Neuronal Differentiation and Outgrowth Effect of Thymol in Trachyspermum ammi Seed Extract via BDNF/TrkB Signaling Pathway in Prenatal Maternal Supplementation and Primary Hippocampal Culture.

Reviving the neuronal functions in neurodegenerative disorders requires the promotion of neurite outgrowth. Thymol, which is a principal component of Trachyspermum ammi seed extract (TASE), is reported to have neuroprotective effects. However, the effects of thymol and TASE on neuronal differentiation and outgrowth are yet to be studied. This study is the first report investigating the neuronal growth and maturation effects of TASE and thymol. Pregnant mice were orally supplemented with TASE (250 and 500 mg/kg), thymol (50 and 100 mg/kg), vehicle, and positive controls. The supplementation significantly upregulated the expression of brain-derived neurotrophic factor (BDNF) and early neuritogenesis markers in the pups' brains at post-natal day 1 (P1). Similarly, the BDNF level was significantly upregulated in the P12 pups' brains. Furthermore, TASE (75 and 100 µg/mL) and thymol (10 and 20 µM) enhanced the neuronal polarity, early neurite arborization, and maturation of hippocampal neurons in a dose-dependent manner in primary hippocampal cultures. The stimulatory activities of TASE and thymol on neurite extension involved TrkB signaling, as evidenced by attenuation via ANA-12 (5 µM), which is a specific TrkB inhibitor. Moreover, TASE and thymol rescued the nocodazole-induced blunted neurite extension in primary hippocampal cultures, suggesting their role as a potent microtubule stabilizing agent. These findings demonstrate the potent capacities of TASE and thymol in promoting neuronal development and reconstruction of neuronal circuitry, which are often compromised in neurodegenerative diseases and acute brain injuries.

Thymol in Trachyspermum ammi seed extract exhibits neuroprotection, learning, and memory enhancement in scopolamine-induced Alzheimer's disease mouse model.

Several reports have stated the neuroprotective and learning/memory effects of Tachyspermum ammi seed extract (TASE) and its principal component thymol; however, little is known about its underlying molecular mechanisms and neurogenesis potential. This study aimed to provide insights into TASE and a thymol-mediated multifactorial therapeutic approach in a scopolamine-induced Alzheimer's disease (AD) mouse model. TASE and thymol supplementation significantly reduced oxidative stress markers such as brain glutathione, hydrogen peroxide, and malondialdehyde in mouse whole brain homogenates. Tumor necrosis factor-alpha was significantly downregulated, whereas the elevation of brain-derived neurotrophic factor and phospho-glycogen synthase kinase-3 beta (serine 9) enhanced learning and memory in the TASE- and thymol-treated groups. A significant reduction in the accumulation of Aß 1-42 peptides was observed in the brains of TASE- and thymol-treated mice. Furthermore, TASE and thymol significantly promoted adult neurogenesis, with increased doublecortin positive neurons in the subgranular and polymorphic zones of the dentate gyrus in treated-mice. Collectively, TASE and thymol could  potentially act as natural therapeutic agents for the treatment of  neurodegenerative disorders, such as  AD.

Changes in the economic value of ecosystem services in rapidly growing urban areas: the case of Dhaka, Bangladesh.

Assessing the effects of land use patterns on ecosystem services can provide a conceptual foundation and point of reference for spatial planning strategies. The benefits ecosystems bring to individuals' lives and general well-being are referred to as ecosystem services. Land use/land cover (LULC) could influence various ecosystems and have implications for natural habitats and the quality of life. LULC has changed dramatically in Bangladesh during the past few decades, notably in the Dhaka Metropolitan Area. However, no attempt has been made to examine the co-evolution of LULC variations and values of ecosystem services (ESV) in the Dhaka Metropolitan Area. The study's objective is to evaluate the impact of LULC changes and different socio-demographic factors on ESV. LULC data sets were extracted from Landsat OLI and TIRS images using maximum likelihood classification. Analyses were conducted on both ESV estimations and driving forces, and the influence of LULC dynamics on the ESV was assessed. Data from 1991, 2001, 2011, and 2021 were used to estimate ESVs. LULC in the major metropolitan area of Dhaka has seen considerable changes between 1991 and 2021, with the most important change being the declination of water bodies, vegetation, and agricultural land. Vegetation and agricultural land proportions dropped from 22.50% and 19.29%, respectively, to 6.45% and 10.60%. Overall, there was a US$25.11M drop in ESV during 1991-2021. The study emphasizes the value of integrated land use planning for tightly regulating and controlling the growth of built-up regions. This will be essential for maintaining ecological sustainability and contributing to ecosystem resilience.

Analyzing the spatio-temporal directions of air pollutants for the initial wave of Covid-19 epidemic over Bangladesh: Application of satellite imageries and Google Earth Engine.

One of the most critical issues for city viability and global health is air quality. The shutdown interval for the COVID-19 outbreaks has turned into an ecological experiment, allowing researchers to explore the influence of human/industrial operations on air quality. In this study, we have observed and examined the spatial pattern of air pollutants, specifically CO, NO2, SO2, O3 as well as AOD Over Bangladesh. For that reason, the timeline was chosen from March 2019 to October 2020 (before and during the first surge of COVID-19). The full analysis has been performed in Google Earth Engine (GEE). The findings showed that, CO, SO2, and AOD levels dropped significantly, but SO2 dropped slowly and O3 levels were similar, with marginally greater quantities in some areas during the lockdown than in 2019. During the shutdown, the association involving airborne pollutants and weather parameters (temperature and rainfall) revealed that rainfall and temperature were directly associated with air pollutants. COVID-19 mortality had a high positive connection with NO2 (R2 = 0.145; r = 0.38) and AOD (R2 = 0.17; r = 0.412). It is also found that various air impurities concentration has a strong relationship with Covid death. It would help the policymakers and officials to gain a better understanding of the sources of atmospheric emissions to develop a substantial proof of short- and long-term mitigation ways to enhance air quality and reduce the associated disease and disability burden.

Nutritional profiling of some selected commercially important freshwater and marine water fishes of Bangladesh.

The purpose of the study was to investigate the proximate composition and mineral content of Bangladesh's economically important freshwater and marine water fish. Proximate composition and mineral content was determined according to the Association of Official Agricultural Chemists (AOAC) standard method. All of the factors had a substantial variation (p < 0.05), according to the findings. The maximum protein content was observed in Lates calcarifer (18.673%) and minimum in Pangasius pangasius (15.616%). The content of lipid among the species varied from 0.316% to 13.396%, with Mugil cephalus having the highest lipid content and Channa striata having the lowest. The moisture content ranges from 68.343% to 81.160%. All the fishes have an average ash content of 0.850%-4.350%. The energy content is also significantly higher in marine water fishes. The mineral content was highly variable. Calcium content was lowest in Pangasius pangasius (0.555%) and highest in Setipinna phasa (3.495%). The magnesium content ranged between 0.281% and 1.885%. Phosphorus was lowest in Lepturacanthus savala (0.826%) and highest in Setipinna phasa (2.114%). The amount of sodium, potassium, and sulfur was relatively less for all fish species but there were substantial differences across the twelve samples. The PCA biplot's for proximate composition analyses has demonstrated positive affinity only between Lates calcarifer and Mugil cephalus in case of ash, lipid, and carbohydrate whereas Setipina phasa, Mugil cephalus, Lutjanus lutjanus, and Oreochromis mossambicus were grouped together with magnesium, phosphorus, calcium, and sulfur in the case of mineral content. Overall, the marine water fishes can be a good food item in terms of nutrition which could provide better health benefits for human.

Assessing the bridge construction effect on river shifting characteristics through geo-spatial lens: A case study on Dharla River, Bangladesh.

The key objective of the bridge structure on a river is to confirm and assist the continual communication. On the other hand, it also has a harmful effect on the hydrological and morphological behavior of the neighboring zone as of the river width contraction. The present study assessed the Bridge construction effect on river shifting characteristics for Dharla River. For doing so, this study followed two steps. First, Landsat imageries for both pre-bridge structure period (1988, 1993 and 1998) and post-bridge structure period (2003, 2008, 2013 and 2017), has been processed and used to determine the thalweg line. Then, geo-spatial environment has been used to assess the thalweg line shifting characteristics and channel width variations. The results revealed a frequent shifting of thalweg line towards both the east and west direction at the upstream side of this Bridge and also the dominating eastwards shifting at the downstream side of the Bridge. After constructing the Dharla Bridge on Dharla River (i.e. post-bridge structure period) the movement of the channel has been changed at a significant level. Particularly, it has been found that the east side shifting is higher than the west side. Thus, the existing of Dharla Bridge has an abundant effect on the shifting characteristics of thalweg line. The study concluded that the shifting of the thalweg lines of Dharla River undergoes a drastic change of study period and the River can be treated as a very dynamic one. The results of this study might supportive for the sustainable and future development of the rivers and adjacent flood plain in Bangladesh.

The use of Personal Protective Equipment (PPE) and associated environmental challenges: A study on Dhaka, Bangladesh.

The Covid-19 pandemic has caused health crisis and concerns worldwide. The use of Personal Protective Equipment (PPE) has been the primary behavioral and policy response to avert the infection of coronavirus. The emergence of the situation resulted in increased production of PPE, creating a surge in plastic pollution and carbon footprint. The consumption of PPEs is unavoidable; however, proper PPE waste disposal plays a vital role in lessening the associated environmental impacts. This study aims to provide an overview of the environmental challenges associated with Covid-19 pandemic faced in the households located at the heart of Bangladesh, Dhaka City Corporation (DCC) area. The study determines carbon footprint in terms of carbon emission equivalent and plastic pollution potential associated with PPEs. The study further implies that there is a gap in the 3R Strategy implementation in Bangladesh hindering the nation in achieving UN's SDG-12. The findings depict that the proper implementation of the 3R strategy is fundamental for ensuring more a resilient, sustainable and livable environment in the in-pandemic and post-pandemic era and further emphasizes that a strengthened policy framework, operational environmental policy tools, environmental education, and the society and stakeholders' spontaneous response to the plastic pollution challenge are essentially required.

Environmental benefits of blue ecosystem services and residents' willingness to pay in Khulna city, Bangladesh.

Nature-based solutions for urban problems gaining popularity globally. The well-functioning ecosystem could offer a nature-based solution to many urban problems including water, drainage and flooding problems. Therefore, conservation and restoration of urban blue ecosystem components such as pond scape are crucial. This research taking Khulna city of Bangladesh as a case has examined the low-income fringe community's willingness to pay (WTP) for conservation and restoration of pond scape/blue ecosystem service (BES) in their locality from where they benefit. The various types of ecosystem services enjoyed by the local community were identified. To assess the community's WTP for conservation and restoration of pond scape, the payment card approach of the Contingent Valuation Method (CVM) was used. Three environmental attributes were considered to assess the existing condition of the blue ecosystem services in the study area. Findings show that 54% of respondents are not satisfied with the existing conditions of the ecosystem services resulting from the pond scape. Respondent's WTP for eleven types of service facilities was calculated. Results show that only 65.20% are eager to pay an amount of 38 Tk to 138 Tk per month for different service facilities. It means about one-third of the community people want to be free riders. The influences of different attributes of the respondents on their WTP were also analyzed. Education, income, and house-ownership appear to have a positive significant influence on WTP for conservation and restoration of pond scape in the study area. In line with the findings if policy measures are taken without further delay it would help conserve the remaining pond scape.

A Systematic Review on Marine Algae-Derived Fucoxanthin: An Update of Pharmacological Insights.

Fucoxanthin, belonging to the xanthophyll class of carotenoids, is a natural antioxidant pigment of marine algae, including brown macroalgae and diatoms. It represents 10% of the total carotenoids in nature. The plethora of scientific evidence supports the potential benefits of nutraceutical and pharmaceutical uses of fucoxanthin for boosting human health and disease management. Due to its unique chemical structure and action as a single compound with multi-targets of health effects, it has attracted mounting attention from the scientific community, resulting in an escalated number of scientific publications from January 2017 to February 2022. Fucoxanthin has remained the most popular option for anti-cancer and anti-tumor activity, followed by protection against inflammatory, oxidative stress-related, nervous system, obesity, hepatic, diabetic, kidney, cardiac, skin, respiratory and microbial diseases, in a variety of model systems. Despite much pharmacological evidence from in vitro and in vivo findings, fucoxanthin in clinical research is still not satisfactory, because only one clinical study on obesity management was reported in the last five years. Additionally, pharmacokinetics, safety, toxicity, functional stability, and clinical perspective of fucoxanthin are substantially addressed. Nevertheless, fucoxanthin and its derivatives are shown to be safe, non-toxic, and readily available upon administration. This review will provide pharmacological insights into fucoxanthin, underlying the diverse molecular mechanisms of health benefits. However, it requires more activity-oriented translational research in humans before it can be used as a multi-target drug.

Use of relevancy and complementary information for discriminatory gene selection from high-dimensional gene expression data.

With the advent of high-throughput technologies, life sciences are generating a huge amount of varied biomolecular data. Global gene expression profiles provide a snapshot of all the genes that are transcribed in a cell or in a tissue under a particular condition. The high-dimensionality of such gene expression data (i.e., very large number of features/genes analyzed with relatively much less number of samples) makes it difficult to identify the key genes (biomarkers) that are truly attributing to a particular phenotype or condition, (such as cancer), de novo. For identifying the key genes from gene expression data, among the existing literature, mutual information (MI) is one of the most successful criteria. However, the correction of MI for finite sample is not taken into account in this regard. It is also important to incorporate dynamic discretization of genes for more relevant gene selection, although this is not considered in the available methods. Besides, it is usually suggested in current studies to remove redundant genes which is particularly inappropriate for biological data, as a group of genes may connect to each other for downstreaming proteins. Thus, despite being redundant, it is needed to add the genes which provide additional useful information for the disease. Addressing these issues, we proposed Mutual information based Gene Selection method (MGS) for selecting informative genes. Moreover, to rank these selected genes, we extended MGS and propose two ranking methods on the selected genes, such as MGSf-based on frequency and MGSrf-based on Random Forest. The proposed method not only obtained better classification rates on gene expression datasets derived from different gene expression studies compared to recently reported methods but also detected the key genes relevant to pathways with a causal relationship to the disease, which indicate that it will also able to find the responsible genes for an unknown disease data.

Black Cumin (Nigella sativa L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety.

Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin (Nigella sativa L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific community, and pharmaceutical industries. The pleiotropic pharmacological effects of black cumin, and its main bioactive component thymoquinone (TQ), have been manifested by their ability to attenuate oxidative stress and inflammation, and to promote immunity, cell survival, and energy metabolism, which underlie diverse health benefits, including protection against metabolic, cardiovascular, digestive, hepatic, renal, respiratory, reproductive, and neurological disorders, cancer, and so on. Furthermore, black cumin acts as an antidote, mitigating various toxicities and drug-induced side effects. Despite significant advances in pharmacological benefits, this miracle herb and its active components are still far from their clinical application. This review begins with highlighting the research trends in black cumin and revisiting phytochemical profiles. Subsequently, pharmacological attributes and health benefits of black cumin and TQ are critically reviewed. We overview molecular pharmacology to gain insight into the underlying mechanism of health benefits. Issues related to pharmacokinetic herb-drug interactions, drug delivery, and safety are also addressed. Identifying knowledge gaps, our current effort will direct future research to advance potential applications of black cumin and TQ in health and diseases.

Centella asiatica promotes early differentiation, axodendritic maturation and synaptic formation in primary hippocampal neurons.

BACKGROUND: Centella asiatica is a 'medhya-rasayana (nootrophic or memory booster)' herb that has been indicated in Ayurveda for improving memory function and treating dementia disorders. Although the neuroprotective effects of C. asiatica have been reported in earlier studies, the information on whether this nootropic herb could promote early differentiation and development of axon and dendrites in primary hippocampal neurons is currently limited. THE AIM OF THE STUDY: To investigate the effects of C. asiatica and asiatic acid, one of the principal active constituents of C. asiatica, on the various stages of neuronal polarity, including early neuronal differentiation, axonal outgrowth, dendritic arborization, axonal maturation, and synaptic formation. MATERIALS AND METHODS: Embryonic rat hippocampal neurons were incubated with C. asiatica leaf extract (CAE) or asiatic acid. After an indicated time, neurons were fixed and immunolabeled to visualize the neuronal morphology. Morphometric analyses for early neuronal differentiation, axonal and dendritic maturation and synaptogenesis were performed using Image J software. Neuronal viability was determined using trypan blue exclusion assay. RESULTS: CAE at varying concentrations ranging from 3.75 to 15 µg/mL enhanced neurite outgrowth with the highest optimal concentration of 7.5 µg/mL. The effects of CAE commenced immediately after cell seeding, as indicated by its accelerating effect on neuronal differentiation. Subsequently, CAE significantly elaborated dendritic and axonal morphology and facilitated synapse formation. Asiatic acid also facilitated neurite outgrowth, but to a lesser extent than CAE. CONCLUSION: These findings revealed that CAE exerted its modulatory effects in every stage of neuronal development, supporting its previously claimed neurotrophic function and suggest that this natural nootropic and its active component asiatic acid can be further investigated to explore a promising solution for degenerative brain disorders and injuries.

Investigation of mechanisms involved in seed germination enhancement, enzymatic activity and seedling growth of rice (Oryza Sativa L.) using LPDBD (Ar+Air) plasma.

The study investigates the effect of LPDBD (Low Pressure Dielectric Barrier Discharge) (Ar + Air) plasma on seed germination, seedling growth and antioxidant enzyme activity of rice. Rice seeds were treated with LPDBD (Ar + Air) plasma for 2min, 4min, 6min, 8min and 10min. Seed germination rate, seedling growth, total chlorophyll content, enzymatic activity, total soluble sugar and protein concentration were increased in plants grown from the LPDBD (Ar + Air) plasma treated seeds. It was observed that the sprouting of seeds and the growth of seedlings of rice depends on the feed gases used to generate plasma and plasma processing time. In the case of plantlets germinated from the plasma-treated seeds of rice, the H2O2 level was increased significantly both in leaves and roots for 6min, 8min and 10min treatment respectively. No significant change was observed in Nitric Oxide (NO) concentration in seed, leaf, or root of plants grown from LPDBD (Ar + Air) plasma-treated seeds. The amount of total soluble sugar and protein increased significantly in the case of 2min, 4min, 6min, 8min and 10min seed treatment. Although plants exhibited no significant increase in APX activities, but a significant increase of CAT and SOD activity in the leaf and root was found. This study reveals that LPDBD (Ar + Air) plasma is involved in the elevation of ROS species in leaf and root of rice plants which is tightly regulated by the upregulation of CAT activity that ultimately enhances the seed germination and growth of rice plantlets.

The potential LXRß agonist stigmasterol protects against hypoxia/reoxygenation injury by modulating mitophagy in primary hippocampal neurons.

BACKGROUND: Neuronal excitotoxicity induces a plethora of downstream signaling pathways, resulting in the calcium overload-induced excitotoxic cell death, a well-known phenomenon in cerebrovascular and neurodegenerative disorders. The naturally occurring phytosterol, stigmasterol (ST) is known for its potential role in cholesterol homeostasis and neuronal development. However, the ability of ST to protect against the induced excitotoxicity in hippocampal neurons has not been investigated yet. PURPOSE: The present study aimed to investigate whether ST could protect against hypoxia/reoxygenation (H/R)-induced excitotoxicity in hippocampal neurons. METHODS: After H/R, neurons were initially subjected to trypan blue exclusion assay for the assessment of cell viability. Live staining using fluorescence dyes namely JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide), DCFDA (2',7'-dichlorofluorescein diacetate) and FM1-43 (N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) were used to measure MMP, ROS and synaptic vesicle pool size. Immunostaining was performed to analyze the expression levels of vesicular glutamate transporter 1 (VGLUT1), N-methyl-D-acetate receptor subunit 2B (GluN2B), LC3BII, p62, and PTEN induced protein kinase 1 (PINK1) in neuron after H/R. Western blotting was carried out to measure the protein expression of GluN2B. The molecular dynamics simulation was employed to elucidate the LXRß agonistic conformation of ST. RESULT: Pre-incubation of neuronal cultures with ST (20 µM) protected against excitotoxicity, and attenuated reactive oxygen species (ROS) generation, double-stranded DNA break, and mitochondrial membrane potential (MMP) loss. ST treatment also resulted in the downregulation of the expressions of VGLUT1 and GluN2B and the reduction of the size of recyclable synaptic vesicle (SV) pool. Like LXRß agonist GW3695, ST suppressed the expression of GluN2B. Furthermore, ST induced mitophagy through upregulating the expressions of LC3BII, p62, and PINK1. The molecular simulation study showed that ST interacted with the ligand binding domain of liver X receptor ß (LXRß), a known binding receptor of ST, through multiple hydrogen bonding. CONCLUSION: Collectively, these findings revealed that ST exhibited a promising neuroprotective effect by regulating both pre- and post-synaptic events following H/R, particularly, attenuation of GluN2B-mediated excitotoxicity and oxidative stress, and induction of mitophagy, and suggested that ST might be a therapeutic promise against ischemic stroke and its associated neurological disorders.

N-acetyl-D-glucosamine kinase binds dynein light chain roadblock 1 and promotes protein aggregate clearance.

Emerging evidence indicates that neurodegenerative diseases (NDs) result from a failure to clear toxic protein aggregates rather than from their generation. We previously showed N-acetylglucosamine kinase (NAGK) promotes dynein functionality and suggested this might promote aggregate removal and effectively address proteinopathies. Here, we report NAGK interacts with dynein light chain roadblock type 1 (DYNLRB1) and efficiently suppresses mutant huntingtin (mHtt) (Q74) and α-synuclein (α-syn) A53T aggregation in mouse brain cells. A kinase-inactive NAGKD107A also efficiently cleared Q74 aggregates. Yeast two-hybrid selection and in silico protein-protein docking analysis showed the small domain of NAGK (NAGK-DS) binds to the C-terminal of DYNLRB1. Furthermore, a small peptide derived from NAGK-DS interfered with Q74 clearance. We propose binding of NAGK-DS to DYNLRB1 'pushes up' the tail of dynein light chain and confers momentum for inactive phi- to active open-dynein transition.

Integrated System Pharmacology and In Silico Analysis Elucidating Neuropharmacological Actions of Withania somnifera in the Treatment of Alzheimer's Disease.

BACKGROUND: Withania somnifera (WS), also referred to as Medhya Rasayana (nootropic or rejuvenating), has traditionally been prescribed for various neurological ailments, including dementia. Despite substantial evidence, pharmacological roles of WS, neither as nootropic nor as an antidementia agent, are well-understood at the cellular and molecular levels. OBJECTIVES: We aimed at elucidating the pharmacological action mechanisms of WS root constituents against Alzheimer's Disease (AD) pathology. METHODS: Various bioinformatics tools and resources, including DAVID, Cytoscape, NetworkAnalyst and KEGG pathway database were employed to analyze the interaction of WS root bioactive molecules with the protein targets of AD-associated cellular processes. We also used a molecular simulation approach to validate the interaction of compounds with selected protein targets. RESULTS: Network analysis revealed that ß-sitosterol, withaferin A, stigmasterol, withanolide A, and withanolide D are the major constituents of WS root that primarily target the cellular pathways such as PI3K/Akt signaling, neurotrophin signaling and toll-like receptor signaling and proteins such as Tropomyosin receptor Kinase B (TrkB), Glycogen Synthase Kinase-3ß (GSK-3ß), Toll-Like Receptor 2/4 (TLR2/4), and ß-secretase (BACE-1). Also, the in silico analysis further validated the interaction patterns and binding affinity of the major WS compounds, particularly stigmasterol, withanolide A, withanolide D and ß-sitosterol with TrkB, GSK-3ß, TLR2/4, and BACE-1. CONCLUSION: The present findings demonstrate that stigmasterol, withanolide A, withanolide D and ß-sitosterol are the major metabolites that are responsible for the neuropharmacological action of WS root against AD-associated pathobiology, and TrkB, GSK-3ß, TLR2/4, and BACE-1 could be the potential druggable targets.

Neuroprotective Potentials of Marine Algae and Their Bioactive Metabolites: Pharmacological Insights and Therapeutic Advances.

Beyond their significant contribution to the dietary and industrial supplies, marine algae are considered to be a potential source of some unique metabolites with diverse health benefits. The pharmacological properties, such as antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance and anti-amyloidogenic potentials of algal metabolites endorse their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis which are known to be implicated in the pathophysiology of neurodegenerative disorders and the associated complications after cerebral ischemia and brain injuries. As was evident in various preclinical studies, algal compounds conferred neuroprotection against a wide range of neurotoxic stressors, such as oxygen/glucose deprivation, hydrogen peroxide, glutamate, amyloid ß, or 1-methyl-4-phenylpyridinium (MPP+) and, therefore, hold therapeutic promise for brain disorders. While a significant number of algal compounds with promising neuroprotective capacity have been identified over the last decades, a few of them have had access to clinical trials. However, the recent approval of an algal oligosaccharide, sodium oligomannate, for the treatment of Alzheimer's disease enlightened the future of marine algae-based drug discovery. In this review, we briefly outline the pathophysiology of neurodegenerative diseases and brain injuries for identifying the targets of pharmacological intervention, and then review the literature on the neuroprotective potentials of algal compounds along with the underlying pharmacological mechanism, and present an appraisal on the recent therapeutic advances. We also propose a rational strategy to facilitate algal metabolites-based drug development.

Neuroprotection Against Oxidative Stress: Phytochemicals Targeting TrkB Signaling and the Nrf2-ARE Antioxidant System.

Oxidative stress (OS) plays a critical role in the pathophysiology of several brain-related disorders, including neurodegenerative diseases and ischemic stroke, which are the major causes of dementia. The Nrf2-ARE (nuclear factor erythroid 2-related factor 2/antioxidant responsive element antioxidant) system, the primary cellular defense against OS, plays an essential role in neuroprotection by regulating the expressions of antioxidant molecules and enzymes. However, simultaneous events resulting in the overproduction of reactive oxygen species (ROS) and deregulation of the Nrf2-ARE system damage essential cell components and cause loss of neuron structural and functional integrity. On the other hand, TrkB (tropomyosin-related kinase B) signaling, a classical neurotrophin signaling pathway, regulates neuronal survival and synaptic plasticity, which play pivotal roles in memory and cognition. Also, TrkB signaling, specifically the TrkB/PI3K/Akt (TrkB/phosphatidylinositol 3 kinase/protein kinase B) pathway promotes the activation and nuclear translocation of Nrf2, and thus, confers neuroprotection against OS. However, the TrkB signaling pathway is also known to be downregulated in brain disorders due to lack of neurotrophin support. Therefore, activations of TrkB and the Nrf2-ARE signaling system offer a potential approach to the design of novel therapeutic agents for brain disorders. Here, we briefly overview the development of OS and the association between OS and the pathogenesis of neurodegenerative diseases and brain injury. We propose the cellular antioxidant defense and TrkB signaling-mediated cell survival systems be considered pharmacological targets for the treatment of neurodegenerative diseases, and review the literature on the neuroprotective effects of phytochemicals that can co-activate these neuronal defense systems.

Phytosterols of marine algae: Insights into the potential health benefits and molecular pharmacology.

BACKGROUND: Marine algae are rich in some unique biologically active secondary metabolites having diverse pharmacological benefits. Of these, sterols comprise a group of functional lipid compounds that have attracted much attention to natural product scientists. PURPOSE: This review was aimed to update information on the health effects of algae-derived phytosterols and their molecular interactions in various aspects of human health and diseases and to address some future perspectives that may open up a new dimension of pharmacological potentials of algal sterols. METHODS: A literature-based search was carried out to retrieve published research information on the potential health effects of algal phytosterols with their pharmacological mechanisms from accessible online databases, such as Pubmed, Google Scholar, Web of Science, and Scopus, using the key search terms of 'marine algae sterol' and 'health potentials such as antioxidant or anti-inflammatory or anti-Alzheimer's or anti-obesity or cholesterol homeostasis or hepatoprotective, antiproliferative, etc.' RESULTS: Phytosterols of marine algae, particularly fucosterol, have been investigated for a plethora of health benefits, including anti-diabetes, anti-obesity, anti-Alzheimer's, antiaging, anticancer, and hepatoprotection, among many others, which are attributed to their antioxidant, anti-inflammatory, immunomodulatory and cholesterol-lowering properties, indicating their potentiality as therapeutic leads. These sterols interact with enzymes and various other proteins that are actively participating in different cellular pathways, including antioxidant defense system, apoptosis and cell survival, metabolism, and homeostasis. CONCLUSION: In this review, we briefly overview the chemistry, pharmacokinetics, and distribution of algal sterols, and provide critical insights into their potential health effects and the underlying pharmacological mechanisms, beyond the well-known cholesterol-lowering paradigm.

Gelidium amansii Attenuates Hypoxia/Reoxygenation-Induced Oxidative Injury in Primary Hippocampal Neurons through Suppressing GluN2B Expression.

Oxidative stress is known to be critically implicated in the pathophysiology of several neurological disorders, including Alzheimer's disease and ischemic stroke. The remarkable neurotrophic activity of Gelidium amansii, which has been reported consistently in a series of our previous studies, inspired us to investigate whether this popular agarophyte could protect against hypoxia/reoxygenation (H/R)-induced oxidative injury in hippocampal neurons. The primary culture of hippocampal neurons challenged with H/R suffered from a significant loss of cell survival, accompanied by apoptosis and necrosis, DNA damage, generation of reactive oxygen species (ROS), and dissipation of mitochondrial membrane potential (ΔΨm), which were successfully attenuated when the neuronal cultures were preconditioned with ethanolic extract of G. amansii (GAE). GAE also attenuated an H/R-mediated increase of BAX and caspase 3 expressions while promoting Bcl-2 expression. Moreover, the expression of N-methyl-d-acetate receptor subunit 2B (GluN2B), an extrasynaptic glutamate receptor, was significantly repressed, while synaptic GluN2A expression was preserved in GAE-treated neurons as compared to those without GAE intervention. Together, this study demonstrates that GAE attenuated H/R-induced oxidative injury in hippocampal neurons through, at least in part, a potential neuroprotective mechanism that involves inhibition of GluN2B-mediated excitotoxicity and suppression of ROS production, and suggests that this edible seaweed could be a potential source of bioactive metabolites with therapeutic significance against oxidative stress-related neurodegeneration, including ischemic stroke and neurodegenerative diseases.