Management Of Neurological Disorders Research Articles

CSF neopterin, quinolinic acid and kynurenine/tryptophan ratio are biomarkers of active neuroinflammation

Defining the presence of acute and chronic brain inflammation remains a challenge to clinicians due to the heterogeneity of clinical presentations and aetiologies. However, defining the presence of neuroinflammation, and monitoring the effects of therapy is important given its reversible and potentially damaging nature. We investigated the utility of CSF metabolites in the diagnosis of primary neuroinflammatory disorders such as encephalitis and explored the potential pathogenic role of inflammation in epilepsy. Cerebrospinal fluid (CSF) collected from 341 paediatric patients (169 males, median age 5.8 years, range 0.1-17.1) were examined. The patients were separated into a primary inflammatory disorder group (n=90) and epilepsy group (n=80), who were compared with three control groups including neurogenetic and structural (n=76), neurodevelopmental disorders, psychiatric and functional neurological disorders (n=63), and headache (n=32). There were statistically significant increases of CSF neopterin, kynurenine, quinolinic acid and kynurenine/tryptophan ratio (KYN/TRP) in the inflammation group compared to all control groups (all p<0.0003). As biomarkers, at thresholds with 95% specificity, CSF neopterin had the best sensitivity for defining neuroinflammation (82%, CI 73-89), then quinolinic acid (57%, CI 47-67), KYN/TRP ratio (47%, CI 36-56) and kynurenine (37%, CI 28-48). CSF pleocytosis had sensitivity of 53%, CI 42-64). The area under the receiver operating characteristic curve (ROC AUC) of CSF neopterin (94.4% CI 91.0-97.7%) was superior to that of CSF pleocytosis (84.9% CI 79.5-90.4%) (p=0.005). CSF kynurenic acid/kynurenine ratio (KYNA/KYN) was statistically decreased in the epilepsy group compared to all control groups (all p≤0.0003), which was evident in most epilepsy subgroups. Here we show that CSF neopterin, kynurenine, quinolinic acid and KYN/TRP are useful diagnostic and monitoring biomarkers of neuroinflammation. These findings provide biological insights into the role of inflammatory metabolism in neurological disorders and provide diagnostic and therapeutic opportunities for improved management of neurological diseases. Financial support for the study was granted by Dale NHMRC Investigator grant APP1193648, University of Sydney, Petre Foundation, Cerebral Palsy Alliance and Department of Biochemistry at the Children's Hospital at Westmead. Prof Guillemin is funded by NHMRC Investigator grant APP 1176660 and Macquarie University.

Exploring the Therapeutic Potential of the Ketogenic Diet on Neurological Disorders: A Comprehensive Review

The ketogenic diet (KD) has emerged as a promising therapeutic strategy for a variety of neurological disorders, including epilepsy, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and autism spectrum disorder. The potential benefits of the KD are attributed to its capacity to modulate neurotransmission, reduce inflammation, improve mitochondrial function, and enhance synaptic plasticity. Despite the growing body of evidence supporting the KD's therapeutic potential, there remain challenges in its implementation, such as potential side effects, nutrient deficiencies, and the need for careful monitoring by healthcare professionals. Factors affecting the success of the KD include patient adherence, individual metabolic response, and appropriate diet customization. This review summarizes the current evidence supporting the KD's role in the management of neurological disorders, discusses the underlying mechanisms of action, highlights the challenges and considerations associated with its use, and addresses the factors that can influence treatment success. Further research is needed to optimize the KD for different patient populations, elucidate the specific therapeutic mechanisms, and identify potential biomarkers to predict treatment response, ultimately enhancing the quality of life and overall well-being of individuals affected by neurological disorders.

The Interplay Between the Gut Microbiome and Neurological Disorders: Exploring the Gut-Brain Axis

The gut-brain axis is a complex communication system between the gut and the brain that has a significant impact on overall health and well-being. Recent evidence suggests that the gut microbiome plays a critical role in this communication system, and that imbalances in the gut microbiome can contribute to the development and progression of neurological disorders. In this comprehensive review, we provide an overview of the gut-brain axis, including the structure and function of the gut microbiome, and the various gut-brain communication pathways. We also discuss the role of dysbiosis, or imbalances in the gut microbiome, in the development and progression of neurological disorders, and the various gut-directed therapies that have been shown to be effective in these conditions, including probiotics, prebiotics, and fecal microbiota transplantation. Finally, we discuss the future directions and challenges in gut-brain research for neurological disorders, including the need for standardized and validated methods for measuring gut microbiome composition and function, and the complex and multi-factorial nature of the gut-brain axis. This review provides a comprehensive overview of the current state of the field and highlights the importance of the gut-brain axis in the management of neurological disorders.

Implementation of Exome Sequencing in Clinical Practice for Neurological Disorders.

Neurological disorders (ND) are diseases that affect the brain and the central and autonomic nervous systems, such as neurodevelopmental disorders, cerebellar ataxias, Parkinson's disease, or epilepsies. Nowadays, recommendations of the American College of Medical Genetics and Genomics strongly recommend applying next generation sequencing (NGS) as a first-line test in patients with these disorders. Whole exome sequencing (WES) is widely regarded as the current technology of choice for diagnosing monogenic ND. The introduction of NGS allows for rapid and inexpensive large-scale genomic analysis and has led to enormous progress in deciphering monogenic forms of various genetic diseases. The simultaneous analysis of several potentially mutated genes improves the diagnostic process, making it faster and more efficient. The main aim of this report is to discuss the impact and advantages of the implementation of WES into the clinical diagnosis and management of ND. Therefore, we have performed a retrospective evaluation of WES application in 209 cases referred to the Department of Biochemistry and Molecular Genetics of the Hospital Clinic of Barcelona for WES sequencing derived from neurologists or clinical geneticists. In addition, we have further discussed some important facts regarding classification criteria for pathogenicity of rare variants, variants of unknown significance, deleterious variants, different clinical phenotypes, or frequency of actionable secondary findings. Different studies have shown that WES implementation establish diagnostic rate around 32% in ND and the continuous molecular diagnosis is essential to solve the remaining cases.

A Systematic Review of Neurological Complications in Pregnant Women With COVID-19.

Coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2), has killed millions of people around the world so far and has turned into a disaster for people and healthcare systems. Neurological problems are often seen in people with COVID-19 in the general population, but it is unclear how common they are in pregnant women. This study provides a summary of studies on pregnant women with proven SARS-CoV-2 infection and a particular neurologic diagnosis from different parts of the world. After applying the inclusion and exclusion criteria, a total of 15 papers were assessed to create this review article. Based on our findings, the peripheral and central nervous systems were both equally impacted: Guillain-Barré syndrome (GBS, n=1), bifacial weakness, paresthesia, and vestibulocochlear neuritis (n=1), eclampsia types (n=2), and neurological disease (n=2); case reports, retrospective studies, editorials, and prospective observational studies were included. The median gestational age was 34 (30-36.5) weeks, and the median maternal age was 32.5 (25-35) years. Given the number of reports of neurologic problems associated with COVID-19 in the general community, our findings might be overstated, and we chose the ones that fit our criteria. We hope that this review helps in the early detection and management of neurological diseases during pregnancy.

Metal-Organic Frameworks-Based Nanoplatforms for the Theranostic Applications of Neurological Diseases.

Neurological diseases are the foremost cause of disability and the second leading cause of death worldwide. Owing to the special microenvironment of neural tissues and biological characteristics of neural cells, a considerable number of neurological disorders are currently incurable. In the past few years, the development of nanoplatforms based on metal-organic frameworks (MOFs) has broadened opportunities for offering sensitive diagnosis/monitoring and effective therapy of neurology-related diseases. In this article, the obstacles for neurotherapeutics, including delayed diagnosis and misdiagnosis, the existence of blood brain barrier (BBB), off-target treatment, irrepressible inflammatory storm/oxidative stress, and irreversible nerve cell death are summarized. Correspondingly, MOFs-based diagnostic/monitoring strategies such as neuroimaging and biosensors (electrochemistry, fluorometry, colorimetry, electrochemiluminescence, etc.) and MOFs-based therapeutic strategies including higher BBB permeability, targeting specific lesion sites, attenuation of neuroinflammation/oxidative stress as well as regeneration of nerve cells, are extensively highlighted for the management of neurological diseases. Finally, the challenges of the present research from perspective of clinical translation are discussed, hoping to facilitate interdisciplinary studies at the intersections between MOFs-based nanoplatforms and neurotheranostics.

Bifidobacterium breve Bif11 supplementation improves depression-related neurobehavioural and neuroinflammatory changes in the mouse

Gut dysbiosis has been closely linked to the onset and progression of several brain-related disorders such as depression. The administration of microbiota-based formulations such as probiotics helps restore healthy gut flora and plays a role in preventing and treating depression-like behavior. Therefore, we evaluated the efficacy of probiotic supplementation using our recently isolated putative probiotic Bifidobacterium breve Bif11 in ameliorating lipopolysaccharide (LPS)-induced depression-like behavior in male Swiss albino mice. Mice were fed orally with B. breve Bif11 (1 × 1010 CFU and 2 × 1010 CFU) for 21 days before being challenged with a single intraperitoneal LPS injection (0.83 mg/kg). Behavioral, biochemical, histological and molecular analysis were done with an emphasis on inflammatory pathways linked to depression-like behavior. Daily supplementation with B. breve Bif11 for 21 days prevented the onset of depression-like behavior induced by LPS injection, besides reducing the levels of inflammatory cytokines such as matrix metalloproteinase-2, c-reactive protein, interleukin-6, tumor necrosis factor-alpha and nuclear factor kappa-light-chain-enhancer of activated B cells. It also prevented the decrease of the brain-derived neurotrophic factor levels and neuronal cell viability in the prefrontal cortex of LPS-treated mice. Furthermore, we observed that gut permeability was reduced, there was an improved short-chain fatty acid profile and reduced gut dysbiosis in the LPS mice fed with B. breve Bif11. Similarly, we observed a decrease in behavioural deficits and restoration of gut permeability in chronic mild stress. Together, these results would help in deciphering the role of probiotics in the management of neurological disorders where depression, anxiety and inflammation are prominent clinical features.This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".

Nanomedicine based strategies for oligonucleotide traversion across the blood-brain barrier.

Neurological disorders are considered the most prominent cause of disability worldwide. The major hurdle in the management of neurological disorders is the existence of the blood-brain barrier (BBB), which hinders the entry of several therapeutic moieties. In recent years, oligonucleotides have gained tremendous attention for their target specificity, diminished dose and adverse effects, thereby halting disease progression. However, enzymatic degradation, rapid clearance, limited circulation and availability at the bio-active site, etc., limit its clinical translation. Nanomedicine has opened up a breadth of opportunities in the delivery of oligonucleotides across the BBB. This review addresses the pitfalls associated with oligonucleotide delivery in traversing the BBB via nanotherapeutics for the management of brain disorders. Regulatory perspectives pertaining to hastening the clinical translation of oligonucleotide-loaded nanocarriers for brain delivery have been highlighted.

Transcriptional and epigenetic regulation of microglia in maintenance of brain homeostasis and neurodegeneration.

The emerging role of microglia in brain homeostasis, neurodegeneration, and neurodevelopmental disorders has attracted considerable interest. In addition, recent developments in microglial functions and associated pathways have shed new light on their fundamental role in the immunological surveillance of the brain. Understanding the interconnections between microglia, neurons, and non-neuronal cells have opened up additional avenues for research in this evolving field. Furthermore, the study of microglia at the transcriptional and epigenetic levels has enhanced our knowledge of these native brain immune cells. Moreover, exploring various facets of microglia biology will facilitate the early detection, treatment, and management of neurological disorders. Consequently, the present review aimed to provide comprehensive insight on microglia biology and its influence on brain development, homeostasis, management of disease, and highlights microglia as potential therapeutic targets in neurodegenerative and neurodevelopmental diseases.

Cognitive enhancing properties of aqueous leaf extract of Vigna unguiculata in ketamine-induced memory damage in mice

Conventional remedies for management of Alzheimer’s disease (AD) and related cognitive deficits are not curative but relieves the symptoms and they cause adverse side effects. Alternatively, use of herbal therapies to manage cognitive illnesses has increased substantially. Vigna unguiculata is commonly utilized for nutritional benefits and management of neurological disorders in herbal medicine. The present study evaluated cognitive enhancing potential of V. unguiculata leaf aqueous extract in mice with ketamine-induced AD-like cognitive deficits. Cognitive performance indicated by step-through latency was assessed using passive avoidance test. Anti-acetylcholinesterase (anti-AChE) and antioxidant potential of the extract was assessed using brains of the test animals. Further, phytochemical constituents of the extracts were determined using LC-MS. Aqueous extract of V. unguiculata leaf demonstrated significant prowess to combat cognitive deficits in the test animals. This was evidenced by significantly higher (p &lt; 0.001) step-through latencies in extract-treated mice than the untreated cognitively damaged mice. Moreover, cognitively damaged mice given the studied extract exhibited significantly less (p &lt; 0.001) malondialdehyde levels and acetylcholinesterase activity than the negative control mice. This result confirmed antioxidant and anti-AChE properties of V. unguiculata, indicating its potential to attenuate oxidative stress in the brain and augment cholinergic transmission. Notably, some conventional therapies for cognitive disorders especially AD are AChE inhibitors. The studied extract contained phytocompounds such as flavonoids and phenolics with confirmed antioxidant and anti-AChE activities, thus, its cognitive enhancing efficacy could be attributed to these phytoconstituents. Collectively, this study upholds V. ungiculata usefulness in management of cognitive illnesses.

The concept and practical management of frailty in neurology

Frailty is a clinical situation of decreased homeostatic reserve that, after a minor trigger (acute illness, fall, taking a drug...) increases the risk of an adverse event such as hospital admission, institutionalization, functional and/or cognitive decline, death, etc. Frailty can be understood as physical frailty, Fried's phenotype, a true geriatric syndrome that can be reversible by avoiding its progression to more advanced stages of irreversibility and dependence, and Rockwood's frailty due to accumulation of deficits, as a continuum of health or classification typology of the elderly along the frailty spectrum (healthy, robust, vulnerable, mild-moderate-severe and extreme frailty or end of life). The diagnosis of physical frailty is part of the comprehensive geriatric assessment, recommending the use of a performance test such as gait speed (<0,8m/s), Timed Up and Go (>12 s) or Short Physical Performance Battery (<10). Physical frailty is reversible by a multidisciplinary management based on three fundamental pillars: multicomponent physical exercise and resistance training, adequate protein and micronutrient intake (leucine, vitamin D, etc.) and appropriate pharmacological prescription, management of comorbidity and geriatric syndromes. Frailty is a risk factor for neurological disease progression and increased risk of adverse events in neurodegenerative diseases such as mild cognitive impairment, dementia, Parkinson's disease and cerebrovascular disease. Frailty based on the Clinical Frailty Scale or VIG-Frail shows patient typologies in relation to a greater or lesser state of fragility, being a basic prognostic tool of great utility in making diagnostic and therapeutic management decisions. It opens up a new opportunity for improvement in the management of neurological disease in the diagnosis and treatment of frailty.

Adapting patient treatment of neurological diseases during the COVID-19 pandemic

&lt;abstract&gt; &lt;p&gt;Treating neurological patients during the pandemic period has become extremely challenging. At the same time, responding properly to these challenges has been diverse around the world, with varying levels of readiness, discipline, and approach. Additionally, there are significant differences in healthcare resources and processes between nations, and even within a nation, and these have significantly influenced the treatment procedure throughout the pandemic. However, neurologists have been called to care for patients with neurological symptoms who have COVID-19, and to continue managing COVID-19-affected neurological comorbidities in patients as before. This study highlights how the treatment procedures for neurological diseases are rapidly changing due to the spread of the SARS-CoV-2 virus. It also focuses on the challenges healthcare professionals are facing while providing proper treatment to neurological patients during the pandemic situation. Lastly, it offers some useful recommendations regarding the effective management of neurological diseases during the COVID-19 pandemic period.&lt;/p&gt; &lt;/abstract&gt;

MORPHOMETRIC STUDY OF THE FRONTAL HORN OF LATERAL VENTRICLES OF BRAIN BY IMAGING USING COMPUTERIZED TOMOGRAPHY

Introduction The cerebral ventricular system consists of a series of interconnecting spaces and channels which originate from the central lumen of the embryonic neural tube. The ventricular system lled with cerebrospinal uid, is an essential part of the brain. Understanding the normal anatomy and the variations of the ventricular system of brain is helpful for clinicians, neurosurgeons and radiologists in day-to-day clinical practice1. Aims And Objectives To determine the average dimensions and variations of the frontal horn of the normal lateral ventricles of brain by CT scan. Materials And Methods The study was conducted in individuals who attended the Department of Radiodiagnosis in Government Medical College, Thiruvananthapuram. Those patients whose brain CT scans were read as normal by the radiologist were taken up for the study. A total of 200 CT brain of individuals above 10 years of age were taken during the period from January 2017 to June 2018.100 males and 100 females were included in the study group. Results The length of the frontal horn of lateral ventricle of brain was found to be more on the left side and in male gender. It was also observed to be increasing with age. Conclusion The present study outlines the normal values of the length of frontal horn of the lateral ventricles of brain using Computerized tomography which would aid in the diagnosis and management of neurological disorders.

Deep Tissue Penetration of Bottle-Brush Polymers via Cell Capture Evasion and Fast Diffusion

Drug nanocarriers (NCs) capable of crossing the vascular endothelium and deeply penetrating into dense tissues of the CNS could potentially transform the management of neurological diseases. In the present study, we investigated the interaction of bottle-brush (BB) polymers with different biological barriers in vitro and in vivo and compared it to nanospheres of similar composition. In vitro internalization and permeability assays revealed that BB polymers are not internalized by brain-associated cell lines and translocate much faster across a blood-brain barrier model compared to nanospheres of similar hydrodynamic diameter. These observations performed under static, no-flow conditions were complemented by dynamic assays performed in microvessel arrays on chip and confirmed that BB polymers can escape the vasculature compartment via a paracellular route. BB polymers injected in mice and zebrafish larvae exhibit higher penetration in brain tissues and faster extravasation of microvessels located in the brain compared to nanospheres of similar sizes. The superior diffusivity of BBs in extracellular matrix-like gels combined with their ability to efficiently cross endothelial barriers via a paracellular route position them as promising drug carriers to translocate across the blood-brain barrier and penetrate dense tissue such as the brain, two unmet challenges and ultimate frontiers in nanomedicine.

PP77 Safety, Effectiveness, And Cost Effectiveness Of Telemedicine In Neurological Diseases

IntroductionTelemedicine has been introduced in health services, but uncertainties about the real value of this strategy in the management of neurological diseases remain.MethodsA systematic review was undertaken of available scientific literature on the safety, effectiveness, and cost effectiveness of telemedicine combined with in-person visits, compared with usual care, for the treatment and follow-up assessment of patients with neurological diseases. The overall effect size for each neurological disease was estimated using meta-analysis. An economic analysis was performed from the societal and Spanish healthcare system perspectives.ResultsTwo economic studies were included for cost effectiveness and 25 randomized controlled trails (n=8,976 patients) were included for the effectiveness and safety assessment (11 on cerebrovascular diseases, four on Parkinson’s disease, three on multiple sclerosis, two on epilepsy, and one each on brain damage, dementia, spina bifida, migraine, and cerebral palsy). The types of telemedicine evaluated included: virtual visits (11 studies); telerehabilitation (seven studies); telephone calls (three studies); smartphone apps (two studies); and online software for computers (two studies). Subgroup analysis by type of telemedicine indicated no discernible effect for telemedicine combined with in-person visits on most of the outcomes analyzed for the various neurological diseases. Given the heterogeneity of diseases, types of telemedicine, and the results observed, a cost-minimization analysis was conducted. Combining telemedicine with in-person visits would cost EUR 2.55 per patient from the perspective of the healthcare system, but it would result in cost savings (EUR 27.34 per patient) from the societal perspective.ConclusionsThe safety and effectiveness of combining in-person visits with telemedicine was similar to that of usual care, but it could be a cost-saving strategy in Spain from a societal perspective.

Role of Probiotics and Diet in the Management of Neurological Diseases and Mood States: A Review.

Alzheimer's (AD) and Parkinson's diseases (PD) are common in older people. Autism spectrum disorders (ASD), anxiety, depression, stress, and cognitive impairment are prevalent among people irrespective of age. The incidence of neurological disorders has been increasing in recent decades. Communication between the gut microbiota and the brain is intrinsically complicated, and it is necessary for the maintenance of the gut, brain, and immune functions of the host. The bidirectional link among the gut, gut microbiota and the brain is designated as the "microbiota-gut-brain axis." Gut microbiota modulates the host immune system and functions of tissue barriers such as gut mucosa and blood-brain barrier (BBB). Gut microbial dysfunction disturbs the gut-brain interplay and may contribute to various gut disorders, neurocognitive and psychiatric disorders. Probiotics could protect intestinal integrity, enhance gut functions, promote intestinal mucosal and BBB functions, and support the synthesis of brain-derived neurotrophic factors, which enhance neuronal survival and differentiation. Probiotics could be considered an adjunct therapy to manage metabolic and psychiatric diseases. Predominantly, Lactobacillus and Bifidobacterium strains are documented as potent probiotics, which help to maintain the bidirectional interactions between the gut and brain. The consumption of probiotics and probiotics containing fermented foods could improve the gut microbiota. The diet impacts gut microbiota, and a balanced diet could maintain the integrity of gut-brain communication by facilitating the production of neurotrophic factors and other neuropeptides. However, the beneficial effects of probiotics and diet might depend upon several factors, including strain, dosage, duration, age, host physiology, etc. This review summarizes the importance and involvement of probiotics and diet in neuroprotection and managing representative neurological disorders, injuries and mood states.

Advanced therapeutic strategies targeting microglia: beyond neuroinflammation.

For a long time, microglia have been recognized as the main culprits of neuroinflammatory responses because they are primary phagocytes present in the parenchyma of the central nervous system (CNS). However, with the evolving concept of microglial biology, advanced and precise approaches, rather than the global inhibition of activated microglia, have been proposed in the management of neurological disorders. Yolk sac-derived resident microglia have heterogeneous composition according to brain region, sex, and diseases. They play a key role in the maintenance of CNS homeostasis and as primary phagocytes. The perturbation of microglia development can induce neurodevelopmental disorders. Microglia aggravate or alleviate neuroinflammation according to microenvironment and their spatiotemporal dynamics. They are long-lived cells and repopulate via their proliferation or external monocyte engraft. Based on this evolving concept, understanding advanced therapeutic strategies targeting microglia can give us an opportunity to discover novel therapies for neurological disorders.

Neuromodulatory effect of plant metabolites

Neurological disorders (NDDs) are diseases that affect the central and peripheral nervous systems. Gradual malfunction and destruction of the neurons or the nerve cells characterize them. Every year, NDDs affect millions of people worldwide. Over the years, several neuromodulatory techniques have been introduced to improve the quality of life for those affected by NDDs. NDDs are chronic and incurable conditions, however, bioactive substances derived from medicinal plants have emerged as the greatest choice for their prevention and treatment. Literature evidences several benefits of plant metabolites as alternative medicines for the prevention and treatment of NDDs. Numerous investigations have shown plant metabolites to possess beneficial biological effects because of their qualities, which include but are not limited to anti-inflammatory, antioxidant, and neuroprotective actions. Practices of folk medicine and several studies have also guided many phytopharmacological interventions toward the treatment of NDDs. This review aims to highlight secondary metabolites (alkaloids, flavonoids, steroids, terpenoids) of plants with neuroprotective action that could potentially play an important role in the prevention and management of NDDs.

Dietary supplements in neurological diseases and brain aging.

A healthy diet shapes a healthy mind. Diet quality has a strong association with brain health. Diet influences the onset and consequences of neurological diseases, and dietary factors may influence mental health at individual and population level. The link between unhealthy diet, impaired cognitive function and neurodegenerative diseases indicates that adopting a healthy diet would ultimately afford prevention and management of neurological diseases and brain aging. Neurodegenerative diseases are of multifactorial origin and result in progressive loss of neuronal function in the brain, leading to cognitive impairment and motoneuron disorders. The so-called Mediterranean diet (MedDiet) with its healthy ingredients rich in antioxidant, anti-inflammatory, immune, neuroprotective, antidepressant, antistress and senolytic activity plays an essential role in the prevention and management of neurological diseases and inhibits cognitive decline in neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. The MedDiet also modulates the gut-brain axis by promoting a diversity of gut microbiota. In view of the importance of diet in neurological diseases management, this review focuses on the dietary components, natural compounds and medicinal plants that have proven beneficial in neurological diseases and for brain health. Among them, polyphenols, omega-3 fatty acids, B vitamins and several ayurvedic herbs have promising beneficial effects.

In‐Vitro Antioxidant Assays and Computational Investigation of Phytoconstituents from Theobroma cacao Beans as Inhibitors of Neuro‐Modulatory Enzymes

Neurodegenerative disease (ND) is a heterogeneous group of disorders characterized by progressive deterioration of neuronal cells in the nervous system. Also, there are an increasing number of neurodegenerative disease cases as the number of elderly people increases. Biochemical and molecular investigations have shown that ND pathogenesis is strongly associated with pathologically misfolded proteins. Therefore, blocking altered proteins/therapeutic targets by small molecules may help in the management of neurological disorders such as Alzheimer’s disease and Parkinson’s disease. As such, this study was carried out to evaluate the pharmacological potential of aqueous extract from the medicinal plant, Theobroma cacao, from which bioactive compounds were identified with the potential to inhibit Arginase II and Monoamine Oxidase B (MAO‐B). Chemical profiling and characterization of T. cacao using High‐Performance‐Liquid‐Chromatography reveal the presence of catechin, p‐coumaric acid, epicatechin, gallic acid, caffeic acid, kaempferol, and ellagic acid as the common compounds in the Amazon and Amelonado type of T. cacao. The total phenolic content in Amelonado and Amazon were 1.420 mg and 0.270 mg GAE/g extract, respectively. Flavonoid content was 0.460 mg in Amelonado and 0.720 mg in Amazon. Antioxidant activity of the plant via DPPH radical scavenging effect shows T. cacao has 49.330% in Amelonado and 42.490% in Amazon. The high degree of radical scavenging effect of T. cacao was relatively the same in Amelonado and Amazon, which may be attributed to their high phenolic contents. To further establish the molecular mechanism of T. cacao antioxidant property and inhibitory mechanism against Argainse II and MAO‐B. Computational techniques incorporating molecular docking, pharmacokinetics models, and molecular dynamics simulation were employed. The molecular docking results showed anti‐neurodegenerative potential with Epicatechin showing the highest inhibition against MAO‐B with a docking score of ‐11.156 kcal/mol and kaempferol inhibiting Arginase II with a docking score of ‐7.002 kcal/mol. The lead complexes (epicatechin‐MAOB and Kaempferol‐Arginase II) were subject to MD simulation for a period of 100 ns for stability analysis. The stability shows the compounds established molecular interactions and were found to be stable. The pharmacokinetics model reveals the compound are promising therapeutic agents. Overall, bioactive compounds from T. cacao may be ideal phyto‐drugs in the management of neurological disorders.