Natural Products-based Drugs: Potential Drug Targets Against Neurological Degeneration

Abstract

Phytochemicals or natural products have been studied extensively for their potential in the treatment of neurodegenerative diseases (NDs) like Parkinson’s disease, Alzheimer’s disease, etc. The neuronal structure loss and progressive dysfunction are the main characteristics of these diseases. In spite of impressive and thorough knowledge of neurodegenerative molecular pathways, little advancement has been found in the treatment of the same. Moreover, it was proved that natural products can be used efficiently in the treatment of NDs while certain issues regarding the patient's safety and clinical data are still existing. As ND is a bunch of diseases and it will start the myriad of pathological processes, active targeting of the molecular pathway behind ND will be the most efficient strategy to treat all ND-related diseases. The targeting pathway must prevent cell death and should restore the damaged neurons. In the treatment of ND and related diseases, natural products are playing the role of neuroprotective agents. This review will target the therapeutic potential of various phytochemicals which shows neuroprotective action.

1. INTRODUCTION

Neurodegenerative disorders (NDs) are a group of chronic, progressive central nervous system disorders, characterized by the degradation, and subsequent loss of neurons. NDs are an increasing source of death and morbidity worldwide, especially among the elderly, making them one of the most promising public health issues. Because of their irreversibility, lack of effective treatment, and associated social and economic consequences, age-related diseases such as NDs are becoming increasingly relevant. Acute neurodegeneration is a disorder in which neurons are injured rapidly and frequently die as a result of traumatic events including, strokes, head injury, traumatic brain injury, ischemic brain damage, and cerebral or subarachnoid hemorrhage. Whereas, chronic neurodegeneration is a long-term condition in which neurons in the nervous system experience a neurodegenerative process that begins slowly and worsens over time due to a variety of factors, resulting in the irreversible death of explicit neuron inhabitants. Chronic neurodegenerative disorders include Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, and Huntington’s disease [1].

Alzheimer’s disease is an age-related, chronic, and progressive neurological illness that causes memory and cognitive impairments, as well as behavioral changes. It is characterized by two important neuropathological characteristics such as production and deposition of the extracellular amyloid-beta (Aβ) plaques in the brain, and protein accretion of intracellular hyperphosphorylated tau proteins termed neurofibrillary tangles. Parkinson’s disease is a chronic and progressive neurological illness that affects motor functioning by causing a progressive loss of dopaminergic nigrostriatal neurons. It causes bradykinesia, postural imbalance, resting tremor, and muscular rigidity. Parkinson's disease is distinguished by the accretion of Lewy bodies, Lewy neurites, and intracellular protein aggregates, which are primarily composed of the misfolded and aggregated forms of presynaptic protein alpha (α)-synuclein, as well as the progressive loss of dopaminergic nigrostriatal neurons [2, 3].

Amyotrophic lateral sclerosis (ALS) is another progressive neurodegenerative disorder that is characterized by the progressive degeneration and death of upper and lower motor neurons, leading to paralysis and death from respiratory failure. The mechanisms underlying amyotrophic lateral sclerosis are unknown, but several factors such as genetic factors, oxidative stress, excitotoxicity, impaired axonal transport, autoimmune response, environmental factors, mitochondrial dysfunction, and neurofilament aggregation have been considered. Amyotrophic lateral sclerosis is allied to a mutation in the gene that codes for the copper/zinc superoxide dismutase-1 (SOD1) enzyme. Whereas, Huntington’s disease is a condition of neurological illness that is pathologically defined by enhanced dopaminergic activity and reduced gamma-aminobutyric acid (GABA) functioning in the basal ganglia, and clinically defined by psychiatric disturbances, cognitive deficits, and abnormal movements. It is triggered by a trinucleotide reiteration development of the nucleotide’s cytosine, adenine, and guanine (a CAG expansion) in the Huntingtin (HTT) gene, which is located on the petite arm of chromosome-4 [4-8].

2. POTENTIAL DRUG TARGETS OF NATURAL PRODUCTS FOR NEURO REGENERATION AND THEIR MECHANISM OF ACTION

Neurodegenerative disorders are characterized by protein aggregates and inflammation, as well as oxidative stress (OS) in the central nervous system. Several biological progressions are associated with neurodegenerative disorders including neurotransmitter diminution or inadequate synthesis, oxidative stress, and atypical ubiquitination. The mechanisms underlying neurodegenerative diseases are intricate and multifactorial. NDs exhibit some communal characteristics such as abnormal cellular transport, abnormal protein deposition, inflammation, mitochondrial deficits, intracellular Ca²⁺ overload, excitotoxicity, and uncontrolled generation of ROS, implying the existence of converging neurodegeneration pathways and emphasizing the characteristics of these pathways as common targets for intervention tactics. The therapeutic drug targets and their mechanisms associated with the neurodegeneration that are implicated in the progression and pathogenesis of neurodegenerative disorders are described in Fig. (1).

Fig. (1).

Therapeutic drug targets and their mechanisms associated with neurodegeneration.

Investigations based on natural products and their metabolites have been demonstrated to be an effective methodology in the development of newer, novel, physiologically active, and innovative medications. Natural product-based drug discoveries have sparked a lot of interest over the last three decades. According to an investigation, at least one-third of the marketed drugs have originated or derived from various natural resources. Natural products and their isolated natural compounds have the potential to be neuroprotective and therapeutic agents as well as valuable resources for drug discovery against various neurodegenerative diseases. The therapeutic potential of natural products and their bioactive compounds to exert a neuroprotective effect on the pathologies of neurodegenerative disorders is described in Table 1 [9].

Table 1.

Natural products and their bioactive compounds with neuroprotective activities in the treatment of neurodegenerative disorders.

S. No.	Phytochemicals/ Natural Products	Treatment of Diseases	Neuroprotective Activities	References
1.	Capsicum annuum (Solanaceae)	Parkinson’s disease	Prevented the neuronal degeneration in substantial nigra, cerebral cortex, and hippocampus by attenuating brain 5-lipoxygenase activity, inhibited the increase of brain malondialdehyde and nitric oxide levels, restored the brain GSH level, cholinesterase activity, and paraoxonase-1 (PON1) activity.	[1]
2.	Curcuma longa (Zingiberaceae)	Alzheimer’s and Parkinson’s disease	Improvement in motor performance and gross behavioral activity reversed GFAP and iNOS protein expressions, prevented the depletion of dopamine and tyrosine hydroxylase immunoreactivity, and reduced proinflammatory cytokines and total nitrite generation in the striatum.	[2, 3,4]
3.	Tinospora cordifolia (Menispermaceae)	Parkinson’s disease	Reduced oxidative stress, increased dopamine levels and complex I activity, and restored 6-OHDA-induced behavioral changes in locomotor activity.	[6, 7, 8]
4.	Apium graveolens (Apiaceae)	Parkinson’s disease	Attenuation of oxidative stress reduced monoamine oxidase activity, and protected dopaminergic neurons.	[9]
5.	Osmotin (Nicotiana tabacum)	Alzheimer’s disease	Attenuation of Aβ accumulation and BACE-1 expression ameliorated memory impairment, prevented Aβ-induced neurotoxicity of neuronal HT22 cells and primary cultures of hippocampal neurons, and reversed synaptic deficits.	[12]
6.	β-Caryophyllene	Parkinson’s disease	Attenuation of proinflammatory cytokines (IL-1b, IL-6, and TNF-α) in midbrain tissues and inflammatory mediators (COX-2 and iNOS expressions) in the cytoplasmic fraction of striatal tissue lysates, prevented the dopaminergic neuronal loss in the substantia nigra and striatal dopamine fibers, restored antioxidant enzymes and glutathione depletion and inhibited lipid peroxidation.	[3, 9]
7.	Tribulus terrestris (Zhygophyllaceae)	Parkinson’s disease	Attenuation of inflammatory markers (iNOS and COX-2 mRNA expression), suppression of oxidative stress by increasing GSH and superoxide dismutase and catalase activities, ameliorated motor dysfunction, downregulation of CD11b mRNA expression (microglia marker), and improved striatal dopamine level.	[6, 13]
8.	Methanolic extract of Lactuca capensis	Alzheimer’s disease	Attenuation of hippocampal apoptosis by lowering the enrichment factor of apoptosis, ameliorated cognitive impairment and memory deficits, decreased the lipid peroxidation and protein oxidation level, and acetylcholinesterase activity, and restored the level of GSH and activities of antioxidant enzymes (superoxide dismutase and glutathione peroxidase).	[14]
9.	Nigella sativa (Ranunculaceae)	Lateral and Multiple Sclerosis	Enhancement of remyelination in the cerebellum, decreased transforming growth factor beta-1 (TGF-β1) expression and suppressed inflammation.	[15,16]
10.	Safflower yellow	Alzheimer’s disease	Downregulation of M1 microglial markers (iNOS and CD86) and upregulation of M2 microglial markers (arginase-1, CD2066, and YM-1), decreased inflammatory markers (iNOS, IL-1β, IL6, and TNF-α levels), reduced neuronal cell loss in hippocampus and cortex, and inhibited the activation of glial cells.	[17-19]
11.	Isogarcinol (Garcinia mangostana)	Lateral and Multiple Sclerosis	Alleviation of inflammation and demyelination in the brain and spinal cord, reduced number of cells differentiation by inhibiting Janus kinase (JAK)/ signal transducers and activators of transcription (STAT) signaling pathways, and reduced the activation of CD4+ and CD11b+ cell populations.	[20, 21, 25, 26]
12.	Rosmarinic acid	Parkinson’s disease	Upregulation of the ratio of Bcl-2/Bax gene expression in the substantia nigra, increased the number of tyrosine hydroxylase, decreased the iron level in the substantia nigra, and restored striatal dopamine level.	[26, 27]
13.	White grape (Vitis vinifera)	Lateral and Multiple Sclerosis	Reduced TNF-α, iNOS, and PARP expression and nitro-tyrosine level, and inhibited the apoptosis (caspase-3 and Bcl-2 expressions).	[21, 22]
14.	Huperzine A (Huperzia serrata)	Alzheimer’s disease	Improvement in memory, cognitive, and behavior functions, protects neurons from cytotoxicity and apoptosis, reduced Aβ-induced neuronal cell death, inhibited glutamate toxicity, and decreased oxidative damage.	[21, 26]
15.	Walnut extract	Lateral and Multiple Sclerosis	Downregulation of iNOS and Iba-1 expressions, and upregulation of calmodulin expressions.	[23a,b]

3. CLINICAL TRIALS ON VARIOUS NATURAL PRODUCTS FOR THEIR NEURO REGENERATIVE EFFECTS/NEUROPROTECTIVE EFFECTS

Several possible interventions aimed at various targets are being developed and tested in ongoing clinical trials, including anti-amyloid and anti-tau interventions, cognitive enhancement, anti-neuroinflammation and neuroprotection interventions, neurotransmitter modification, and interventions to relieve behavioral psychological indications. The status of clinical studies on various natural products and their mechanism of action in the treatment of neurodegenerative disorders are described in Table 2.

Table 2.

Clinical studies on Natural products/phytochemicals used in the treatment of neurodegenerative disorders.

S. No.	Phytochemicals	Mechanism of Action	NCT Number	Status
1.	Ginkgo biloba	Antioxidant and anti-amyloid aggregation	NCT03090516	Recruiting
2.	Guanfacine	Alpha-2A-adrenoceptor agonist, a potent 5-HT2B receptor agonist	NCT03116126	Recruiting
3.	Coconut oil	Reduction in ADP-ribosylation factor 1 protein expression	NCT01883648	Terminated

4. NEUROPROTECTIVE EFFECTS OF VARIOUS NATURAL PRODUCTS

A no. of natural products can elicit neuroprotective effects for the prevention of neurodegeneration. The use of natural products is widely supported by literature-based facts as they elicit various activities by different mechanisms and due to their multiple mechanisms of action, they do not cause resistance to the therapy and also the side effects of the natural products are minimal. Fig. (2) depicts the mechanism of action and the neuroprotective effects of various natural products [4].

Fig. (2).

Mechanism of Neurodegeneration and the role of natural products as neuroprotective.

The various natural (herbal compounds) eliciting a no. of mechanisms to act as neuroprotective are mentioned below:

• Resveratrol

• Quercetin

• Genistein

• Luteolin

• Apigenin

• Hesperidin

• Cyanobacteria

• Marine Macroalgae

• Other natural compounds

4.1. Resveratrol

Resveratrol (RSV) belongs to the class of phenolic stilbene compounds which is found in most of the flavonoid compounds of red wine, grapes, and nuts. A number of researchers had worked on RSV and they reported RSV to possess various activities like anticancer, antioxidant, neuroprotective, cardiovascular, antidiabetic, and many other effects. RSV works by scavenging reactive oxygen species (ROS) from the blood and thereby increasing the glutathione (GTH).it was found that the nanocapsule loaded RSV has more brain targeting efficacy as compared to the free RSV. The bio absorbance of RSV is good in the gastrointestinal tract but due to their rapid metabolism and clearance from the body, RSV lacks bio specificity. RSV was proven to reduce the inflammatory response by suppressing nitric oxide, Tumor necrosis factor and interleukins (IL-1B and IL-6) of astrocytes. Also, the removal of nuclear factor kappa B (NF-KB) also decreases the production of TNF and ILs. One study also revealed the fact that RSV significantly decreases the profile of mood states (POMS) and other fatigue and related properties but has no impact on memory and performance [10-13].

4.2. Quercetin

Quercetin (QCT) is a very well-known flavonoid compound that occurs in many herbs such as apples, red and black berries, pasta, tomatoes, and grapes. It is the most common flavonoid found in edible plants and is well known for its antioxidant properties. It had been reported that QCT enhances memory, learning properties, and consciousness in patients with neurological disorders such as Alzheimer’s disease. Pharmacologically, QCT posses antiviral, anticancer, antioxidant, anti-inflammatory, and anti-amyloid effects. It was reported to induce the removal of end products of plasma daily with a half-life of 11-28 hours which makes it available to the body daily by the production inside the body. The higher amount of QCT can cross blood-brain barrier (BBB) when entrapped in liposomal preparations as compared to the free QCT which can further enhance the chances of higher neurotoxicity. In scopolamine induce loss impairment of memory in zebrafish, QCT was found to have memory-boosting effects with improved chlorogenic neurotransmission, found in one study. Moreover, there was a further need to have the toxicity data of the drug to determine its safety: toxicity data of the drug. It was observed the beta-mediated apoptosis was significantly reduced at the lower doses of the drug while the cytotoxicity was induced at the higher doses of the same. The ability of QCT to cross the BBB and the residence period & quantity of its metabolites in the brain are the most important factors in determining the dose of the QCT. Furthermore, the coadministration of alpha-tocopherol along with QCT was found to promote the crossing of BBB by QCT [2, 14-18].

4.3. Genistein

Genistein is abundantly found in soy isoflavone and is the type of bioflavonoid that exhibit multiple activities like antioxidant, anti-inflammatory, cardiovascular, anticancer, and proapoptotic properties like natural estrogen, protein tyrosine kinase inhibition activity and many other intercellular and intracellular activities. The evidences are there to support the fact that genistein inhibits various destructive conditions like atherosclerosis, estrogen deficiency and polycystic ovarian diseases, and hormone imbalanced diseases like hypothyroidism. Recently, the neuroprotective activity of genistein was evaluated by researchers. It was evaluated that genistein was effective in treating the neurotoxicity induced by a beta peptide in the neuronal cells of the wistar rats. It was also confirmed that genistein has the ability to cross the BBB and due to its antioxidant properties, it acts as a neuroprotective. Also, it can cross BBB, it was proven to be neuroprotective for a longer period of time [19-24].

4.4. Luteolin

Luteolin (Lu), being an isoflavone occurs in yellow color and crystalline appearance. It is commonly found in the families like Bryophyta, and Pteridophyte. In foods, it occurs in oregano, carrots, onion, olives, thyme, and peppermint, etc. it possesses various activities like antioxidant, neuroprotective, anti-inflammatory, anticancer, and anti-microbial properties, etc., and the antioxidant activity is associated with free radical scavenger activity of this plant. Due to this, Lu is able to remove the reactive oxygen species from our body and act as an antioxidant. This antioxidant action is one of the very important activities possessed by natural plants. The antioxidant action can serve as one of the important pathways in possessing the anticancer and neuroprotective action by the herb [25-27]. One study revealed the fact that Lu had directly inhibited the zinc-induced hypo phosphorylation not just because of its anti-oxidant activity but also through the regulatory mechanism of the tyrosine phosphokinase system. It was also reported that the BBB crossing activity of the Lu greatly enhanced when transported along with the Vitamin E Tocopherol [28-32].

4.5. Apigenin

Apigenin (Ap) is a subcategory of flavones and flavonoids. Very few evidences are there to support the fact that the Ap in the normal; diet can promote in vivo metabolic adverse reactions. Ap posses very important functions such as antioxidant, anti-inflammatory, anti-cancer, anti-proliferator, and anti-microbial properties. It also inhibits the strong metabolizing enzyme CYTP450 which is the metabolizer of many prescription-based drugs. Moreover, it was also revealed by the researchers that, Ap is water soluble and intestinal-permeable flavonoid. The different transporters present in the intestine can absorb as well as transport the Ap in a good manner and the duodenum is the main site for absorption. Apart from this, it also posses various activities like antioxidants, anticancer, neuroprotective, enzymes inhibitor, anti-genotoxic, and anti-proliferator, etc. [33-37].

4.6. Hesperidin

Hesperidin (Hes)occurs in flavone glycosides such as oranges, lemons, sweet oranges, and grapes. Hes is a great memory booster as the administration of Hes for 16 weeks in transgenic mice enhanced the memory by enhancing the recognition index. Hes also impaired the learning and memory impairment caused by AlCl₃ and thereby functions as an anti-acetylcholinesterase. It possesses neuroprotective activities which can be well correlated from the signals of upregulation of beta cell lymphoma and downregulation of associated protein Bax. It also was reported that Hes possess neuroprotective activity against various neurological disorders like cerebral ischemia. It mainly passes through BBB easily and inhibits the release of glutamate [38-42].

4.7. Cyanobacteria

Cyanobacteria are aform of bacteria that are closely related to bacterial forms, they are prokaryotic, prosynthetic, and self-producing species. They are commonly known as blue-green algae and the members of the Oscillatoria family. Researchers have shown a keen interest in blue-green algae owing to their vast pharmacological activities. Spirulina plantansis is a well-known member of blue-green algae which is well known for its nutritional values. It possesses anti-inflammatory and antioxidant properties that protect it against pathogens. Also, research has shown that polysaccharides derived from spirulina possess an antioxidant effect on the dopaminergic neurons rather than the inhibition of monoamine oxidase (MAO). Another research also revealed the fact that it protects the memory damage caused by scopolamine in mice. Due to their antioxidant effect, they impart neuroprotective effects. It can cross BBB as suggested by the presence of c-phycocyanin which is a product of spirulina, in the hippocampus. Also, it has shown cytoprotective activity against neurodegeneration via an antioxidant mechanism [38, 39, 43-45].

4.8. Marine Macroalgae

Marine macroalgae (MM) is a plant-like substance which is typically found in coastal areas and well-known by the name seaweed. The common three groups are there viz. green, brown, and red algae. The main components of MM are phenolic compounds, phenols, proteins, pigments and a variety of other compounds are also present. Research revealed the fact that the compounds have good health impacts. One study revealed the high radical scavenging activity of the carotenoids. To add further to this, many studies suggested that they enhance cell viability and decrease oxidative stress, and have a healthy mitochondrial potential. These statements suggest the neuroprotective impact of the algae due to their antioxidant potential. However, researchers focused on their commercial use and tend to formulate the drug delivery system of the formulations particularly the nano drug delivery systems for the bacterial algae. However, the use of marine algae as a commercial drug delivery system is limited because of its inability to cross BBB [45-49].

4.9. Astragalus Membranaceus 

Astragalus membranaceus (AM) is a terpenoid drug commonly used for recovery after a stroke in China. Clinical trials were performed to evaluate the clinical potential of the drug and the drug was found to be very effective in recovering patients after stroke [47, 50-53].

4.10. Other Natural Products as Neuro Protectives

A number of other compounds have been reported in the literature which possesses neuroprotective activities. Several compounds which treat neurodegeneration to a great extent are reported in Table 3. The main mechanism includes their anti-oxidant potential, mitochondrial stabilization impact, anti-proliferative, free radical scavenging activity, and anticancer potential.

Table 3.

Various plants and their products for their neuroprotective potential.

Sr. No.	Name of the Plant/Plant Part	Pharmacological Action	References
1	Extract of Yacon leaves	Prevents the memory defects	[18]
2	Aqueous extract of safflower	Improvement of short-term memory loss	[19]
3	Lactucacapensis thunb. leaves methanolic extract	Decrease the lipid peroxidation and protein oxidation	[20]
4	Haldi Powder	Improved quality of life	[2, 25]
5	Coconut oil	Improved cognitive functions	[21]
6	Osmotin	Enhanced random alterations	[26]
7	Brown rice (Germinated)	Reduced ROS activity	[27]

5. NATURAL COMPOUNDS TO MITIGATE EXCITOTOXICITY AND INFLAMMATION IN NEURODEGENERATION

Oxidative stress is responsible for the injury of vascular endothelium. It leads to tissue damage and occlusion of the artery followed by reperfusion. The specific reason behind this is the imbalance between the production and scavenging of the reactive oxygen species (ROS). Moreover, ischemic stroke happens as a result of the increased concentration of glutamate release which increases the concentration of Ca²⁺ ions. Furthermore, the elevated calcium ions result in the induction of enzymes such as proteases, phospholipase, and oxidase which further leads to the damage of DNA. Enhanced concentration of calcium ions also increases the concentration of lipid peroxidase (LPO) which further produces more free radicals and enhancement of oxidative stress also occurs in response to that. In lieu of this, some phytochemicals such as Mucuna pruriensplant or commonly known as velvet bean or Kapikacchu which contains a huge amount of natural antioxidants had proven to be beneficial in the reduction of oxidative stress and ROS. This is an Indian traditional herb that was previously used for the treatment of arthritis and depression and has shown its potential as a neurological substance due to its antioxidant activity [54-59].

6. ROLE OF NANOTECHNOLOGY-BASED DRUG DELIVERY FOR NEUROPROTECTIVE NATURAL PRODUCTS

The various phytoconstituents are responsible for a vast number of activities including their anticancer, antioxidant, and neuroprotective actions. However, their actions are restricted due to their solubility and bioavailability-related problems. Raw forms of natural products, if administered in the conventional forms, they suffered from the problem of bioavailability. Therefore, the lacks the scaleup from lab scale to commercialization. Nanotechnology has come up with the idea to overcome this problem. Nanotechnology-based drug delivery systems like nanosponges, nanoemulsions, nanogels, nano micelles, and nanoparticles can improve the solubility and specificity of the natural bioactive. Also, the active targeting concept has brought more specificity to the phytoconstituents. The compounds specifically attack their site of action and prevent the side effects [56, 60-64].

7. LIMITATIONS, CHALLENGES, AND FUTURE PROJECTIONS

The process of natural neuroprotection against various neurodegenerative diseases is widely accepted nowadays by using various natural herbs whole or using their products. Despite a number of favorable incidents depicting the use of natural herbs for the treatment of neurodegeneration, a successful transformation of these herbs from research to commercialization are still lacking as preclinical evidence are there but clinical testing of the same is still lacking. Natural products and their byproducts face many challenges from the point of view of their solubility, biostability, physical and chemical stability, metabolism, BBB crossing, and therapeutic efficacy. A number of natural compounds like resveratrol, turmeric, and apigenin possess numerous neuroprotective potentials but face the problem in respect of stability, solubility, and bioavailability. The BBB prevents the crossing of the compounds and hereby hinders their movement from blood to the brain. However, nanotechnology and nanocarriers can play an important role in their bioavailability enhancement. Natural products when entrapped in nanocarriers can increase the bioavailability and stability of the products. Various types of nanocarriers like nanogels, nanoparticles, emulgel, nanosuspension, self-micro emulsifying drug delivery systems, nanostructured lipid carriers, and Nano micelles can be prepared for the delivery of phytoconstituents. A number of studies have been published in the literature in which nanocarriers have been used for the entrapment of phytoconstituents and they significantly enhanced their stabilization and solubilization [65-68].

CONCLUSION

The therapeutic potential of phytoconstituents to act as neuroprotective has been supported by a vast number of literature. Natural compounds are well known for their bioactivities such as reactive oxygen scavenging activity, antioxidant action, antiproliferative action, antimicrobial, anticancer, and neuroprotective actions. Various compounds such as luteolin, hesperidin, resveratrol, genistein, and many other compounds are there which are much more effective against neurodegeneration. However, their actions are limited due to their solubility, stability, and therapeutic efficacy-related problems. It was envisaged from the published data that the therapeutic action of the natural compounds can be enhanced by incorporating the phytoconstituents in the nanocarriers such as nanoparticles, nanogels, and nanostructured lipid carriers. They can enhance the stability and specificity of the bioactive compounds to a larger extent. The use of nanotechnology can also provide targeting which enhances their specificity to the respective site of action.

LIST OF ABBREVIATIONS

ALS

Amyotrophic Lateral Sclerosis

AM

Astragalus membranaceus

BBB

Blood-brain Barrier

LPO

Lipid Peroxidase

MAO

Monoamine Oxidase

MM

Marine Macroalgae

NDs

Neurodegenerative Disorders

OS

Oxidative Stress

ROS

Reactive Oxygen Species

CONSENT FOR PUBLICATION

Not applicable.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.