Medicinal Plants Used in Management and Treatment of Alzheimer’s Disease in Africa: An Insight into Therapeutic Avenues and Possible Development as Future Phytopharmaceuticals

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder which needs adequate studies on effective treatment options. The extracts of plants and their effect on the amelioration of AD symptoms have been extensively studied. This review summarizes the use of medicinal plants in treatments and management of Alzheimers disesase, its mechanisms and active primary metabolite responsible for its mode of action and possible future development of this plant extracts into phytopharmaceuticals.The medicinal plants used in management of Alzheimers disease in Africa particularly in Nigeria includes: Yizhi Jiannao , Moringa oleifera (Drumstick tree), Cassia obtisufolia (Sicklepod), Desmodium gangeticum (Sal Leaved Desmodium), Melissa offiffiffi cinalis (Lemon Balm), and Salvia offiffiffi cinalis (Garden sage, common sage). Keywords: Alzheimer’s disease, Antiamyloid aggregation, Antioxidants, Acetyl choline esterase inhibitor, Plant extracts. DOI: 10.7176/JNSR/10-10-04 Publication date: May 31 st 2020

neuronal cells against hydrogen peroxide induced toxicity in part by virtue of their antioxidant and free radical scavenging activities (Katekhaye et al., 2011). Nardostachys jatamansi Nardostachys jatamansi belongs to the family Caprifoliace-ae. It contains sesquiterpene valeranone that has been used for treatment of stress (Lyle et al., 2009). In a study, Nardo-stachys jatamansi exhibited memory retention and learning enhancing abilities in aged and young mice and reversed scopolamine and diazepam induced amnesia. Nardostachys jatamansi also reversed aging induced amnesia (Joshi and Parle, 2006). Karkada et al. (2012) reported efficacy of Nar-dostachys jatamansi in the prevention of stress induced memory deficit.Coriandrum sativum Coriandrum sativum belongs to the family Apiaceae. In one study, Coriandrum sativum was given for 45 days for its ef-ficacy on cognitive function in male Wistar rats. This study was conducted in comparison with aging, scopolamine and diazepam induced amnesia. Coriandrum sativum exhibited memory enhancing effects due to its antioxidant, anti-in-flammatory and cholesterol lowering activities (Vasudevan and Milind, 2009). Ficus carica Ficus carica belongs to the family Moraceae. It was investi-gated for its effect in retrieval, retention and acquisition of spatial recognition. Ficus carica contains quercetin that plays an important role in memory deficit and AD due to its anti-oxidant activity. For this study, mice with memory deficit and normal mice were used. Rectangular maze model and Y-maze were used to assess efficacy of Ficus carica on cognitive func-tions. Hexane extract (100 and 200 mg/kg) was administered to adult swiss Wistar albino mice. In this study, Bacopa monniera and scopolamine were used as standard drug and amnestic agent respectively. Ficus carica 200 mg/kg exhibited maximum nootropic response that is near to response ex-hibited by a standard drug Bacopa monniera. In conclusion, Ficus carica at lower doses exhibits mild memory enhancing effet and higher doses evoke better learning ability and alter behavior (Saxena et al., 2013). Ginkgo biloba Ginkgo biloba belongs to the family Ginkgoaceae. It contains bilobalide that has a neuroprotective activity (Chandrase-karan et al., 2001). Ginkgo biloba decreases free radical and improves memory in patients with AD (Shi et al., 2010). It contains flavonoids that are involved in memory enhance-ment (Bastianetto et al., 2000). Gingko biloba prevents neurodegeneration and GABA inhibitory neurotransmis-sion induced by hippocampal corticosterone (Walesiuk and Braszko, 2009). Administration of Ginkgo biloba significantly improved memory and learning performance in albino rats (Nalini et al., 1992). Ilex paraguariensis Ilex paraguariensis belongs to the family Aquifoliaceae. It has a memory enhancing property. It contains vitamin B12, B1 and C. Ilex paraguariensis is being used as an anti-dementia agent (Bastos et al., 2007). Its memory enhancing property was investigated in different rat models (Colpo et al., 2007).

Africa and use of Medicinal P;ants in Traditional Medicine
The use of medicinal plants as a fundamental component of the African traditional healthcare system is perhaps the oldest and the most assorted of all therapeutic systems. In many parts of rural Africa, traditional healers prescribing medicinal plants are the most easily accessible and affordable health resource available to the local community and at times the only therapy that subsists. Nonetheless, there is still a paucity of updated comprehensive compilation of promising medicinal plants from the African continent. The major focus of the present review is to provide an updated overview of 10 promising medicinal plants from the African biodiversity which have short-as well as long-term potential to be developed as future phytopharmaceuticals to treat and/or manage the neurological disorder alzeheimers disease.
African traditional medicine is the oldest, and perhaps the most assorted, of all therapeutic systems. Africa is considered to be the cradle of mankind with a rich biological and cultural diversity marked by regional differences in healing practices [Aone Mokaila, 2001]. African traditional medicine in its varied forms is holistic involving both the body and the mind. The traditional healer typically diagnoses and treats the psychological basis of an illness before prescribing medicines, particularly medicinal plants to treat the symptoms [Gurib-Fakimet al., 2010]. The sustained interest in traditional medicine in the African healthcare system can be justified by two major reasons. The first one is inadequate access to allopathic medicines and western forms of treatments, whereby the majority of people in Africa cannot afford access to modern medical care either because it is too costly or because there are no medical service providers. Second, there is a lack of effective modern medical treatment for some ailments such as malaria and/or HIV/AIDS, and even neurodegenerative disease, alzeheimers disease which, although global in distribution, disproportionately affect Africa more than other areas in the world.
The most common traditional medicine in common practice across the African continent is the use of medicinal plants. In many parts of Africa, medicinal plants are the most easily accessible health resource available to the community. In addition, they are most often the preferred option for the patients. For most of these people, traditional healers offer information, counseling, and treatment to patients and their families in a personal manner as well as having an understanding of their patient's environment [Gurib-Fakim and Mahomoodally, 2013]. Indeed, Africa is blessed with enormous biodiversity resources and it is estimated to contain between 40 and 45,000 species of plant with a potential for development and out of which 5,000 species are used medicinally. This is not surprising since Africa is located within the tropical and subtropical climate and it is a known fact that plants accumulate important secondary metabolites through evolution as a natural means of surviving in a hostile environment [Manach et al., 20004].The present review aims to explore some medicinal plants in Africa used for treatment of neurodegenerative diseases Alzheimers Disease.

Alzheimers Disease
Alzheimer's disease (AD) is a neurodegenerative disease affecting older adults. In 1906, Alois Alzheimer, a German neuropathologist and psychiatrist discovered AD. About 24 million World population is suffering from dementia, in which majority of patients have AD (Ballard et al., 2011). AD is characterized by memory loss, behavior deterioration, performance impairment, and thought slowness. The condi-tion is mimicked by severe depression (Squire, 1992). Cog-nitive and neural dysfunction occurs due to accumulation of oxidative damage to nucleic acid, protein and mitochondria in the brain. In Spain, survey was conducted on 1,637 people above 64 years of age regarding subjective memory com-plaints (SMC). SMC were reported in 524 persons (32.4%). Cognitive performance, mood, sex, education and age are associated with prevalence of SMC. SMC are reported in 24% of people between 65 and 69 years of age. SMC increase 57% in people up to 90 years or above group. SMC are 52.8% in people with anxiety and depression (Montejo et al., 2011). Severe psychological stress or drug use can cause amnesia. Various allopathic medicines are prescribed in AD but they exert side effects. Therefore, herbal medicine could be a good source of drugs for treatment of AD and memory defi-cit with fewer or no side effects. The present article reviews the medicinal plants that are proven for their efficacy to treat AD and memory deficits. Pathogenesis Two characteristic features are seen in the brain of patients with AD. 1. Senile plaques contain extracellular deposits of amy-loid-beta (Aβ), a peptide synthesized by breakage of Aβ pre-cursors (genetic locus 21q21-22). Abnormal deposits of Aβ are also found in blood vessels.2. Neurofibrillary tangles, dense bundles of abnormal fi-bers in the cytoplasm of neurons which consist of an altered form of the microtubularassociated protein are found in pa-tients with AD (Hoyer, 1992;Iqbal et al., 2005;Kuljis, 2007;Fernandez et al., 2008;Bamburg and Bloom, 2009). Molecular MechanismThe main features of AD are extracellular Aβ pathology and neurofibrillary tau pathology (tangles and threads). For 25 years, most studies have been conducted on the Aβ hypothesis of AD pathogenesis and progression (Pimplikar, 2009). But because of failure in clinical trials of Aβtargeted treatment and the new concept of prion like propagation of intracellular abnormal proteins, tau has come back into the spotlight as a candidate therapeutic target in management of Alzheimer's disease. Tau pathologies are found in a range of neurodegenerative disorders, but extensive analyses of pathological tau in diseased brains has indicated that the abnormal tau protein in each disease is structurally distinct [Downloaded free from http://www.nrronline.org on Friday, April 3, 2020, IP: 197.210.84.30]661Akram and Nawaz. / Neural Regeneration Research. 2017;12(4):660-670. (Avila et al., 2004), supporting the concept that progres-sion of the diverse but characteristic tau pathologies occur through prion like seed dependent aggregation. Therefore, intervention in the conversion of normal tau to abnormal forms and in cell-to-cell transmission of tau may be the key for development of disease modifying treatment of AD and other memory deficits (Hasegawa, 2016).Drug TargetsThe tau and amyloid hypothesis has led to focus on tau and amyloid as treatment targets. The current therapeutic goals are to decrease amyloid levels and prevent amyloid toxicity/aggregation and tau aggregation/phosphorylation. AD has a heterogenous cause with a large percentage termed sporadic AD arising from unknown etiology and a smaller fraction of early onset familial AD caused by mutation in various genes, such as the persenilins (PS1, PS2) and β amyloid precursor protein (APP) (Tang, 2003;Bird, 2008). Other genes such as apolipoprotein E (APOE) are considered to be a risk factor for AD (Kim et al., 2009). Various proteins such as APOE, APP, BACE (Aβ cleaving enzyme), PS1/2, secretases and tau play an important role in the pathogenesis of AD. Therefore, research is focused to develop new inhibitors for PS1, BASE and secretase for treatment of AD. There is also a significant advancement in understanding the cholinesterase function in the brain and the use of cholinesterase inhibitors in management of AD (Wilkinson et al., 2004;Yiannopoulou and Papageorgiou, 2013). The mechanism of new generation of acetyl and butyryl cholinesterase inhibitors is being studied and investigated in clinical trials for AD (Grossberg, 2003). Other strategies, such as hormone therapy, anti-oxidants, cholesterol lowering agents, anti-inflammatory agents and vaccinations are also being investigated for treating AD (La-hiri et al., 2002). Drug Treatment The demonstration of damage to the cholinergic pathways in the brain leads to great interest in drug development. Ace-tylcholinesterase inhibitors are usually prescribed to treat AD. These drugs help in enhancing cognitive functions such as memory and thoughts. These medicines are effective in patients with mild to moderate AD (Houghton and Howes, 2005). Tacrine (a cholinesterase inhibitor) at a high dose (160 mg/d) was reportedly used in the treatment of AD (Schnei-der, 2000). Tacrine was investigated in both clinical trials and neuropsychological test scores, in a 30 week randomized placebo controlled trial (Knapp et al., 1994). However, the use of tacrine is limited due to adverse effects such as hepa-totoxicity (Watkins et al., 1994). Anti-oxidants are effective for AD because they aid in reducing the free radicals that damage the brain cells (Howes and Houghton, 2012). Probiotics have been reported for their efficacy to enhance memory (Lyte, 2011). Probiotics are used as antidepressant in AD. It reduces anxiety like behavior and attenuates psy-chological stress. Neurochemicals are produced by microbes. Immunological and neurological effects are induced by probiotics. Probiotics also have immunomodulating ac-tivity (Misra and Medhi, 2013). In Chinese and Ayurvedic medicines, medicinal plants are used to treat AD, neurode-generative changes and cognitive diseases. Various western medicines being used in memory loss are derived from plants. Plant derived alkaloids such as anticholinesterase have been used to treat AD. In the United Kingdom, plant derived galantamine is also used in the treatment of www.iiste.org ISSN 2224-3186 (Paper) ISSN 2225-0921 (Online) Vol.10, No.10, 2020 24 neuro-degenerative disorders. Five million Americans are suffering from AD and this number will increase up to 7.7 million in 2030. Symptoms of neurodegenerative disorders clearly ap-pear after 60 years of age (Chengxuan et al., 2009). Etiology of neurodegenerative disorders is linked to genetic defect that is 10-15% of total cases. In AD, loss of neurons appears in subcortical structure, cortex and hippocampus. Various compounds have been identified by phytochemical studies such as alkaloids, sterols, triterpenes, polyphenols, tannins, flavonoids and lignins that have pharmacological activities including anti-cholinesterase and anti-amyloidogenic. Medicinal plants are playing a significant role in the management of AD and memory deficit. The important traditional therapeutic methods are Ayurvedic, homeopathy, Unani and Sidha systems of medicine. Unani system of medicine offers traditionally a highly scientific health care therapy as a divine gift and as a result the global interest of the medical profession is focused on medicinal plants. Traditional system of medicine is fundamentally preventive, protective, nutritive and curative. Therefore, traditional medicines are safe and harmless which treat the patients with fewer or no side effects. Herbal medicines have their origins in ancient cultures, including those of the Egyptian, Indians and Chinese. It involves the use of medicinal plants to treat AD and enhances general health and well beings. In fact, many pharmaceutical drugs are based on the synthesized adaptations of naturally occurring compounds found in plants. In recent years, interest in herbal medicine has increased, leading to a greater scientific interest in the medicinal use of plants in treating disease and improving health, often without any significant side effects.

Pathogenesis
Two characteristic features are seen in the brain of patients with AD. 1. Senile plaques contain extracellular deposits of amyloid-beta (Aβ), a peptide synthesized by breakage of Aβ precursors (genetic locus 21q21-22). Abnormal deposits of Aβ are also found in blood vessels. 2. Neurofibrillary tangles, dense bundles of abnormal fibers in the cytoplasm of neurons which consist of an altered form of the microtubular-associated protein are found in patients with AD (Hoyer, 1992;Iqbal et al., 2005;Kuljis, 2007;Fernandez et al., 2008;Bamburg and Bloom, 2009).

Molecular Mechanism
The main features of AD are extracellular Aβ pathology and neurofibrillary tau pathology (tangles and threads). For 25 years, most studies have been conducted on the Aβ hypothesis of AD pathogenesis and progression (Pimplikar, 2009). But because of failure in clinical trials of Aβ-targeted treatment and the new concept of prion like propagation of intracellular abnormal proteins, tau has come back into the spotlight as a candidate therapeutic target in management of Alzheimer's disease. Tau pathologies are found in a range of neurodegenerative disorders, but extensive analyses of pathological tau in diseased brains has indicated that the abnormal tau protein in each disease is structurally distinct (Avila et al., 2004), supporting the concept that progression of the diverse but characteristic tau pathologies occur through prion like seed dependent aggregation. Therefore, intervention in the conversion of normal tau to abnormal forms and in cell-to-cell transmission of tau may be the key for development of disease modifying treatment of AD and other memory deficits (Hasegawa, 2016).

Drug Targets
The tau and amyloid hypothesis has led to focus on tau and amyloid as treatment targets. The current therapeutic goals are to decrease amyloid levels and prevent amyloid toxicity/ aggregation and tau aggregation/phosphorylation. AD has a heterogenous cause with a large percentage termed sporadic AD arising from unknown etiology and a smaller fraction of early onset familial AD caused by mutation in various genes, such as the persenilins (PS1, PS2) and β amyloid precursor protein (APP) (Tang, 2003;Bird, 2008). Other genes such as apolipoprotein E (APOE) are considered to be a risk factor for AD (Kim et al., 2009). Various proteins such as APOE, APP, BACE (Aβ cleaving enzyme), PS1/2, secretases and tau play an important role in the pathogenesis of AD. Therefore, research is focused to develop new inhibitors for PS1, BASE and secretase for treatment of AD. There is also a significant advancement in understanding the cholinesterase function in the brain and the use of cholinesterase inhibitors in management of AD (Wilkinson et al., 2004;Yiannopoulou and Papageorgiou, 2013). The mechanism of new generation of acetyl and butyryl cholinesterase inhibitors is being studied and investigated in clinical trials for AD (Grossberg, 2003). Other strategies, such as hormone therapy, anti-oxidants, cholesterol lowering agents, anti-inflammatory agents and vaccinations are also being investigated for treating AD (Lahiri et al., 2002).

Management of Alzeheimers Diseae 1.6.1. Drug Treatment
The demonstration of damage to the cholinergic pathways in the brain leads to great interest in drug development. Acetylcholinesterase inhibitors are usually prescribed to treat AD. These drugs help in enhancing cognitive functions such as memory and thoughts. These medicines are effective in patients with mild to moderate AD Journal of Natural Sciences Research www.iiste.org ISSN 2224-3186 (Paper) ISSN 2225-0921 (Online) Vol.10, No.10, 2020 25 (Houghton and Howes, 2005). Tacrine (a cholinesterase inhibitor) at a high dose (160 mg/d) was reportedly used in the treatment of AD (Schneider, 2000). Tacrine was investigated in both clinical trials and neuropsychological test scores, in a 30 week randomized placebo controlled trial (Knapp et al., 1994). However, the use of tacrine is limited due to adverse effects such as hepatotoxicity (Watkins et al., 1994). Anti-oxidants are effective for AD because they aid in reducing the free radicals that damage the brain cells (Howes and Houghton, 2012). Probiotics have been reported for their efficacy to enhance memory (Lyte, 2011). Probiotics are used as antidepressant in AD. It reduces anxiety like behavior and attenuates psychological stress. Neurochemicals are produced by microbes. Immunological and neurological effects are induced by probiotics. Probiotics also have immunomodulating activity (Misra and Medhi, 2013). 1.6.2. Treatment using Medicinal Plants 1.6.2.1 Management of Alzheimer's disease Alzheimers disease is a neurodegenerative condition and the most well-known reason for dementia in the old. Despite the fact that the focal point of doctors is the administration of cholinesterase inhibitors in managing AD, it is vital that doctors build up a worldwide administration procedure for their patients. Early and accurate diagnosis of AD helps the patient and physician to manage the disease at onset.

Drug Therapy
This class of medication is presently regarded as the standard treatment of AD. There are four cholinesterase inhibitors which have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of mild to moderate AD. These inhibitors increase the concentration of acetylcholine and the duration of its action in synapses by inhibiting the degradation of acetylcholine. There is also accumulating evidence that cholinesterase inhibitors may improve behavioral and psychological symptoms of AD, such as psychosis and apathy (Cummings, 2000).

Tacrine
Tacrine was the first cholinesterase inhibitors to be endorsed specifically for the symptomatic treatment of patients with mild to moderate AD. The beginning portion for tacrine is 10 mg at 4 times daily, and this dose is increased by 40 mg/day for up to 4 weeks (according to tolerance), to a maximum daily dose of 160 mg (40 mg 4 times daily). Tacrine has been associated with hepatotoxicity (Watkins et al., 1994) and thus requires baseline and multiple follow-up liver enzyme determinations. Tacrine is extensively metabolized by the liver via the cytochrome P450 1A2 isoenzyme system; therefore, it has the potential to interact with other medications metabolized by this isoenzyme, such as theophylline, fluvoxamine, and cimetidine. Tacrine should be avoided in patients with liver disease.

Donepezil
Donepezil was the second cholinesterase inhibitor approved by the FDA for symptomatic treatment of mild to moderate AD in the United States. Donepezil is largely metabolized by the liver, although some of the dose is recovered in the urine as unchanged drug (11-17%) (Dooley et al., 2000). Clinically relevant drug interactions with other drugs have not been extensively studied. Interaction with paroxetine (patient developing increased confusion and agitation) has been reported (Carrier, 1999). Caution should be exercised in using donepezil in patients with severe hepatic or renal disease.

Rivastigmine
This was the third cholinesterase inhibitor approved by the FDA for symptomatic treatment of mild to moderate AD in the United States. Rivastigmine should be titrated every 4 weeks, as opposed to every 2 weeks, as recommended when the drug was first made available. One unique feature of rivastigmine that distinguishes it from other cholinesterase inhibitors is the very low risk of drug interactions in AD patients receiving multiple medications .This is because the metabolism of rivastigmine occurs primarily via enzymatic cleavage (hydrolysis) by cholinesterases at the site of action and does not require the cytochrome P450 enzyme system.

Galantamine
This was the fourth cholinesterase inhibitor approved by the FDA for symptomatic treatment of mild to moderate AD in the United States. Metabolism is hepatic via glucuronidation and the cytochrome P450 isoenzymes; interactions with other drugs that are metabolized through this pathway are therefore possible. Caution should be used in patients with liver disease. The starting dose is 4 mg twice a day, and this dose is increased every 4 weeks. The therapeutic dose is 16-24 mg/day. A 6-month study showed no additional benefit and a higher rate of side effects with a dose of 32 mg/day (Raskind et al., 2000).

Medicinal Plants Used in Treating AD in Africa
Plants provide wealth of bioactive compounds, which exert a substantial strategy for the treatment of neurological disorders such as Alzheimer's disease (Carpinella et al., 2009). In the light of this fact, polyphenolic compounds from vegetables and plants have been exploited because of their potential antioxidative properties ( Ak and Gulcin, 2008). Since there has been growing focus on traditional herbal medicines presently due to the failure of existing treatments, we therefore provide an insight into the therapeutic avenue of medicinal plants used in Africa for Journal of Natural Sciences Research www.iiste.org ISSN 2224-3186 (Paper) ISSN 2225-0921 (Online) Vol.10, No.10, 2020 treatment of Alzheimer's disease.
Moringa Oleifera contains significant antioxidant properties and might be used to protect against neurological disorders. For example, MO leaf extract contains vitamin A (Ferreira et al., 2008) which can prevent oxidative stress through its antioxidant properties and enhance memory through nootropics activities. The extract of MO leaves also contains tannins, saponins, flavonoids, terpenoids and glycosides, which have medicinal properties. These compounds have been shown to be effective antioxidants, anti-carcinogenic agents and anti-inflammatory properties (Ayoola et al., 2008;Davinelli et al.,2015). Since oxidative stress, neuroinflammation, and calcium homeostasis disturbances are components of Alzheimers brains that lead to increased in Aβ production, MO which has agents with multiple antioxidative components could be a possible therapeutic option for this disease.

Tumeric (Curcuma longa)
Turmeric is a sterile plant and does not produce any seeds. The underground rhizomes or roots of the plant are used for medicinal and food preparation. The rhizome is an underground stem that is thick and fleshy ringed with the bases of old leaves. Rhizomes are boiled and then dried and ground to make the distinctive bright yellow spice, turmeric.
A study conducted at UCLA found that curcumin may help the macrophages to clear the amyloid plaques found in Alzheimer's disease. The most prominent characteristic feature in AD is the presence of beta-amyloid plaques. These plaques are basically an accumulation of small fibers called beta amyloid fibrils. Because the deposition of betaamyloid protein is a consistent pathological hallmark of brains affected by AD, the inhibition of A-beta generation, prevention of A-beta fibril formation, destabilization of pre-formed A-beta would be an attractive therapeutic strategy for the treatment of AD. Curcumin has been shown to increase the phagocytosis of amyloidbeta, effectively clearing them from the brains of patients with AD (Fiala et al., 2007).
Macrophages play an important role in the immune system. They help the body to fight against foreign proteins and then effectively clear them. Curcumin was treated with macrophages in blood taken from nine volunteers: six AD patients and three healthy controls. Beta amyloid was then introduced. The AD patients, whose macrophages were treated with curcumin, when compared with patients whose macrophages were not treated with curcumin, showed an improved uptake and ingestion of the plaques. Thus, curcumin may support the immune system to clear the amyloid protein (Zhang et al., 2006).
One of the important pathogenesis in Alzheimer's disease is the chronic inflammation of nerve cells. Several studies have demonstrated the associated inflammatory changes such as microgliosis, astrocytosis and the presence of pro-inflammatory substances that accompany the deposition of amyloid-β (Aβ) peptide. Patients with the prolonged use of certain nonsteroidal anti-inflammatory (NSAID) drugs such as ibuprofen have been shown to have a reduced risk of developing the symptoms of AD; however, the chronic use of NSAID can cause a toxic effect on the kidneys, liver and GI track.
Curcumin has a potent anti-inflammatory effect. Through its various anti-inflammatory effects, it may have a role in the cure of AD caused by oxidation and inflammation (Frautschy and Hu,2001).

Aged Garlic Extract (Allium sativum)
Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidemia, thrombosis, hypertension, dementia, cancer and diabetes (Lawson, 1998). The medicinal use of garlic has a long history. Over the centuries, garlic has acquired a special position in the folklore of many cultures as a formidable prophylactic and therapeutic medicinal agent (Moyer, 1996). Garlic has attracted particular attention of modern medicine because of its widespread use around the world and the cherished belief that it helps to maintain good health by warding off illness and providing more vigor.
The health benefits of garlic as a neuroprotective agent are beginning to emerge (Carmia, 2006). Raw garlic homogenate has been the major preparation of garlic subjected to intensive scientific study, because it is the most Journal of Natural Sciences Research www.iiste.org ISSN 2224-3186 (Paper) ISSN 2225-0921 (Online) Vol.10, No.10, 2020 27 common method of garlic consumption. Raw garlic homogenate is essentially the same as the aqueous garlic extract which has been used in various scientific studies. Allicin (allyl 2-propene thiosulfinate or Diallylthiosulfinate was long thought to be the principal bioactive compound present in aqueous extract or raw garlic homogenate ( Augusti and Mathew, 1975). When garlic is chopped or crushed, allinase enzyme, present in garlic is activated and acts on alliin (present in whole garlic) to produce allicin (Fenwick and Hanley, 1985). Other important sulfur-containing compounds present in garlic homogenate are allyl methyl thiosulfonate, 1-propenyl allylthiosulfonate and -L-glutamyl-S-alkyl-L-cysteine (block, 1985). The enzyme allinase responsible for converting alliin (S-allylcysteine sulfoxide) to allicin is inactivated by heat (Lawson, 1998). Thus the water extract of heat treated garlic contains primarily alliin.
AGE has the potential to protect the brain against neurodegenerative conditions (Brown and Gwebu, 2003) by preventing brain injury following ischemia (Numagami et al., 1996), protecting neuronal cells against apoptosis (Brown and Gwebu, 2003;Mbyirukira and Gwebu, 2003;Kasuga et al., 2001) , and preventing β-amyloid-induced oxidative death (Griffin et al., 1998). Moreover, treatment with AGE or S-allyl cysteine has been shown to prevent the degeneration of the brain's frontal lobe, improve learning and memory retention, and extend lifespan (Nishiyama et al.,1997).

Cattle stick (Carpolobia lutea)
Carpolobia lutea is a perennial shrub native to West and Central Tropical Africa. It is widely distributed in rainforests and the Guinea savannah of Sierra Leone, Cameroon and Nigeria. Extracts and fractions of C. lutea have hitherto only been reported anecdotally to possess benefits to cognition, with the study of C. lutea that has included an examination of its antidiarrheal (Nwidu, Essien et al., 2011), anti-nociceptive (Nwidu,Nwafor et al. 2011) and gastro-protective effects (Nwidu et al.2014).
The presence of secondary metabolites such as polyphenols and flavonoids compounds that include flavones and isoflavones exhibiting scavenging (antioxidant) activities in Carpolobia lutea have been effective in delaying the progression of AD. These antioxidants may counter free radical damage produced during metabolism and for which radical levels may be exacerbated in AD (Parihar and Hemnani 2004;Zhao and Zhao, 2013). A recent in vivo study by Ajiwhen and Bisong (2013) administered a low-dose (1500 mg/kg p.o.) of C. lutea root extract to mice and reported cognitive memory enhancing activity, and this may reflect the potent anti-AChE activity described herein. At this dose of C. lutea roots, no toxicity to mice was reported (Ajiwhen and Bisong 2013).

Lemon Balm (Melissa officinalis)
Melissa officinalis (MO, English: lemonbalm, Lamiaceae), one of the oldest and still most popular aromatic medicinal plants, is used in phytotherapy for the prevention and treatment of nervous disturbances of sleep and gastrointestinal disorders as sedative and antispasmodic medicine. New neuropharmacological investigations showed that ethanol extracts of MO exerted also neuroprotective (Bayat et al.,2012;Kamdem et al., 2013), antioxidant, cyclooxygenase-2 inhibitory (Lin et al., 2012), and antinociceptive activities (Kamdem et al., 2013;Guginski, 2009). Moreover, it is known that MO is used for memory-enhancing effects in European folk medicine (Perry et al., 1996;Perry et al., 1999;Orhan and Aslan,2009).
Indeed, Akhondzadeh et al. (Akhondzadeh et al., 2003) carried out the clinical trial in which MO extract produced a significantly better outcome on cognitive function than placebo in patients with mild to moderate Alzheimer's disease. MO is traditionally used in treating neurological disorders through its anti-AChE (Soodi et al.,2014) and antiagitation properties (Abuhamdah et al., 2008). Moreover, Wake et al. ( Wake et al., 2000) and Kennedy et al. (Kennedy et al., 2003) showed that MO extract has nicotinic receptor activity and that it can displace [3H]-(N)-nicotine from nicotinic receptors in homogenates of human cerebral cortex tissue and they suggested that these mechanisms can explain activity of MO extract in amnesia model. This plant extract is a complex mixture, and its action may be a result of the summation of activities of several components (synergism/additive action of caffeic acid with salvianolic acids, rosmarinic acid, and others). 1.7.6 Garden Sage (Salvia officinalis) Salvia officinalis comes from the Latin word meaning 'to heal' and is widely used in both culinary and medicinal preparations. Many species of Salvia are native to Mediterranean Europe and have been traditionally used for the treatment of a range of problems including digestive and circulation disturbances, bronchitis, coughs, asthma, memory problems, angina, mouth and throat inflammation, depression and excessive sweating. Salvia plants are traditionally noted for their antioxidant effects and ability to enhance 'head and brain' function, improve memory, quicken the senses, and delay age-associated cognitive decline (Perry et al., 1999). Salvia plants are a rich source of polyphenol compounds with over 160 identified polyphenols, comprising an array of phenolic acids and flavonoids. These phenolic compounds include caffeic acid and its derivatives, rosmarinic acid, salvianolic acids, sagecoumarin, lithospermic acids, sagernic acid, and yunnaneic acids. The most prevalent flavonoids include luteolin, apigenin, hispidulin, kaempferol and quercetin (Lu and Foo, 2002). Plants of the genus Salvia are also rich in essential oils, with a large array of terpenoids including a and b-thujone, camphor, 1,8-cineole, a-humulene, b-caryophyllene and viridiflorol. Moreover, they are rich sources of diterpenes and triterpenes such as carnosic acid, ursolic acid, carnosol and tanshinones.