ALZHEIMER’S DISEASE: A CHALLENGE IN MANAGING WITH CERTAIN MEDICINAL PLANTS – A REVIEWHTML Full Text
ALZHEIMER’S DISEASE: A CHALLENGE IN MANAGING WITH CERTAIN MEDICINAL PLANTS - A REVIEW
G. K. Pratap, S. Ashwini and Manjula Shantaram*
Department of Studies in Biochemistry, Mangalore University, Post Graduate Centre, Chikka Aluvara - 571232, Kodagu, Karnataka, India.
ABSTRACT: It is well known that some plants have medicinal properties and their knowledge has been accumulated in the course of many centuries, based on different medicinal systems such as Ayurveda, Unani and Siddha. In India, it is reported that traditional healers use nearly 2,500 plant species and 100 plant species serve as regular sources of medicine for the treatment of various diseases. Alzheimer’s disease is globally recognized as the most common form of dementia and it disrupts critical metabolic processes which keep neurons healthy. These disruptions cause nerve cells in the brain to stop working, lose connections with other nerve cells and finally die. The destruction and death of nerve cell causes the memory failure, personality changes and problems in carrying out daily activities. The Alzheimer’s disease has an abundance of two abnormal structures- amyloid plaques and neurofibrillary tangle. The Alzheimer’s disease is caused by a mixture of genetic, environmental, and life style factors. The current review methodically summarizes the Alzheimer’s disease and the effects of phyto-chemicals of medicinal plants in various models of Alzheimer’s disease.
Alzheimer’s disease, Dementia, Amyloid plaques, Neurofibrillary tangle
INTRODUCTION: Alzheimer’s disease (AD) was the eighth-leading cause of death in 2001. It was discovered in 1906 by Alois Alzheimer, a German neurologist and psychiatrist. However, there was no cure and no effective treatment for it 1. AD is a progressive neurodegenerative disease resulting in the gradual decline of a person’s memory and ability to learn reason, make judgements, communicate, and carry out daily activities 2. AD is an irreversible, progressive brain disease that slowly destroys memory and thinking skills, eventually even the ability to carry out the simplest tasks.
It is a progressive dementia disorder in an elderly population. The pathology includes accumulation of amyloid β-peptide (Aβ), neuro-inflammation and oxidative damage in the brain 3. The nervous system is a complex network of nerve cells, which regulates body’s voluntary and involuntary actions and transmits nerve impulses between different parts of the body.
Research in Alzheimer’s disease has provided the intellectual framework for therapeutic intervention. It proposes that the deposition of β-amyloid is the initial pathological event in AD leading to the formation of senile plaques and then to neurofibrillary tangles, neuronal cell death, and ultimately causes dementia 4. Alzheimer’s disease is globally recognized as the most common form of dementia, with multiple studies projecting that by the year 2050, approximately 115 million people will be affected worldwide 5. The effect of cholesterol in the development of AD apart from mutations in the proteins involved in amyloid-β generation (ßAPP- ß- Amyloid precursor protein, presenilins), the strongest known risk factor influencing the incidence of sporadic AD is the genotype for apolipoprotein E (ApoE), the major carrier of cholesterol in the Central Nervous System (CNS). Individuals carrying one or two copies of the ApoE-e4 allele have a higher risk of developing the disease, compared to those carrying the e3 (the most common) or e2 (which appears to be protective) forms 6.
Methodology: Well-known scientific search engines namely, Google Scholar, PubMed, EMBASE, Mendeley, Science Direct, standard books, Springer Link were used to retrieve online literature. The results are cross-referenced to generate a total number of 95 references cited in this review, during the time span of 1993 - 2016. The current review methodically summarizes the Alzheimer’s disease, effects of phytochemicals of medicinal plants in various models. Table 2 represents the plants, parts used, active compound, mode of extraction and their mode of action in AD therapy. The pictures represent the stages of Alzheimer’s disease and aging of brain (Fig. 1) and the difference between normal brain and Alzheimer’s disease brain (Fig. 2 and 3).The difference between normal neuron and Alzheimer’s disease-infected neuron, also accumulation of beta amyloid precursor protein in neurons is shown in Fig. 4.
Factors Affecting Alzheimer’s disease: While scientists know that Alzheimer’s disease involves the failure of nerve cells, the reason behind this is unknown. However, they have identified certain risk factors that increase the likelihood of developing AD.
Age: The greatest known risk factor for Alzheimer’s disease is increasing age. Most individuals with the illness are 65 years and older. One in nine people in this age group and nearly one-third of the people who are 85 years and older have Alzheimer’s.
Family History: Another risk factor is family history. Research has shown that those who have a parent, brother or a sister with Alzheimer’s are more likely to develop the disease than individuals who do not. The risk increases if more than one family member has the illness 7.
Obesity: It was observed that the obesity at midlife may increase the risk of dementia and AD later in life. Further, the association was weakened by adjustment for other vascular risk factors and diseases, indicating that the effect of obesity on dementia might be partly mediated through these vascular factors. Nevertheless, midlife obesity, high systolic blood pressure and high total cholesterol level were all significant risk factors for dementia, each of them increasing the risk around twice 8.
Researchers have noted a clustering of cardiovascular risk factors, termed syndrome X or the metabolic cardiovascular syndrome. Factors commonly included in this syndrome are hypertension, obesity, dyslipidemia and glucose intolerance. Development of these risk factors is thought to reflect a common underlying pathology. The syndrome leads to an increased risk of diabetes and cardiovascular disease. Both these clinical conditions have been linked to an increased risk of vascular dementia (VaD) and AD 9.
The Alzheimer’s disease can be Caused Due to Mutations in the APP Gene: The apolipoprotein E locus (APOE) on chromosome 19 APOE-e2, APOE-e3 and APOE-e4 is observed. A total of 80% of familial and 64 % of sporadic AD late onset cases have at least one APOE-e4 compared to 31 % of control subjects 10. Autosomal dominant forms of Alzheimer’s disease represented only 5 % of all Alzheimer’s disease cases. Most AD patients have the sporadic form of the disease but for these Alzheimer’s disease cases, genetic susceptibility factors could also increase or decrease the risk of developing the disease 11.
Sex: The overall incidence of Alzheimer’s disease was similar in men and women. Over the age of 90 years the incidence of Alzheimer’s disease was higher for women than men. The risk of vascular dementia was higher for men than women across all age groups. Both studies found that the incidence of dementia and Alzheimer’s disease continued to increase with age up to 85 - 90 years, after which rates increased in women but not in men 12. The prominent rise in incidence rates of dementia in the very old appear due to Alzheimer's disease, while rates for vascular dementia remains moderately constant. These inclinations are particularly marked for minimal dementia, but emphasize the importance of Alzheimer's disease in the community as an origin of cognitive decline of all degrees 13.
Smoking: Smoking had a substantial relationship for increased risk of Alzheimer's disease. Smoking increases cardiovascular risk and nicotine may alter reaction time, learning and memory. Cardio vascular risk factors have been linked to augmented risk of dementia. A previous study found that the fresh smokers were found to be at higher risk of subsequent dementia, Alzheimer's disease, vascular dementia and cognitive decline 14.
Alcohol Consumption: Some studies have shown that heavy alcohol consumption might be associated with an increased risk of dementia in patients with mild cognitive impairment or in men carrying the APOE-e4allele 15. Given the link between VaD, vascular function, and the increasing body of evidence suggesting that AD may be influenced by vascular factors, it may be concluded that this cardiovascular protection decreases incident dementia/cognitive decline. Counter to this are the effects of heavy alcohol consumption and alcoholism as detrimental to memory function 16.
Education: Poor education was cited as a risk factor for Alzheimer’s disease, especially in males. Better education may reveal greater cognitive capacity and reserve, thus postponing the onset of the illness. Similar arguments apply to the size of the head and dementia risk. It is not clear whether it is the learning obtained in childhood or the life-time procurement of knowledge that is protective. Supposing the latter, a trial of cognitive training in individuals at risk of dementia is currently running in the USA 17.
Tau Protein: Tau is one of the microtubules associated with protein that are thought to have a role in the stabilization of neuronal microtubules these in turn provide the track for intracellular transport 18.The molecular mechanisms governing tau aggregation are mainly represented by several post-translational modifications that modify its structure and conformational state.
Hence, abnormal phosphorylation and truncation of tau protein have gained attention as crucial mechanisms that become tau protein in a pathological unit 19. After neuronal damage, tau is released into extracellular space and may be increased in the cerebrospinal fluid (CSF). Elevated CSF levels of tau occur in parenchymal diseases, including neurodegenerative as well as vascular or inflammatory diseases 20.
Oxidative Stress and β-amyloid: Oxidative stress plays a substantial role in the pathogenesis of AD, a damaging disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons (lipids, proteins, and nucleic acids) can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation and β-amyloid peptides. Oxidative stress participates in the development of AD by promoting amyloid -β deposition, tau hyper-phosphorylation and the successive loss of synapses and neurons 21.
The amyloid precursor protein observed in Alzheimer's disease pathology, suggests a time-course of plaque development beginning with neuronal amyloid precursor protein accumulation, then deposition into the extracellular space, subsequent processing by astrocytes or microglia, and resulting in beta-amyloid peptide accumulation in plaques 22.
APP can be proteolyzed directly by α-secretase and then γ-secretase, a process that does not generate amyloid-β, or reinternalized in clathrin -coated pits into another endosomal compartment containing the proteases BACE1 and γ-secretase. The latter results in the production of amyloid-β 23.
Phases of Alzheimer’s disease: Alzheimer’s disease typically progresses slowly in three general stages early, middle, later. Since Alzheimer’s disease affects different way, each person may experience symptoms or progress through the different way 24.
Preclinical Stage: This mild stage, which usually lasts 2 to 4 years, is often when the disease is first diagnosed. In this stage, family and friends may begin to realize that there has been a deterioration in the patient’s cognitive ability. Common symptoms at this stage were included 7. Difficulty holding new information, difficulty with problem solving or decision making. Patients may start to have trouble managing finances or other instrumental activities of daily living which show personality changes. The person may begin to withdraw socially or show lack of motivation and difficulty in conveying thoughts. Further, mislaying belongings or getting lost. The patient may have trouble navigating in familiar surroundings 25.
TABLE 1: DIFFERENT STAGES OF ALZHEIMER’S 26
|Moderate cognitive decline
(Mild or early-stage
|Moderately severe cognitive decline
(Moderate or mid-stage
|Very severe cognitive decline
(Severe or late-stage
Alzheimer’s disease) Dementia
|At this stage
Diminished knowledge of recent events
Reduced ability to perform challenging mental arithmetic
Decreased capacity to perform complex tasks, such as marketing, planning dinner for guests, or paying bills and managing finances
|Major gaps in memory and deficits in cognitive function develop. Some assistance with day-to-day activities becomes necessary. At this stage, individuals may: Become confused about where they are or about the date, day of the week or season.
|This is the ultimate stage of the disease when individuals lose the ability to respond to their environment, then the ability to sit without support, the ability to smile, and the ability to hold their head up. Reflexes become abnormal and muscles grow stiff 27.
Clinical criteria for Mild Cognitive Impairment (MCI): Subjective cognitive complaint, preferably collaborated by an informant objective memory and/or other cognitive impairments that a) are abnormal for the individual’s age and education, as documented using neuropsychological testing b) represent a decline from previous levels of functioning, decline in the normal ability to perform activities of daily living but absence of dementia 28.
FIG. 1: THE STAGES OF ALZHEIMER’S DISEASE AND AGING OF BRAIN
Model of the clinical trajectory of AD. The stage of preclinical AD precedes mild cognitive impairment (MCI) and encompasses the spectrum of pre-symptomatic autosomal dominant mutation carriers, asymptomatic biomarker-positive older individuals at risk for progress into MCI due to AD and AD dementia, as well as biomarker-positive individuals who have demonstrated subtle decline from their own baseline that exceeds the expected in typical aging, but would not yet meet criteria for
MCI. Note that this diagram represents a hypothetical model for the pathological-clinical continuum of AD but does not imply that all individuals with biomarker evidence of AD-pathophysiological process will progress to the clinical phases of the illness 29.
The Alzheimer’s disease is a progressive neuro-degenerative brain disorder it causes a major trouble of normal brain structure and function 31.
FIG. 2: DIFFERENCE BETWEEN NORMAL AND ALZHEIMER’S DISEASE BRAIN 30 Alzheimer’s disease results in shrinkage of brain regions involved in learning and memory which is correlated with major reductions in cellular energy metabolism in living patients. A) Compared with the brain of a healthy person, the brain of an Alzheimer’s disease patients exhibits marked shrinkage of gyri in the temporal lobe (lower part of the brain) and frontal lobes (left part of the brain). B) Positron emission tomography (PET) images showing glucose uptake (red and yellow indicates high levels of glucose uptake) in a living healthy person and a normal conrol subjects. The Alzheimer’s patients exhibits large decrease in energy metabolism in the frontal cortex ( top of brain) and temporal lobes (sides of the brain)
FIG. 3: AD SPREADS THROUGH THE BRAIN 31
Control Measures in Alzheimer’s to lower the Risk of Dementia: 32 The prevention of AD is major public health face, but numerous promising therapies targeting β-amyloid have unsuccessful in late stage clinical trials.
Quit Smoking: Smoking causes a great damage to the body, including the brain. According to studies, daily smokers are at a 45 % higher risk of developing Alzheimer’s in comparison to non-smokers and ex-smokers. Hence, it is strongly advised to quit this detrimental habit 33.
Vitamin B: B Vitamins reduce the levels of a molecule known as homocysteine (HC), which harms the vascular system. When in elevated levels, it increases the risk of strokes, heart diseases, and other vascular problems. Having a higher intake and blood level of Vitamin B12 and folic acid, is associated with a part of the risk of developing Alzheimer’s. Vitamin B6, B12 and folic acid, especially in combination, lower the blood levels of homocysteine, which is a key predictor of risk 34.
Vitamin D: Researchers have found a link between the reduced levels of Vitamin D and cognitive decline, causing dementia symptoms. Therefore, the use of Vitamin D supplements, prevents processes that contribute to dementia and Alzheimer’s 35.
Control of Alcohol Intake: The excessive alcohol use raises the risk of dementia, so it has to be controlled in order to prevent various health issues, including dementia 33. Staying cognitively active throughout life via social engagement or intellectual stimulation is associated with a lower risk of Alzheimer’s disease 36.
Diet: A number of studies suggest that eating certain foods may help keep the brain healthy and
that others can be detrimental to cognitive health. A diet that includes lot of fruits, vegetables and whole grains and is low in fat and added sugar can reduce the risk of many chronic diseases, including heart disease and type 2 diabetes. Researchers are looking at whether a healthy diet also can help preserve cognitive function or reduce the risk of Alzheimer’s 35.
Neuroprotection: Neuroprotection is a broad term to cover any therapeutic strategy to prevent nerve cells called neurons from dying and it usually involves an intervention, either a drug or treatment 36. Neuroprotection is commonly used to refer to any type of therapeutic strategy, usually pharmacological, that can prevent, delay or even reverse neuronal damage, whether it be neuronal death, axonal degeneration or any other form of neuronal injury. Neuroprotective strategies presently being evaluated including acetylcholinesterase inhibitor, glutamate antagonists, calcium channel blockers, nitric oxide synthase inhibitors and so on 37.
Herbal Neuroprotection: Several parts of the herbal plants such as roots, leaves, stems, barks, flowers and fruits are commonly rich in phenolic compounds and other secondary metabolites 5. The pharmacological property of each compound differed in their active principles and many Indian medicinal plant composites are represented as neuroprotective and neuro-pharmacologically active compounds 38.
The herbs or their preparations (or both)are used to treat CNS disorders 39. A few specific herbs and their active ingredients have been identified in particularly Alzheimer’s neuroprotection (Table 2). Antioxidants are not the only active compounds that may stimulate or sedate the nervous system and those that reduce inflammation also help 40.
TABLE 2: PLANTS AND THEIR PHYTOCHEMICALS FOR TREATING ALZHEIMER’S DISEASE
|Α and Β-Asarone||The plant extract shows the neuroprotective
effect against stroke and chemically induced neuro regeneration in rat 41
|Asparagus racemosus Wild||Asparagaceae||Root||Methanolic extract||It prevents ageing, increase longevity, improve mental function and it also used in nervous disorders 41|
|The preventive action against
neurological disorders 42
|The Neuroprotective effect of ethanol
water (1:1) extract of rhizomes of Acoruscalamus against cerebral ischemia 43
|Angelica archangelica (L.)||Apiaceae||Root||Ethanolic extract||It helps inhibited ache activity in-vitro condition 44|
|Aframomummelegueta||Zingiberaceae||Root||Extract of Aframomum, Pmi-006||Neuroprotective effectsin a rat model of traumatic brain injury 45|
|The oxidative stress pathway contributes to Alzheimer’s pathology. As a result, EAF has the potential to be an effective and safe treatment for AD 46|
|Apiaceae or Umbelliferae||Root||Z-Ligustilide, 11-Angeloylsenkyunolide F, Coniferyl Ferulate
and Ferulic acid
|Their ability to inhibit Ab1-40 toxicity On
Dpc-12 cells, showed that they were potent anti-Alzheimer compounds47
|Asparagus racemosus (L.)||Liliaceae||Root||Methanolic
|The plant extract shows the neuroprotection in rats 48|
|Bacopamonniera (L.)||Plantaginaceae||Whole plant||Bacosides||Considered as a possible remedy to coun-teract associated neurological disorders 49|
|Convolvulaceae||Root||Aqueous extract||Scopolamine administration was found to significantly increase the cerebral cortex and load as compared with the control 50|
|Camellia sinensis||Theaceae||Levees||Epicatechin and Epigallocatechin
|These results show the neuroprotective
effects of Cs and its catechins 51
|Celastrus paniculatus Wild||Celastraceae||Whole
|Aqueous extract||The plant extract used to treat physical weakness, mental confusion, alleviate asthma symptoms, reduce headaches, pre-treatment of neuronal cells with Cp seed oil significantly attenuated glutamate-induced neuronal death 41|
|Zingiberaceae||Rhizomes||Aqueous extract||Antidepressant activity is of significant importance in the management of AD 44|
|Petroleum ether||The Curcuma oil ameliorated the ischemia induced neurological functional deficits and the infarct and edema volumes measured after 5 and 24 hrs of ischemia 52|
|Coriandrum sativum ( L.)||Apiaceae||Leaves||Leaf extract||Antioxidant activity 53
|Inhibits amyloid-Β (Aβ) and increased amyloid precursor protein (Aβpp) level in rat 43|
|Apiaceae||Seed||Aqueous seed extract||Therapeutic potential has been established for use in AD patients 54|
|Centella asiatica (L.)||Apiaceae||Leaf||Aqueous extract||The plant extract has been reported to have a comprehensive neuroprotection by different modes of action such as enzyme inhibition and its prevention of amyloid plaque formation in Alzheimer’s disease 55|
|Roots||Powder||The study shows consumption improves the general intelligence rather than STM (short term memory) 56|
|Garcinia indica,||Clusiaceae||Fruit||Methanolic Extract||Exhibited significant neuroprotective potential against 6-ohda, indicating its
anti-Parkinson’s activity in rats 57
|Gastrodia elata||Orchidaceae||Root||Gastrodin||Gastrodinhas protective effects in experimental PD models 58|
|Ginkgo biloba||Ginkgoaceae||Fruit and Seed||Ginkgolide B||Pathophysiology of Alzheimer’s Disease
The mechanism of action of Ginkgo is
believed neuroprotective agent, an antioxidant, a freeradical scavenger, and it help to inhibition beta-amyloid deposition explains its benefit in Alzheimer’s 59
|Limonia acidissima (L.)||Rutaceae||Pulp powder||Soxhlet-extract with methanol||They may prove as neuroprotective against ischemia-reperfusion induced brain injury 60|
|Apocynaceae||Whole plant||Ethanol and Extract||The plant crude extract which indicate that the neuroprotective agent of MJC 61|
|Morusalba (L.)||Moraceae||Leaf||Leaf extract||Mulberry leaf extract provides a viable
treatment for Alzheimer’s disease through the inhibition of amyloid beta-peptide (1e42) fibril formation and attenuation
of amyloid beta-peptide (1e42)-induced neurotoxicity 62
|Mucuna pruriens||Fabaceae||Seeds||Ethanolic extract||The study shows that Mp treatment provides nigrostriatal dopaminergic neuroprotection against pq induced Parkinsonism by the modulation of oxidative stress and apoptotic machinery possibly accounting for the behavioral effects 63|
|Lamiaceae||Leaf||Leaf extract||Improves cognitive function and reduces agitation in patients with mild to moderate Alzheimer's disease 54|
|Ocimum sanctum||Labiatae||Leaf||Alcoholic extract||Can be employed in the treatment of cognitive disorders such as dementia and Alzheimer’s disease 64|
|Piper nigrum (L.)||Piperaceae||Seeds, fruit||Alcoholic and
|Neurodegenerative activity anxiolytic
and antidepressant activity in Alzheimer
rat model 43
|Ginsenoside Rg1||GinsenosideRg1 was observed to have
a neuroprotective effect on dopaminergic neurons through the insulin-like growth factor-I receptor signaling pathway 58
|Ginsenoside Rg1||Neuro protection against the
oxidative stress 58
|Polygonaceae||root||Resveratrol||Diminish superoxide anion; inhibit ROS generation up-regulate the antioxidant
|Ethanolic extract||The ethanol extract of stem bark of
Pongamia Pinnata possesses
activity in albino rats 66
|Fruit||Ethanolic extracts||The present study shows that the fruit possesses an excellent source for natural cognitive enhancer which could be developed in the treatment of AD and other neurodegenerative diseases 67|
|Psidiumguajava (L.)||Myrtaceae||Whole plant and||Ethanolic extracts||To treat inflammation, diabetes and central nervous system depressant activity 68|
|Aqueous extract||The study showed that clove offers neuroprotection against Alcl3-induced neurotoxicity 69|
|Salvia miltiorrhizia bung||Lamiaceae||Leaf and
|Ithelps in protection against cerebral ischemia induced memory impairment in mice model. Extract improved cognitive dysfunction in rats 70|
|Water, methanol, and 95% ethanol extracts||The methanol and water extracts exhibit neuroprotective activities against H2o2-induced toxicity toward Pc12 cells
and are potential candidates for the treatment of H2O2- induced neurodegenerative disease 71
|The potential neuroprotective activity of WCE was shown by reducing histological changes and MDA level in hippocampus 72|
Somnifera (L.) Dunal.
|Solanaceae||Root||The purified extract of the root||The plant mediated inhibition of nitric oxide production, which is known to mediate neurodegeneration during stress73|
|Zingibe rofficinalis||Zingiberaceae||Rhizome||Curcumin||Increasesneurotrophic factors release in the concentration- and time-dependent manners inhibit NFΚbtranslocation and AP-1 activation 74|
FIG. 4: THE DIFFERENCE BETWEEN NORMAL NEURON AND ALZHEIMER’S DISEASE INFECTED NEURON59
Synthetic drugs for Neuroprotection: Neuronal cells are extremely vulnerable and have a limited capacity for self-repair in response to injury. For those reasons, there is obvious interest in limiting neuronal damage. Mechanisms and strategies used in order to protect against neuronal injury, apoptosis, dysfunction, and degeneration in the central nervous system are recognized as neuroprotection. The neuro-protection could be achieved through several classes of natural and synthetic neuroprotective agents (Table 3).
However, considering the side effects of synthetic neuroprotective agents, the search for natural neuroprotective agents has received a great attention 75.
The neurobiological bases of these benefits include the exercise-induced increase in levels of brain-derived neurotrophic factor (BDNF) 76 and other growth factors, stimulation of neuro-genesis, increase in resistance to brain insult 77 and improvement in learning and mental performance 78.
TABLE 3: SYNTHETIC DRUGS OR SUPPLEMENTS USED FOR NEUROPROTECTION
|Name of the drug||Mode of action of drugs|
|Acetyl-L-carnitine||It is hypothesized that the “acetyl” component helps reduce oxidative damage and brain lactate levels 79|
|Acetylcholineesterase inhibitors||This class of drugs functions by inhibiting the neurotransmitter acetyl choline, which can improve brain performance 80|
|L-Theanine||It blocks NMDR receptor when stimulated excessively 81|
|β-Lactam antibiotics||When administered to animals, the β-lactam ceftriaxone increased both brain expression of GLT1 and its biochemical and functional activity. Glutamate transporters are important in preventing glutamate neurotoxicity 82|
|Modafinil||Central nervous system stimulants used for attention deficit disorder, narcolepsy or excessive sleepiness which includes methylphenidate, atomoxetine, modafinil, armodafinil and the amphetamines 83|
|Clomethiazole (GABA agonists)||Neuroprotective agents inhibit reactions in the brain ischemic injury cascade which lead to neuronal death. Gamma-aminobutyric acid (GABA) is a naturally occurring inhibitory neurotransmitter that increases chloride influx into the neuron and counteracts the toxic effects of glutamate81|
|Galantamine hydrobromide||It is a reversible, competitive inhibitor of acetylcholinesterase (AChE), and is the only drug actively marketed for the treatment of AD with proven activity as an allosteric modulator of nicotinic acetylcholine receptors(nAChRs)82|
|NMDA receptor antagonists||Continuous activation of NMDA receptors 84|
|Donepezil,||anti-dementia drugs 85|
|Protein-polymer composite fibers||Peripheral nerve regeneration 86|
|Omega-3 fatty acids||Plays a critical role in the development and function of the|
|central nervous system 87|
|R-flurbiprofen (Flurizan),||reduces beta-amyloid 88|
|Anti-aggregant (NC-758 or Alzhemed)||To prevent the individual fragments from sticking together 87|
|Aß antibody Fab PEG||Alzheimer's disease 89|
|Gantenerumab||Early-stage Alzheimer's disease Phase III 90|
|(amyloid beta-protein inhibitors)|
|CSP-1103||mild cognitive impairment in patients Phase II 91|
|(amyloid beta-protein inhibitor)|
|Propentofylline||In humans it improved cognitive functions as well as global of propen to fylline suggest it may be a promising neuroprotective drug for patients 92|
|Antidepressant-Induced Neurogenesis||New neurons are generated in the adult hippocampus of many species includingrodents, monkeys, and humans 93|
|Interleukin-1 Antagonists||Interleukin-1 (IL-1) is induced immediately after insults to the brain, and elevated|
|levels of IL-1 have been strongly implicated in the neurodegeneration that accompanies stroke, Alzheimer’s disease 94|
|Olesoxime||Olesoxime (Trophos SA’s TRO19622) is a cholesterol-like small molecule withremarkable neuroprotective properties in-vitro, as well as in- vivo. It has demonstratedactivity in four animal models, preventing neurodegeneration and acceleratingneuro-regeneration following neuro-trauma 94|
|Donazepi||Alzheimer's disease 95|
DISCUSSION: The plants used in Indian medicine system are mentioned above in the Table 2. All these plants are used against anti-alzheimer’s, anti-parkinsonism, anti-neuroglia, neuroprotective with memory enhancing property. Some of the phyto-chemical components of these plants are azimine, caepinealkaloids, flavonoids, phenolic compounds, bacosides and nicotine. In recent years, there is a great demand for plant based products because of the broad biological activity. The change in the modern life style and unhealthy food habit have resulted in obesity, diabetes, hyper tension, neurological disorders in a large population. During these conditions, people fully depend on synthetic medicines. However, the long term use of these drugs results in many side effects but natural based products and plant based drugs have no side effects or less side effects.
CONCLUSION: Alzheimer’s disease is the most common cause of dementia, which is becoming more and more frequent in conjunction with growing population. In addition to this, individuals suffering from Alzheimer’s disease is a socio-economic burden in India and other countries which is beyond comparison with any other diseases. Drugs to treat Alzheimer’s disease are very expensive and have side effects. The middle-class family cannot afford to purchase these drugs. But the plant based products are less expensive and without side effects. These drugs may be helpful in enhancing memory in patients. Thus, the knowledge of the medicinal plants helps to develop drugs in modern medicine system.
ACKNOWLEDGEMENT: Authors are grateful to Mangalore University for the support and encouragement.
CONFLICT OF INTEREST: Nil.
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How to cite this article:
Pratap GK, Ashwini S and Shantaram M: Alzheimer’s disease: a challenge in managing with certain medicinal plants - a review. Int J Pharm Sci Res 2017; 8(12): 4960-72.doi: 10.13040/IJPSR.0975-8232.8(12).4960-72.
All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
G. K. Pratap, S. Ashwini and M. Shantaram*
Department of Studies in Biochemistry, Mangalore University, Chikka Aluvara, Karnataka, India.
19 March, 2017
13 October, 2017
12 November, 2017
01 December, 2017