef.
Rhodosin can protect from cerebral ischemia-reperfusionRef.
Rhodosin can enhance memory of normal-aged ratsRef.
Rhodosin can increase ACh content and reduce cholinesterase activity in the brainRef.
Rhodosin reduces the content of lipid peroxide, and inhibits degeneration of mitochondria in cerebrum cells and hippocampal pyramidal cellsRef.
Salvia miltiorrhiza Bunge.Red sage; danshen
Tanshinone can improve cholinergic functions in central nervous systemRef.
Tanshinone can inhibit inflammatory reaction by inhibiting the expression of pro-inflammatory cytokinesRef.
Tanshinone can inducible nitrogen oxidase (iNOS)Ref.
Salvianolic acid protects from ischemic brain injuryRef.
Tanshinone modulates AChE and NOS protein concentrations in the hippocampus of cranial A β 1–42 injected ratsRef.
Neuroprotective effects of tanshinone was demonstrated in cortical neuronsRef.
Pretreatment of the cells with Tanshinone prior to A β 25–35 exposure suppressed A β -induced cellular events, such as loss in viability, apoptosis, decrease in superoxide dismutase, and glutathione peroxidase activity, increased ROS and decreased mitochondrial membrane potentialRef.
Salvia officinalisSage
Ursolic acid, a pentacyclic triterpenoid carboxylic acid, which can effectively reduce the level of lipid peroxidation and efficiently reverse d-galactose-induced learning and memory impairmentRef.
Extracts of S officinalis are effective in treating mild to moderate ADRef.
Ursolic acid also efficaciously inhibits AchE activity in vitroRef.
Rosmarinic acid, a phenolic derivative of caffeic acid, is also found in water extracts of S officinalis, which exhibits a dose-dependent stalling of the A β fibril formation from A β 1–40 and A β 1–42 as well as A β fibril aggregation, and it can also destabilize the integrity of A β fibrilsRef.
Sage protects PC12 cells from A β 1–42 induced neurotoxicity, which include reactive oxygen species formation, lipid peroxidation, DNA fragmentation, caspase-3 activation, and tau protein hyperphosphorylationRef.
At 4 months, S. officinalis extract produced a significant better outcome on cognitive functions than placeboRef.
Scutellaria baicalensisChinese skullcap
Prevention from myocardial damage induced by ischemia-reperfusion, and improved cerebral ischemiaRef.
Capable of protecting hippocampal neurons against damage induced by injection of Aβ25–35 in hippocampus in ratRef.
Decreases the accumulation of lipid peroxide and proliferation of glial cells induced by Aβ25–35Ref.
Alleviated memory and learning injury and protected morphological change of hippocampal neurons in AD rats induced by Aβ25–35 injectionRef.
Uncaria rhynchophylla Cat's Claw
Our results suggest that Uncaria rhynchophylla has remarkably inhibitory effects on the regulation of Abeta fibrils, and we conclude that this medicinal herb could have the potency to be a novel therapeutic agent to prevent and/or cure AD.Ref.
The active mechanisms were related to blocking of calcium channels, opening of potassium channels, and regulating of nerve transmitters transport and metabolismRef.
Suppression of c-Jun N-terminal kinase (JNK) phosphorylationRef.
U. rhynchophylla significantly inhibited NMDA receptor-activated ion currents in acutely dissociated hippocampal CA1 neurons in cultured brain slicesRef.
In view to AD, U. rhynchophylla intensively inhibited A β aggregation and significantly destabilized preformed A β 1–40 and A β 1–42 fibrilsRef.