Alzheimer’s disease (AD) is attributed to the inception of amyloid plaques and tangled fibers which consequently results in neurodegeneration featured by impairment of cognitive function and amnesia (memory loss) (Anand et al., 2014; Sahebkar et al., 2021). AD manifests the highest prevalence in the elderly and is adjudged as predominant neurodegenerative disorders, ostensive with limited and inefficacious treatment regimes. Discerning the pathophysiology expounds the significant hallmarks of AD and assists in diagnosis wherein a patient is screened for one or more of the following characteristics: amnesia (memory loss), aphasia (expressive aphasia is an inability to find right words while receptive aphasia demonstrates an inability to understand), apraxia (loss of motor function) and agnosia (loss of functioning of 5 senses) (Sahebkar et al., 2021). The FDA (Food and Drug Association) approved drugs for the treatment of AD includes the administration of AChEIs (acetylcholinesterases inhibitors), NMDA (N-methyl-D-aspartate receptor antagonists) (Auld et al., 2002; Anand et al., 2014), Selegiline (used in the treatment of Parkinson’s Disorder) (Anand et al., 2014; Abeysinghe et al., 2020), estrogen therapy (Auld et al., 2002), NSAIDs (Non-Steroids Anti-Inflammatory Drugs) (Abeysinghe et al., 2020). A comprehensive overview of these drugs is listed in Table 1. Addressing Alzheimer’s is not limited to timely diagnosis and implementation of constructive treatment plans. The preponderance of AD in the elderly is often misleading as the symptoms are misread for aging. The classification of different stages of the disease progression of AD is depicted in Figure 1. Proper intervention in accordance with diseases progression ameliorates disease management. The irreversible damage to the brain cells and involuted pathophysiological, events associated with AD have always emphasized the need for the development of novel drugs and therapeutics, which render better outcomes with fewer or no side effects.

The plethora of bioactive phytocompounds, useful vitamins and chemicals has maximized the need to derive their therapeutic potentials (Garriga et al., 2015). Their feasibility to be taken as a dietary supplement, unparallel chemical diversity, remarkable efficacy, and their dexterity to interact with biological targets to positively revamp biological functions is superlative (Mir and Albaradie, 2014; Yuan et al., 2016). The presence of alkaloids, flavonoids, carotenoids, and other phytonutrients in natural products is the underpinning for nutraceuticals, which believes that diet has an undeniable effect on epigenetics (Mir and Agrewala, 2008; Mir, 2015). Moreover, the consumption of functional foods which enhances brain functioning (often termed as brain foods) will aid in overall management of AD (Mir and Albaradie, 2015; Bhat et al., 2022). Though the current research is oriented toward food-based novel drugs, it is fundamental to develop pharmacological preparations to address AD. The principle of nutraceuticals emphasizes developing interventions that are beyond the diet and healthy eating and shouldn’t be misapprehended for devising a diet plan rich with supplements as this can only compensate the nutritional requirements and is ineffective to combat a malady. Significant pharmacological properties like neuroprotective, anti-oxidant, anti-inflammatory, anti-apoptotic, etc., demonstrated by phytonutrients like tannins, alkaloids, phenols, carotenoids can be inspected to devise potential drugs (Mir et al., 2019; Lautie et al., 2020; Qadri et al., 2021). In this review, we will constructively look into important hallmarks of AD, neuroprotective and anti-Alzheimer’s properties exhibited by phytonutrients and explore their food sources.

The prominent hallmarks of AD are hypothesized to be the production of Aβ plaques and the neurofibrillary tangles (NFTs) in different regions of patients. Further, AD is grossly progressed by aberrant phosphorylation and agglomeration of neurofibrillary tau proteins (Majeed et al., 2021), causing instability of microtubules and concomitantly includes functional abnormalities in the axon transportation (Atlante et al., 2020).

Subsequently the cognitive impairment and neurodegeneration is currently thought to be a primary driver for NFTs (Dey et al., 2017). These occurrences suggest a link between aberrant tau proteins and memory deficits in Alzheimer’s patients associated with various AD associated hallmarks and recognized potential therapeutic targets (Figure 2). Originally, it was presumed that Aβ peptide accumulation caused abnormal modifications of tau functioning, these processes work in tandem, amplifying each other’s detrimental consequences and causing the intellectual loss associated with AD (Mir et al., 2018; Mir). The evolved Aβ are further deposited in hippocampus and basal segment to form amyloid plaques and recruits the Aβ insoluble aggregates and hence damage to mitochondria resulting in severe decline in production of ATPs (Mir et al., 2021). Subsequently the astrocytes and microglia induce oxidation and inflammatory related reactions after activation leading to dysfunctioning of neurons and their apoptosis to lead clinical features of Alzheimer’s disease. Additionally, Aβ activate tau protein kinase which in turn phosphorylates the tau proteins (Shao and Xiao, 2013).

Following an extensive investigation into the processes of Aβ peptide-related damage, the underlying mechanisms that induce toxicity remain unknown. Researchers have indicated that Aβ aggregate receptor interaction influences several critical neuronal processes, but they haven’t disclosed the whole profile of these receptors or the associated signal transduction pathways linked with them, implying that further investigation is necessary (Yadav, 2021). The complexity of neurodegeneration is not fully decoded and therefore we have various hypothesis that attempts to decipher the pathophysiology of AD. The pathogenesis of Alzheimer’s disease is shown in Figure 3.

Cholinergic synapses are omnipresent in the brain, nerve cells, and spinal cord. This synaptic conduction is essential for cognition, concentration, memory, attention, and other superior cognitive mental abilities. Multiple studies imply that cholinergic synaptic transmission plays a key role in enhancing cognitive performance, brain functioning, and plasticity. As a result, subsequent research is oriented toward investigating the normal cognitive abilities and age-associated cognitive impairments caused due to the brain’s cholinergic system (Kaur et al., 2021; Pluta et al., 2021). The cholinergic theory transformed Alzheimer’s investigational studies from an observational and explanatory neuropathological study to the present paradigm of synaptic neurotransmission. The identification of rapidly depleting pre-synaptic cholinergic markers in the cerebral cortex (Scheltens et al., 2016), validation of Nucleus Basalis of Meynert (NBM) as the provenance of cortical innervation and the affirmation of its neurodegeneration specific to AD (Fu et al., 2017). Further, corroborating the cognitive decline caused due to cholinergic antagonists are the breakthrough discoveries supporting this hypothesis (Kaur et al., 2021). According to researchers, cholinergic synaptic transmission (CST) is important to cultivate memory as well as establishing learning abilities and any dysfunction in this system results in cognitive decline. In AD, neurodegeneration in the basal forebrain and the hippocampus region is substantial (Bennett et al., 2017). The acetylcholine (ACh) produced during CST is hydrolyzed by acetylcholinesterase AChE and butyrylcholinesterase (BuChE) to terminate the signal conduction. The BuChE levels are either elevated or unaltered in AD patients. AChE agglomeration promotes the AD neurotoxic A fibrils, as AChE is fundamental for the production of neurotoxin A fibrils (Bloom, 2014).

The pathophysiology of tau is initiated in the human brain even before the development of Aβ plaques, specifically aspiring the glutamate projection neurons. The aberrant phosphorylation of the tau among susceptible nerves in elderly rhesus macaques is linked to calcium imbalance (Hunt and Castillo, 2012; Vergara et al., 2019). The endosome that incorporates APP (Amyloid Precursor Protein) are confined by the improperly phosphorylated tau (pTau) on the microtubules, which eventually enhance Aβ synthesis. The aberrant tau phosphorylation caused by Aβ oligomers contributed to the pathogenesis of AD (Ferreira et al., 2015). Tau is a phosphoprotein composed of a microtubule-binding domain (MBD) and a projection domain in the brain, it entails 38 phosphorylation sites and has 6 isoforms composed of 352–441 amino acids. Additionally, the projection domain is separated into the proline-rich residual region and amino-terminal region. The tubulin-binding and carboxy-terminal regions encompass the MBD. Tau protein that has phosphorylated interfaces with tubulins to reinforce the assemblage of microtubules at the axon and is implicated in intracellular trafficking (Hampel et al., 2019). Normal tau is modified to paired helical filament tau (PHF-tau) and neurofibrillary tangles as a consequence of aberrant tau phosphorylation (NFTs). Hyperphosphorylated tau drastically alters microtubules and causes their deformation, ultimately culminating in the death of nerve cells. The proportion of hyperphosphorylated tau in an AD patient’s brain was 3–4 times greater than in a healthy brain (Hampel et al., 2018).

The identification of amyloid-β as the principal constituent of senile plaques and tau protein was proved to be a cardinal element of the NFTs was a major milestone in AD research as it provides significant insights about the pathophysiology of AD. This was followed by the discovery of genetic variations in the APP which directed the research toward autosomal dominant familial Alzheimer’s disease. These findings, coupled with other research findings, observations, and assumptions have fostered the amyloid hypothesis, which posits that amyloid-beta is the principal component that facilitates the pathogenesis of Alzheimer’s disease (Bowen et al., 1976; Whitehouse et al., 1981). The discrepancy in the rate of Aβ42 and related Aβ proteins synthesis and elimination is the driving factor to initiate AD. APP695, APP751, and APP770 are the three isoforms of APP that are indispensable for neurogenesis, synaptic plasticity regulation, cell attachment, and intracellular stabilization of calcium ion levels. APP (soluble) exerts neurotrophic and neuroprotective effects (Kilimann et al., 2014). The primary amyloidogenic pathway generates soluble βA protein and C-terminal α residues by separating the Lys16 residue from APP utilizing the enzyme α-secretase. The non-amyloidogenic peptide p3 is then produced by the degradation of the C-terminal component α by the enzyme γ-secretase. When β-secretase degrades APP, it creates soluble βA peptides and the C-terminal β residues.

The latter is fragmented at numerous locations by the catalysis of γ-secretase, yielding in βA monomers, which contain 38–43 amino acid residues. Self-assemblage of the βA monomers into neurotoxic oligomers, proceeded by the development of fibrillary clusters, induces neural impairment, which eventually leads to dementia. The clustered oligomers also stimulate the production of amyloid plaques, which are a hallmark of AD. In AD patients, concentrations of the βA42 peptides are seen to be higher. The primary form of APP in the brain is a 695 amino acid membrane protein that is systematically broken by 2 specific enzymes amyloidogenic pathway, i.e., the β-site APP cleavage enzyme (BACE) and γ-secretase. It can be concluded that the underlying mechanism implicated in AD pathogenesis is the generation of insoluble βA peptides via disintegration of APP (Jiang et al., 2017). Further, current aim of therapeutic strategies is to overcome the global AD prevalence is to decrease the formation and subsequent aggregation of Aβ and their clearance from AD patients (Jakob-Roetne and Jacobsen, 2009; Morris et al., 2018; Barthélemy et al., 2019; Arnsten et al., 2021).

Anti-amyloid approaches were employed in the past to treat AD, but the outcomes were unsatisfactory. As demonstrated by autopsy and imaging experiments, the amyloid cascade hypothesis isn’t adequate to describe neural destruction in AD. Neuroinflammation has a key part in Alzheimer’s disease, however, the exact influence of neuroinflammation, presumably beneficial or detrimental, is still being questioned (Savelieff et al., 2018). The advent of neuroinflammation has been corroborated by investigations that reveal tissues of CNS has a sophisticated and naturally adaptable capacity to modify its fundamental paracrine systems through independently created and modulated inflammatory chemicals (Gallardo and Holtzman, 2019).

Neuroinflammation has distinct traits based on fundamental reasons, such as its persistence, intensity and severity of occurrence, and duration time. Age-associated deterioration of anti-inflammatory pathways generates inflammation and develops mild clinical signs, such as neural inflammatory responses followed by severe brain damage, which can persevere for few years before its clinical presentation as AD (Hampel et al., 2018). Overexpression of microglial cells and astrocytes promotes prolonged and recurrent neuroinflammation by releasing proinflammatory cytokines such as interleukins, TNF-α, and γ-interferon, which influence the central nervous system are detected in AD patients. The γ-secretase activity cleaves APP to generate βA peptides, which are stimulated by reactive oxygen species (ROS). The anti-inflammatory methodologies are implemented to produce new compounds to address AD (Barage and Sonawane, 2015).

The brain is highly susceptible to oxidative damage in comparison to other organs, as the constituents of nerve cells are oxidized in Alzheimer’s due to alterations in the functioning of mitochondria, which subsequently elevates the level of metal ions, inflammatory molecules, and β-amyloid (Aβ) proteins (Villaflores et al., 2012). Oxidative stress exerts a critical role in the development of AD. An accelerating accumulation of tau hyperphosphorylation, and consequent decrease of synaptic connections and neuronal cell, oxidative damage accelerates the pathogenesis of AD. Various experiments have validated the irreversible and severe damage of nerve cells caused due to oxidative stress (Lin et al., 2011). AD is a condition of aberrant aging and exhibits oxidative injury at concentrations that far exceed those of senior individuals (controls), implying the presence of other unknown factors that could have positively contributed to the pathogenesis of the disorder (Lin et al., 2011; Villaflores et al., 2012). The degradation of synaptic plasticity in the afflicted areas of the brain is thought to be the initial factor that prefaces neurodegeneration in AD, and it is linked to cognitive dysfunction. Oxidative stress advances the process of aging and the development of a plethora of neurological illnesses, notably Alzheimer’s disease. Excessive generation of reactive oxygen species (ROS) is linked to age/disorder-related mitochondrial dysfunction, disrupted mental equilibrium, and diminished antioxidant defense, which influences synaptic plasticity and neurotransmission, which directs toward cognitive impairment (Selkoe, 1991).

Reactive oxygen species also modulates DNA, triglycerides, peptides, amino acids, calcium levels, functioning efficacy and kinetics of mitochondrial, cellular morphology, receptors traffic, and energy balance, among other molecular targets (Hardy and Higgins, 1992).

The reported preventative properties of natural products are resultant of anti-oxidative or anti-neuroinflammatory effects, which action by blocking the agglomeration of Aβ and tau peptides and boosting cholinergic signaling. Natural compounds that tackle several pathogenic pathways may be capable of reducing/delaying or even preventing the occurrence and advancement of Alzheimer’s disease (Graham et al., 2017). Owing to the unavailability of efficacious pharmacological interventions for AD, alternative initiatives centered on diet modifications, intake of food supplements, consumption of functional food ingredients and organic products to avoid the disease conditions (Karran et al., 2011). Novel medications are critical for enhancing the quality of care and alleviating the symptoms of affected individuals. Multiple pharmacological options to diagnose and control Alzheimer’s disease are presented in recent times, but none have yielded optimistic results in clinical studies.

Recent studies have revealed that some dietary factors lower the incidence of AD, which has motivated scientists to investigate the benefits of phytoconstituents and extracted bioactive elements (Hensley, 2010; Calsolaro and Edison, 2016).

Natural remedies, have potential drug-like qualities, that enable them to pass the biological membranes, and allow them to interfere in protein-protein associations (Chen and Zhong, 2014; Wang X. et al., 2014; Calsolaro and Edison, 2016). Chemicals derived from different plant parts, including the roots, bulbs, tubers, rhizome, foliage, pods, seeds, and buds inhibit harmful amyloid plaque development and increase cholinergic signaling (Tönnies and Trushina, 2017). Antioxidant-rich foods have been shown to lower oxidative damage in the CNS. As a result, natural compounds have a wide spectrum of pharmacological effects, drawing the interest of scientists who want to use them in the production of therapeutic molecules to cure a variety of ailments (Kennedy and Wightman, 2011; Grant, 2016; Bhat et al., 2021; Chen X. et al., 2021).

The use of food and other natural sources as supplements to address several conditions is a traditional knowledge used in Ayurveda, Siddha, Unani, Chinese Herbal Medicines, and others in conventional traditional practices. Over the decades, the approach of utilizing these bioactive phytocompounds is changing constantly. Previously, the research was mainly centered on demonstrating various pharmacological properties of a different plant parts or of the whole extract itself (Vassallo, 2008; NewmanDj, 2016; Mir et al., 2021a). Presently, with the emergence of nutraceuticals, the applications of bioactive phytocompounds are not just limited to the consumption of natural products as dietary supplements, but to explore their specific therapeutic properties to develop potential drugs. With the vast diversity of bioresources, we have various plants, herbs, fruits, vegetables, seafood, meat, dairy products, nuts, berries, etc., are all rich with various phytocompounds which have neuroprotective properties are shown in Figure 4.

The key domain of investigation in AD pathophysiology is treatment techniques targeting Aβ oligomers. Various treatment techniques are employed, including blocking Aβ production (Silva et al., 2014) to reduce Aβ oligomers, lowering soluble levels of Aβ, and eliminating Aβ from the brain (Yang et al., 2016). AD causes neuroinflammatory reactions, mitochondrial malfunction, oxidative stress, loss of synaptic plasticity, transportation, and tau hyperphosphorylation, in addition to other associated cellular abnormalities. Aβ is produced as a predictable consequence of these physiological modifications (Tariq et al., 2021). Numerous botanical herbs demonstrated anti-amyloidogenic properties, indicating its influences on the accumulation and instability of pre-existing Aβ fibrillary aggregates in the CNS (Maccioni et al., 2010; Mir et al., 2021b; Nomoto et al., 2021; Wainwright et al., 2022). Aside from the medicinal herbs listed, studies have investigated the anti-amyloidogenic properties of ellagic acids, garlic acid, dry ginger extract, isolates of mulberry leaf, and caper buds, which are all consumable dietary elements (Fujiwara et al., 2006, 2009; Papandreou et al., 2006).

Targeting BACE-1 or γ-secretase enzymes is identified as the most effective treatment method for AD because Aβ build-up leads to aberrant enzymatic cleavage of APP by β- and γ-secretase enzymes, resulting in the production of Aβ oligomers (Durairajan et al., 2008; Fujiwara et al., 2009). Several herbal extractions that combine with β-secretases impact Aβ synthesis. Ellagic acid and punicalagin were reported to suppress β-secretase in, Punica granatum L. (Lythraceae). Lipophilic alkylated flavonoids from S. flavescens Aiton (Fabaceae) have a strong non-competitive BACE-1 inhibition effect. Polyphenols derived from green and black tea, as well as Smilax china L. (Smilacaceae), are effective BACE-1 inhibitors, which aids in slowing the advancement of Alzheimer’s disease.

Tau peptides action to stabilize microtubules, but their aberrant hyperphosphorylation causes tau agglomeration. AD is caused by these aggregates and constraining the development of tau clusters, controlling tau with kinases, limiting tau disintegration with chaperones, and stabilizing tau microtubules are successful methods to address post-symptomatic AD. Anti-tau effects have been demonstrated in herbal medications and extracts. Curcumin, a diarylheptanoid identified in turmeric (Curcuma longa) extracts, stimulates the generation of the anti-inflammatory IL-4 cytokine and lowers Aβ and tau concentrations in mice with Aβ overexpression (Kang et al., 2011).

The cinnamon (Cinnamomum zeylanicum) extraction inhibited tau assembly and additionally exhibited the inhibitory effect that is attributed to both cinnamaldehyde and procyanidin. The bioactive constituent paclitaxel, derived from Taxus brevifolia, exhibited therapeutic properties by combatting the functional loss in the tau pathology (Kang et al., 2011).

Severe oxidative damage in AD pathogenesis stimulates the production of reactive oxygen species (ROS) by activating microglial cells with Aβ oligomers (Syad and Devi, 2014). For instance, the validated efficacy of Ginko biloba contained metabolites such as, tocopherol, bioflavonoid pycnogenol, ascorbyl palmitate and other antioxidants ineffectively suppressing the apoptotic cells in the hippocampus of ApoE-deficient mice. Similarly, Salvia officinalis is notable for its antioxidant properties, anti-inflammatory characteristics, and mild suppression of AChEs (Fujiwara et al., 2009). The active element in sage, rosmarinic acid, inhibits the development of ROS, peroxidation of lipids, activation of caspase-3, fragmentation of nucleic acids, and Aβ oligomeric hyperphosphorylation of tau protein (Fujiwara et al., 2009). Panchagavya Ghrita, an Ayurveda composition, reduces seizures, cognitive decline, and oxidative damage (Joshi et al., 2015). As discussed in this review there are ample number of natural products that are neuroprotective in nature. The neuroprotective properties of some common fruits, vegetables, herb, berries, nuts species, and condiments are discussed in the proceeding section.

As discussed earlier a number of plant-derived or natural bioactive phytocompounds like phenols, alkaloids, strolls, carotenoids, flavonoids, etc., have cytoprotective, neuroprotective properties due to their antioxidant, anti-inflammatory, anti-apoptotic, properties. Origins and chemical structures of discussed phytochemicals were shown in Table 3 and Figure 5 and the mechanism of phytochemicals against AD is depicted in Figure 6.

Besides intervening as muscarinic receptor agonists, anti-oxidants, anti-amyloid inhibitors, AChE and BuChE inhibitors, α-synuclein agglomeration inhibitors, dopaminergic and nicotine agonists, alkaloids help to alleviate the pathophysiology of AD (Rahman and Muralidharan, 2010).

Alkaloids have a broad spectrum of therapeutic potency in biomedicine, including analgesics (e.g., morphine), anti-diabetic (e.g., piperine), anti-tumor (e.g., berberine), and anti-microbial effects (e.g., berberine) (e.g., ciprofloxacin). Certain alkaloids have both stimulating and neuropsychiatric effects on the central nervous system (e.g., cocaine, caffeine, and nicotine) (e.g., psilocin). Despite the fact that alkaloids have a strong tradition and a wide range of properties, few are presented as functional and efficient medicines. They have a wide range of protective effects in conditions like seizures, psychiatric problems, cerebral ischemia, Alzheimer and memory lapses, anxiety, stress, and many more. Alkaloids suppress the establishment of neurodegenerative disorders by multiple mechanisms, including blocking the AChE, boosting GABA levels, and acting as NMDA antagonists (Rahman and Muralidharan, 2010; Liu et al., 2018).

Multiple research and clinical trials have validated that essential oils have positive benefits in AD patients. Plant essential oils and specific terpenes have been demonstrated to have antioxidant and AChEIs properties (Asgarpanah and Kazemivash, 2012). Effective anti-AD compounds include terpenoids such as ginsenosides, ginkgolides, and cannabinoids. Ginsenoside Rg3 (minimizes Aβ production by 84 percent in CHO-2B7 cells and by 31 percent in Tg2576) transgenic mice (Kulkarni et al., 2011; Avneet et al., 2018). Ginsenoside Rg3 lowers Aβ concentration by boosting Aβ breakdown and by increasing the production of neprilysin, a rate-limiting enzyme in Aβ degradation. PC12 cells are protected from Aβ-induced neurotoxic effects by ginsenoside Re. Moreover, ginsenoside Rb1 reduces neuroinflammatory biomarkers in the hippocampal cells, by reversing Aβ-induced cognitive impairment in mice. By boosting synapse plasticity in the brain, ginsenoside Rb1 has a positive influence on spatial working memory (Ng et al., 2015; Lima and Hamerski, 2019). Ginkgolides is a labdane-form of cyclic diterpenes that are often extracted from Ginkgo biloba. Ginkgolide A and B therapy preserves nerve cells from synaptic injury as measured by synaptophysin loss, a presynaptic synaptic indicator, and enhances nerve cell survival despite A-induced toxicity. Ginkgolide B protects hippocampus nerve cells against Aβ-directed cell death by boosting the synthesis of brain-derived neurotrophic factors and by reducing nerve cell apoptosis in hemorrhaging rat brain cells (Yoo and Park, 2012).

Resveratrol is proven to suppress the expression of pro-inflammatory molecules such as NF-kB and TNF-α in glial cells, while also increasing the amount of the anti-inflammatory cytokine IL-10, which is linked to Alzheimer’s diseases. Resveratrol improves spatial cognitive performance in Alzheimer’s disease rats via increasing anti-oxidant function. Resveratrol aids in the expression of SIRT1, which increases the preservation of nerve cells against ROS, free radicals, and Aβ -generated inflammation of the nerve cells (Chen et al., 2006; Awasthi et al., 2018). Oxyresveratrol, a compound derived from the Morus alba tree, reduces the production of the iNOS molecule in LPS- mediated macrophages, hence inhibiting the NO generation. Moreover, Oxyresveratrol has neuroprotective properties against Aβ protein-mediated neurotoxic effects in the cortical nerve cells, and anti-inflammatory and anti-apoptotic properties by lowering TNF-α, IL-1β, and IL-6 secretion and inhibiting caspase-1 and NF-kB expression (Chen et al., 2006). For its antioxidant capacity, ROS (OH, superoxide anions) scavenging effects, transversal BBB quercetin has been shown to have neuroprotective properties. Quercetin’s neuroprotective properties are mostly demonstrated through the dysregulation of cytokines via (MAPK) signaling pathways and p13K/Akt networks. Quercetin is also documented for inhibiting the LOX and COX proteases, which are related to the process of eicosanoids and the induction of NF-kB (Wang et al., 2011).

Alzheimer’s is a complex, slow-progressing neurological illness. Even though AD associated pathologies are not greatly explored, current findings approved several factors responsible for its clinical manifestations. Multiple treatment strategies are explored at different stages as potential medication therapeutic interventions to successfully combat and control AD. FDA anti-AD medications deliver symptomatic treatment but have their drawbacks and side effects like nausea, vomiting, dizziness, headache, loss of appetite, loss of weight, diarrhea, etc. As a result, innovative alternate treatment techniques utilizing herbal medications to address AD is needed. Proper intervention in accordance with diseases progression ameliorates disease management. The irreversible damage to the brain cells and involuted pathophysiological, events associated with AD have always emphasized the need for the development of novel drugs and therapeutics, which render better outcomes with fewer or no side effects. Natural compounds and their bioactive phytochemicals have been shown to have significant neuroprotective potential in the treatment and management of AD, with limited negative side effects. Significant pharmacological properties like neuroprotective, anti-oxidant, anti-inflammatory, anti-apoptotic, etc., demonstrated by phytonutrients like tannins, alkaloids, phenols, carotenoids can be inspected to devise potential drugs. The degenerative pathway connected with Alzheimer’s disease is thought to be complex, despite the fact that it is not entirely comprehended. For the diagnosis and intervention of AD, neuroprotective treatments encompassing several molecular pathways are crucial. In the development of anti-AD drugs, organic product combinations or preparations containing several active pharmacological ingredients having the potential to execute diverse neuroprotective pathways and restorative mechanisms are sought. Green therapy could play a significant role in precluding AD and in devising therapeutics for symptom and disease management with the establishment of QA (Quality Assurance) and QC (Quality Control) guidelines to ensure the development of a safe and effective novel neuroprotective drugs. Our review strongly backs up use of medicinal plants and phytoconstituents alone or in combination with other compounds for effective treatments against Alzheimer’s disease with lesser side effects as compared to currently available treatments.

MM designed and supervised the study, and made a substantial contribution to the concept of study, and revision of the manuscript thoroughly. BB and AA equally contributed to this work in the analysis and writing of the manuscript. MM, BB, RM, WM, FA, and BA performed interpretation, drew the figures and tables, and critical review and drafting of the manuscript. All authors listed have made a substantial, direct, and intellectual contribution to the work, and read and approved the final manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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