Anthracene detoxification by Laccases from indigenous fungal strains Trichoderma lixii FLU1 and Talaromyces pinophilus FLU12.

The persistence and ubiquity of polycyclic aromatic hydrocarbons (PAHs) in the environment necessitate effective remediation strategies. Hence, this study investigated the potential of purified Laccases, TlFLU1L and TpFLU12L, from two indigenous fungi Trichoderma lixii FLU1 (TlFLU1) and Talaromyces pinophilus FLU12 (TpFLU12), respectively for the oxidation and detoxification of anthracene. Anthracene was degraded with vmax values of 3.51 ± 0.06 mg/L/h and 3.44 ± 0.06 mg/L/h, and Km values of 173.2 ± 0.06 mg/L and 73.3 ± 0.07 mg/L by TlFLU1L and TpFLU12L, respectively. The addition of a mediator compound 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) to the reaction system significantly increased the degradation of anthracene, with up to a 2.9-fold increase in vmax value and up to threefold decrease in Km values of TlFLU1L and TpFLU12L. The GC-MS analysis of the metabolites suggests that anthracene degradation follows one new pathway unique to the ABTS system-hydroxylation and carboxylation of C-1 and C-2 position of anthracene to form 3-hydroxy-2-naphthoic acid, before undergoing dioxygenation and side chain removal to form chromone which was later converted into benzoic acid and CO2. This pathway contrasts with the common dioxygenation route observed in the free Laccase system, which is observed in the second degradation pathways. Furthermore, toxicity tests using V. parahaemolyticus and HT-22 cells, respectively, demonstrated the non-toxic nature of Laccase-ABTS-mediated metabolites. Intriguingly, analysis of the expression level of Alzheimer's related genes in HT-22 cells exposed to degradation products revealed no induction of neurotoxicity unlike untreated cells. These findings propose a paradigm shift for bioremediation by highlighting the Laccase-ABTS system as a promising green technology due to its efficiency with the discovery of a potentially less harmful degradation pathway, and the production of non-toxic metabolites.

Assessment of Neurotoxic Mechanisms of Individual and Binary Mixtures of Cobalt, Nickel and Lead in Hippocampal Neuronal Cells.

Many studies have focused on the neurotoxic effects of single metals, while investigation on the exposure to metal mixtures, which mainly occur in real-life situations, is scarce. This study sought to assess the neurotoxic effect of Ni, Co, and Pb binary mixtures and their individual effects in hippocampal neuronal cells (HT-22). Cells were exposed to Ni, Co, and Pb separately for 48 h at 37°C and 5% CO2, and cell viability was assessed. Morphological assessment of the cells exposed to binary mixtures of Co, Ni, and Pb and single metals was assessed using a microscope. Furthermore, acetylcholinesterase (AChE) activity, oxidative stress biomarkers (glutathione [GSH] and malondialdehyde [MDA] levels, catalase [CAT], and glutathione-S transferase [GST] activities) and nitric oxide [NO] levels were evaluated after treatment with the binary mixtures and single metals. Binary mixtures of the metals reduced cell viability, exerting an additivity action. The combinations also exerted synergistic action, as revealed by the combination index. Furthermore, a significant reduction in AChE activity, GSH levels, CAT and GST activities, and high MDA and NO levels were observed in neuronal cells. The additive interactions and synergistic actions of the binary mixtures might contribute to the significant reduction of AChE activity, GSH levels, GST, and CAT activities, and an increase in MDA and NO levels. The findings from this study revealed significant evidence that binary mixtures of Co, Pb, and Ni may induce impaired neuronal function and, ultimately, neurodegeneration.

Apigenin and inflammation in the brain: can apigenin inhibit neuroinflammation in preclinical models?

Apigenin is a flavone-kind of flavonoid present in fruits and vegetables. Apigenin exhibits biological activities including neuropharmacological effects against different neurological disorders. In this study, we summarize and discuss the molecular mechanisms of the anti-neuroinflammatory effects of apigenin in neurological disorders. A systematic review was conducted by searching Google Scholar, Web of Science, Scopus and PubMed. A total of 461 records were retrieved from the search. After screening of the records based on the inclusion criteria, 16 articles were selected and discussed in this study. The results from the selected studies showed that apigenin exhibited anti-neuroinflammatory effect in preclinical studies. The anti-neuroinflammatory mechanisms exhibited by apigenin include inhibition of overproduction of pro-inflammatory cytokines, attenuation of microglia activation via reduction of CD-11b-positive cells, inhibition of ROCK-1 expression and upregulation of miR-15a, p-ERK1/2, p-CREB, and BDNF, downregulation of NLRP3 inflammasome, iNOS and COX-2 expression, reduction of Toll-like receptor-4 expression and inhibition of nuclear factor-kappa B (NF-kB) activation. Overall, apigenin inhibited neuroinflammation which suggests it confers neuroprotective effect against neuronal degeneration in some neurodegenerative conditions. This review provides important neuropharmacological information on the neuroprotective mechanisms of apigenin against neuroinflammation which may be useful for future preclinical and clinical studies.

Effect of diet supplemented with African Star Apple Fruit Pulp on purinergic, cholinergic and monoaminergic enzymes, TNF-α expression and redox imbalance in the brain of hypertensive rats.

OBJECTIVE: This study examined whether diet supplemented with African star apple fruit pulp (FP) can mitigate the effect of high blood pressure on brain neurochemicals, histopathology and expression of genes linked with neuroinflammation. METHODS: Rats were administered with cyclosporine (25 mg/kg.bw) to induce hypertension and were fed with or without FP supplemented diet. Purinergic (Nucleoside triphosphate diphosphohydrolases [NTPdase] and adenosine deaminase [ADA]) cholinergic (acetylcholinesterase [AChE]) and monoaminergic (monoamine oxidase-B) enzymes were assessed in treated and untreated hypertensive rats' brains. Oxidative stress biomarkers (catalase, glutathione-S-transferase, thiols, reactive oxygen species [ROS] and malondialdehyde [MDA]), as well as AChE, tumour necrosis factor and receptor (TNF-α and TNF-α-R) expression, were also determined. RESULTS: FP supplemented diet significantly reduced NTPdase and ADA activities and increased Na+/K+-ATPase activities in hypertensive rats' brains compared to the untreated group. Furthermore, FP reduced acetylcholinesterase and monoamine oxidase-B activities compared to the hypertensive group. Redox imbalance was observed in hypertensive rats with inhibition of antioxidant enzymes and high levels of ROS and MDA. However, FP supplemented diet improved antioxidant enzymes, reduced ROS and MDA production in the brain of hypertensive rats. High blood pressure also triggered upregulation of AChE, TNF-α and TNF-α-R while feeding with FP supplemented diet downregulated the genes. CONCLUSION: This study demonstrates the neuroprotective role of FP supplemented diet against alterations in neurochemicals associated with Alzheimer's disease, oxidative stress-induced neuronal damage and expression of genes linked with neuroinflammation. Moreover, studies on animal behaviour and human subjects are required to confirm these beneficial effects.

Hibiscus sabdariffa (Roselle) calyx: a systematic and meta-analytic review of memory-enhancing, anti-neuroinflammatory and antioxidative activities.

BACKGROUND: In this study, we summarized the preclinical investigations of the neuroprotective activities of Hibiscus sabdariffa (HSD) extract via its effect on memory function, neuroinflammation and oxidative damage in the central nervous system, which may help to guide future studies. METHODS: Preclinical studies that investigated the effect of HSD extract on memory impairment, neuroinflammation and oxidative stress-induced neuronal damage were searched systematically in PubMed, EBSCOhost (including MEDLINE, CINAHL, APA PsycInfo, etc.), Web of Science (WoS) and Scopus. Parameters and indexes included Morris water maze, passive avoidance test, acetylcholinesterase activity, interleukin 1 (IL-1), tumour necrosis factor-alpha (TNF-α), MAPK, malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS) and mitochondria membrane potential (MMP). RESULTS: A total of 285 documents were identified; however, only ten articles were included and used for meta-analysis. The meta-analytic outcome revealed that HSD did not show any significant effect on memory function, neuroinflammatory biomarkers (IL-1, MAPK) and oxidative stress (GSH, MDA, ROS and MMP) in neuronal cells and tissues. CONCLUSIONS: Individual study revealed that HSD showed improved memory function, attenuated neuroinflammation and prevented oxidative damage to neurons. However, a conflicting result was observed from the meta-analytic outcomes which showed that HSD has no significant effect on cognitive impairment, neuroinflammation and oxidative stress-induced neuronal damage. However the contradiction in this finding may be associated with small number of studies included. Hence, more studies on the memory-enhacing effects and anti-neuroinflammatory activity of HSD in preclinical and clinical model are required to validate its neuroprotective effect.

Neuroprotective properties of solanum leaves in transgenic Drosophila melanogaster model of Alzheimer's disease.

INTRODUCTION: We investigated the effect of African eggplant (AE) (Solanum macrocarpon L) and Black nightshade (BN) (Solanum nigrum L) leaves; two tropical vegetables consumed by humans on behavioural, biochemical and histological indices in Drosophila melanogaster model of Alzheimer's disease (AD). MATERIALS AND METHOD: Transgenic flies expressing human Amyloid Precursor Protein (hAPP) and ß-secretase (hBACE 1) were exposed to the pulverised leaf samples (0.1 and 1.0%) in their diets for fourteen days. Thereafter, the flies were assessed for their behavioural indices and routine histology of brain cells. Furthermore, fly head homogenates were assayed for ß-amyloid level, activities of acetylcholinesterase (AChE) and ß-secretase (BACE-1), as well as oxidative stress markers. RESULTS: Result showed that the significantly lower (p < 0.05) behavioural parameters (survival, locomotor performance and memory index), higher AChE and BACE-1 activities, ß-amyloid, ROS and lipid peroxidation levels, as well as reduced antioxidant indices observed in the AD flies, were significantly ameliorated (p < 0.05) in AD flies treated with the leaf samples. DISCUSSION: This study has showed that leaves of AE and BN ameliorated behavioural and biochemical indices in AD flies via neural enzyme modulatory, and antioxidant mechanisms. CONCLUSION: Hence, this study further justifies the neuroprotective properties of both AE and BN.

Beetroot supplemented diet exhibit anti-amnesic effect via modulation of cholinesterases, purinergic enzymes, monoamine oxidase and attenuation of redox imbalance in the brain of scopolamine treated male rats.

OBJECTIVES: Beta vulgaris, commonly known as beetroot, is a vegetable that contains red pigment and rich in betalains, phenolic acids, and flavonoids. This study was designed to assess the effect of beetroot supplemented diet (BRSD) on cognitive function and altered neurochemicals associated with Alzheimer's disease (AD) in the brain of rats treated with scopolamine (SCOP). METHODS: Rats were fed with BRSD (2 and 4%) for 14 days and administered with 2 mg/kg of SCOP intraperitoneally on the last day. Morris water Maze and Y-maze tests were performed to assess cognitive function. Purinergic enzymes [ectonucleotidase (NTPdase) and adenosine deaminase (ADA)], monoamine oxidase (MAO), and angiotensin-I converting enzyme (ACE) activities were determined in rat brain tissues. Furthermore, catalase activity, total thiol (T-SH) and non-protein thiol (NP-SH) levels were also assessed. Beetroot was characterized using liquid chromatography-mass spectrometry, and the structure-activity relationship between the constituents and target enzymes was assessed. RESULTS: BRSD improved cognitive function by increasing memory index in SCOP treated rats. An increase in NTPdase, ADA, MAO, and ACE activities were observed in the brain of rats treated with SCOP. However, the activities of these enzymes were significantly lower after treatment with BRSD. Treatment with BRSD triggered a significant increase in catalase activity, T-SH and NP-SH levels in SCOP-treated rats. Catechin, 6,7-benzocoumarin, gentisin, 5,7-dimethoxyflavone, and vulgaxanthin I was identified in beetroots. DISCUSSION: The result suggests that beetroot could prevent cognitive dysfunction in SCOP-treated rats, and enhance memory function, via modulation of purinergic enzymes, MAO and ACE activities, and neuronal antioxidant status.

Modulatory effects of stonebreaker (Phyllanthus amarus) and bitter gourd (Momordica charantia) on enzymes linked with cardiac function in heart tissue of doxorubicin-stressed rats.

Doxorubicin (DOX) has been linked with impairment in cardiovascular function and redox balance. In the present study, the effect of Phyllanthus amarus (PA) and Momordica charantia (MC) leaves on some biomolecules [Angiotensin-I converting enzyme (ACE), arginase, acetylcholinesterase (AChE), adenosine deaminase (ADA), lactate dehydrogenase (LDH)] and antioxidant [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA)] linked with cardiac function in DOX-stressed rats was evaluated. Animals were grouped and pretreated with PA and MC leaf extracts at different doses (200 and 400 mg/kg/bwt orally), while DOX (15 mg/kg/bwt) was administered intraperitoneally on the last day of the experiment. Result revealed an increase of ACE, arginase, AChE, ADA, LDH activities and MDA level as well as a significant reduction in CAT and SOD activities, and GSH level in the rats treated with DOX compared to the control. However, these were significantly mitigated in the rats pretreated with PA and MC dose dependently. Chemical characterization of the leaf extracts via high performance liquid chromatography revealed the presence of some phenolic compounds which included kaempferol, catechin, epicatechin, ellagic acid, gallic acid quercetin, isoquercitrin and rutin. These findings revealed a significant improvement in redox imbalance and other biomolecules associated with cardiac function, which was altered by DOX. This improvement could be linked to the presence of cardioprotective agents present in PA and MC, thereby making these plants therapeutic agents for the treatment of cardiovascular complications associated with drugs such as DOX.

Chemical Characterization, Antiproliferative and Antioxidant Activities of Polyunsaturated Fatty Acid-Rich Extracts from Chlorella sp. S14.

Microalgae is a rich source of polyunsaturated fatty acid. This study was conducted to identify and isolate microalgal strain with the potentials for producing polyunsaturated fatty acids (PUFAs) and determine its cytotoxic effect on some cancer cells. The algal strain (Chlorella sp. S14) was cultivated using modified BG-11 media, and algal biomass obtained was used for fatty acid extraction. Gas chromatographic-mass spectrometry was used to identify and quantify the levels of the fatty acid constituents. The total content of monounsaturated fatty acids (1.12%) was low compared to polyunsaturated fatty acids (PUFAs) (52.87%). Furthermore, n-3 PUFAs accounted for (12.37%) of total PUFAs with the presence of α-linolenic acid (2.16%) and cis-11,14,17-eicosatrienoic acid (2.16%). The PUFA-rich extract did not exhibit a cytotoxic effect on normal cells. Treatment with the PUFA-rich extract (150 µg/mL) significantly reduced cell viability in MCF-7 (31.58%) and A549 (62.56%) cells after the 48 h treatment. Furthermore, treatment of MCF-7 with fatty acid extracts (125 and 150 µg/mL) showed a significant reduction in MDA levels, increase in catalase activities and decrease in GSH level compared to untreated cells. However, a slight decrease in MDA level was observed in A549 cells after the 48 h treatment. There are no significant changes in catalase activities and GSH level in treated A549 cells. However, a slight reduction of NO levels was observed in treated MCF-7 and A549 cells. These results indicate the potentials of PUFA-rich extracts from Chlorella sp. S14 to reduce viability and modulate redox status in A549 and MCF-7 cells.

Vanillin and vanillic acid modulate antioxidant defense system via amelioration of metabolic complications linked to Fe2+-induced brain tissues damage.

The therapeutic effect of phenolics on neurodegenerative diseases has been attributed to their potent antioxidant properties. In the present study, the neuroprotective activities of vanillin and vanillic acid were investigated in Fe2+- induced oxidative toxicity in brain tissues by investigating their therapeutic effects on oxidative imbalance, cholinergic and nucleotide-hydrolyzing enzymes activities, dysregulated metabolic pathways. Their cytotoxicity was investigated in hippocampal neuronal cell lines (HT22). The reduced glutathione level, SOD and catalase activities were ameliorated in tissues treated with the phenolics, with concomitant depletion of malondialdehyde and nitric oxide levels. They inhibited acetylcholinesterase and butyrylcholinesterase activities, while concomitantly elevated ATPase activity. Treatment with vanillin led to restoration of oxidative-depleted metabolites and reactivation of the pentose phosphate and purine metabolism pathways, with concomitant activation of pathways for histidine and selenoamino metabolisms. While vanillic acid restored and reactivated oxidative-depleted metabolites and pathways but did not activate any additional pathway. Both phenolics portrayed good binding affinity for catalase, with vanillic acid having the higher binding energy of -7.0 kcal/mol. Both phenolics were not cytotoxic on HT22 cells, and their toxicity class were predicted to be 4. Only vanillin was predicted to be permeable across the blood brain barrier (BBB). These results insinuate that vanillin and vanillic acid confer a neuroprotective effect on oxidative brain damage, when vanillin being the most potent.

Neuroprotective effects of some seaweeds against Zn - induced neuronal damage in HT-22 cells via modulation of redox imbalance, inhibition of apoptosis and acetylcholinesterase activity.

Zinc plays an important role in neuronal signaling and neurotransmission. However, dyshomeostasis of this metal or its accumulation in the brain has been linked with neurological disorders such as Alzheimer's disease and Parkinson's disease. In this study, the neuroprotective effects of Ecklonia maxima (KPM), Gracilaria gracilis (GCL), Ulva lactuca (ULT) and Gelidium pristoides (MNP) in Zn -induced neurotoxicity in HT-22 cells was examined. Cells were treated with Zinc sulphate and/or aqueous - ethanol extracts and cell viability, apoptosis, acetylcholinesterase activity, including some antioxidant enzymes (catalase and superoxide dismutase activity) and glutathione (GSH) levels were determined. Malondialdehyde and nitric oxide levels produced in the Zn and/or seaweed extract treated cells were also determined. Prior treatment with the seaweed extracts improved cell viability and inhibited Zn - induced cell death. Acetylcholinesterase activity was significantly high in Zn treated cells compared to the control. Pre-treatment with the seaweed extracts triggered a decrease in acetylcholinesterase activity in Zn - treated cells. Furthermore, treatment with Zn caused a significant reduction in GSH levels as well as a decrease in superoxide dismutase and catalase activities. In contrast, the seaweed extract increased antioxidant enzyme activities and GSH levels. An increase in malondialdehyde and nitric oxide levels was also reversed after treatment with the seaweed extracts. These results suggest that the seaweed extracts improved cholinergic transmission disrupted by Zn - induced neurotoxicity and protected the cells against oxidative damage and neuroinflammation. The neuroprotective effects of the seaweed extracts could be linked to their bioactive constituents. Hence these seaweeds are potential sources of active ingredients with neuroprotective potentials and could be used for the development of functional foods and/or nutraceuticals.

Macroalgae as a Valuable Source of Naturally Occurring Bioactive Compounds for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurological condition that affects mostly aged individuals. Evidence suggests that pathological mechanisms involved in the development of AD are associated with cholinergic deficit, glutamate excitotoxicity, beta-amyloid aggregation, tau phosphorylation, neuro-inflammation, and oxidative damage to neurons. Currently there is no cure for AD; however, synthetic therapies have been developed to effectively manage some of the symptoms at the early stage of the disease. Natural products from plants and marine organisms have been identified as important sources of bioactive compounds with neuroprotective potentials and less adverse effects compared to synthetic agents. Seaweeds contain several kinds of secondary metabolites such as phlorotannins, carotenoids, sterols, fucoidans, and poly unsaturated fatty acids. However, their neuroprotective effects and mechanisms of action have not been fully explored. This review discusses recent investigations and/or updates on interactions of bioactive compounds from seaweeds with biomarkers involved in the pathogenesis of AD using reports in electronic databases such as Web of science, Scopus, PubMed, Science direct, Scifinder, Taylor and Francis, Wiley, Springer, and Google scholar between 2015 and 2019. Phlorotannins, fucoidans, sterols, and carotenoids showed strong neuroprotective potentials in different experimental models. However, there are no data from human studies and/or clinical trials.

Phenolic composition, antioxidant activity, anticholinesterase potential and modulatory effects of aqueous extracts of some seaweeds on ß-amyloid aggregation and disaggregation.

Context: Seaweeds contain bioactive compounds with different biological activities. They are used as functional ingredients for the development of therapeutic agents to combat degenerative diseases. Objective: This study investigated the phenolic composition, antioxidant activity, cholinesterase inhibitory and anti-amyloidogenic activities of aqueous extracts of Gracilaria beckeri (J.Agardh) Papenfuss (Gracilariaceae) (RED-AQ), Ecklonia maxima (Osbeck) Papenfuss (Lessoniaceae) (ECK-AQ), Ulva rigida (C.Agardh) Linnaeus (Ulvaceae) (URL-AQ) and Gelidium pristoides (Turner) Kützing (Gelidiaceae) (GEL-AQ). Materials and methods: Phenolic composition of the seaweed extracts was determined using liquid chromatography mass spectrometry. Radical scavenging and metal chelating activities were assessed in vitro. The effect of the extracts (21-84 µg/mL) on acetylcholinesterase and butyrylcholinesterase activities were also investigated using an in vitro colorimetric assay. Transmission electron microscope and thioflavin-T fluorescence assay were used to examine the anti-amyloidogenic activities of the extracts. Results: Phloroglucinol, catechin, epicatechin 3-glucoside were identified in the extracts. ECK-AQ (IC50=30.42 and 280.47 µg/mL) exhibited the highest OH• scavenging and metal chelating activities, while RED-AQ (41.23 and 334.45 µg/mL) exhibited the lowest. Similarly, ECK-AQ (IC50 = 49.41 and 52.11 µg/mL) exhibited higher inhibitory effects on acetylcholinesterase and butyrylcholinesterase activities, while RED-AQ (64.56 and 63.03 µg/mL) showed the least activities. Rapid formation of ß-amyloid (Aß1-42) fibrils and aggregates was observed in electron micrographs of the control after 72 and 96 h. The reduction of Aß1-42 aggregates occurred after co-treatment with the seaweed extracts. Discussion and conclusion: ECK-AQ, GEL-AQ, URL-AQ and RED-AQ may possess neuroprotective potential and could be explored for the management of Alzheimer's disease.

Moringa oleifera supplemented diet modulates nootropic-related biomolecules in the brain of STZ-induced diabetic rats treated with acarbose.

There are strong correlations between diabetes mellitus and cognitive dysfunction. This study sought to investigate the modulatory effects of Moringa oleifera leaf (ML) and seed (MS) inclusive diets on biomolecules [acetylcholinesterase (AChE), butyrylcholinesterase (BChE)] angiotensin-I converting enzyme (ACE), arginase, catalase, glutathione transferase (GST) and glutathione peroxidase (GSH-Px) activities, glutathione (GSH) and nitric oxide (NO) levels] associated with cognitive function in the brain of streptozotocin (STZ)-induced diabetic rats treated with acarbose (ACA). The rats were made diabetic by intraperitoneal administration of 0.1 M sodium-citrate buffer (pH 4.5) containing STZ [60 mg/kg b.w (BW)] and fed with diets containing 2 and 4% ML/MS. Acarbose (25 mg/kg BW) was administered by gavage daily for 14 days. The animals were distributed in eleven groups of eight animals as follows: control, STZ-induced, STZ + ACA, STZ + 2% ML, STZ + ACA + 2% ML, STZ + 4% ML, STZ + ACA + 4% ML, STZ + 2% MS, STZ + ACA + 2% MS, STZ + 4% MS, STZ + ACA + 4% MS. There were marked increase in AChE, BChE, arginase, ACE and concomitant decrease in catalase, GST, GSH-Px, activities and NO levels in STZ-diabetic group compared with the control. However, there was a decrease in AChE, BChE and ACE activities and concomitant increase in the antioxidant molecules in the groups fed with supplemented diets treated with/without ACA compared with the STZ-diabetic group. These findings suggest that ML/MS supplemented diet could prevent cognitive dysfunction-induced by chronic hyperglycemia.

Therapeutic Potentials of Microalgae in the Treatment of Alzheimer's Disease.

Current research is geared towards the discovery of new compounds with strong neuroprotective potential and few or no side effects compared to synthetic drugs. This review focuses on the potentials of extracts and biologically active compounds derived from microalgal biomass for the treatment and management of Alzheimer's disease (AD). Microalgal research has gained much attention recently due to its contribution to the production of renewable fuels and the ability of alga cells to produce several secondary metabolites such as carotenoids, polyphenols, sterols, polyunsaturated fatty acids and polysaccharides. These compounds exhibit several pharmacological activities and possess neuroprotective potential. The pathogenesis of Alzheimer's disease (AD) involves complex mechanisms that are associated with oxidative stress, cholinergic dysfunction, neuronal damage, protein misfolding and aggregation. The antioxidant, anticholinesterase activities as well as the inhibitory effects of some bioactive compounds from microalgae extracts on ß-amyloid aggregation and neuronal death are discussed extensively. Phytochemical compounds from microalgae are used as pharmaceuticals, nutraceuticals and food supplements, and may possess neuroprotective potentials that are relevant to the management and/or treatment of AD.

The Beneficial Role of Apigenin against Cognitive and Neurobehavioural Dysfunction: A Systematic Review of Preclinical Investigations.

Apigenin is a flavone widely present in different fruits and vegetables and has been suggested to possess neuroprotective effects against some neurological disorders. In this study, we systematically reviewed preclinical studies that investigated the effects of apigenin on learning and memory, locomotion activity, anxiety-like behaviour, depressive-like behaviour and sensorimotor and motor coordination in rats and mice with impaired memory and behaviour. We searched SCOPUS, Web of Science, PubMed and Google Scholar for relevant articles. A total of 34 studies were included in this review. The included studies revealed that apigenin enhanced learning and memory and locomotion activity, exhibited anxiolytic effects, attenuated depressive-like behaviour and improved sensorimotor and motor coordination in animals with cognitive impairment and neurobehavioural deficit. Some of the molecular and biochemical mechanisms of apigenin include activation of the ERK/CREB/BDNF signalling pathway; modulation of neurotransmitter levels and monoaminergic, cholinergic, dopaminergic and serotonergic systems; inhibition of pro-inflammatory cytokine production; and attenuation of oxidative neuronal damage. These results revealed the necessity for further research using established doses and short or long durations to ascertain effective and safe doses of apigenin. These results also point to the need for a clinical experiment to ascertain the therapeutic effect of apigenin.

Antidiabetic potentials of crude and purified sulphated polysaccharides isolated from Gracilaria gracilis, a seaweed from South Africa.

Over 90 % of all cases of diabetes that have been diagnosed are type 2 diabetes (T2D), a disease exacerbated by an increase in sedentary behaviour, bad eating habits, and obesity. This study investigated the antidiabetic properties of Gracilaria gracilis, using in vitro and ex vivo experimental models. The sulphated polysaccharides (SPs) from crude extracts of the seaweed powder was prepared via hot (100°C) and cold (25°C) aqueous extraction procedures before purification via an anion exchange chromatographic technique. Both the crude and purified extracts were characterised by Fourier-transform infrared spectroscopy (FT-IR), LC-MS analysis, and Nuclear Magnetic Resonance (NMR) spectroscopy. The crude cold-aqueous and purified hot-aqueous SPs from G. gracilis had the strongest α-glucosidase inhibitory effect with IC50 value of 0.15 and 0.07 mg/ml, respectively. The purified cold-aqueous SP was the most potent inhibitor of α-glucosidase with an IC50 value of 0.17 mg/ml. The crude and purified SP-rich extracts inhibited pancreatic lipase (hot aqueous SP = 0.03 mg/ml) activity and effectively stimulated glucose uptake in yeast cells. Moreover, they showed significantly (p < 0.05) better intestinal glucose absorption inhibitory properties at the highest concentration (1 mg/ml) and displayed significantly (p < 0.05) better muscle glucose uptake compared to the commercial antidiabetic drug, metformin, at the same concentration. Overall, the current findings indicate that G. gracilis SPs may inhibit carbohydrate-hydrolysing enzymes, limit the release of simple sugars from the gut whilst effectively stimulating the use of glucose by peripheral tissue thus may be suitable to develop antidiabetic food supplements after further animal and clinical trials.

Antiproliferative and apoptosis-inducing effects of aqueous extracts from Ecklonia maxima and Ulva rigida on HepG2 cells.

This study examined the antiproliferative and apoptotic-inducing effects of Ecklonia maxima (KP) and Ulva rigida (URL) extracts in the human liver cancer (HepG2) cell line model. HepG2 cells were cultured and grown in an incubator (5% CO2 ) at 37°C. Cell viability was determined, while the effect of the extracts on apoptosis, ROS production, mitochondria membrane potential, and antioxidant enzymes were also assessed. KP and URL induced cytotoxic effects on HepG2 cells at the concentrations tested (0-1000 µg/ml). The morphological characteristics of the cells after treatment with KP and URL revealed cell shrinkage of the nucleus, cell injury, and damage compared to the control. The fluorescent micrographs from the apoptotic assay revealed induction of apoptosis and necrosis in HepG2 cells after treatment with KP and URL (200 and 400 µg/ml). The extracts also induced ROS production and reduced mitochondria membrane potential in HepG2 cells. The apoptotic-inducing effects, activation of ROS generation, and disruption of antioxidant enzymes are associated with the cytotoxic effects of the seaweed extracts. KP and URL showed good anticancer properties and could be explored as a good source of nutraceuticals, food additives, and dietary supplements to prevent uncontrolled proliferation of HepG2 cells. PRACTICAL APPLICATIONS: Seaweeds are reservoirs of nutrients and naturally occurring biologically active compounds, including sterols, phlorotannins, and polyunsaturated fatty acids. Due to the presence of these compounds, they are used as emulsifying agents, nutraceuticals, and additives in functional foods. Evidence suggests that seaweed bioactives may inhibit uncontrolled cell proliferation and induce apoptosis in cancer cells. Hence, exploring the antiproliferative and apoptotic-inducing effects of Ecklonia maxima and Ulva rigida will provide insights into their anticancer potentials as functional foods and nutraceuticals.

Neurotoxicity of anthracene and benz[a]anthracene involves oxidative stress-induced neuronal damage, cholinergic dysfunction and disruption of monoaminergic and purinergic enzymes.

In this study, the modulatory effects of anthracene (ANT) and benz[a]anthracene (BEN) on biochemical markers associated with neurodegeneration were assessed in mouse hippocampal neuronal cells (HT-22). Neuronal cells were cultured and exposed to ANT and BEN (25-125 µM) for 5 days, and the cell viability was determined via MTT assay. Morphological characteristics of the cells were assessed using a compound microscope. Biochemical parameters such as acetylcholinesterase (AChE), monoamine oxidase (MAO) and adenosine deaminase (ADA) activities as well as oxidative stress biomarkers (catalase [CAT], glutathione -S- transferase [GST] activities and Glutathione [GSH] levels) and nitric oxide [NO] levels were assessed after cells were treated with ANT and BEN for two days. The results showed that cell viability reduced with an increase in exposure time. After the fifth day of treatment, BEN and ANT (125 µM) reduced percentage viability to 41 and 38.1%, respectively. Light micrographs showed shrinkage of cells, neuronal injury and cell death in cells treated with higher concentrations of BEN and ANT (50 and 125 µM). Furthermore, AChE and MAO activities reduced significantly after treatment for 48 h with ANT and BEN. A significant decrease in CAT and GST activities and low GSH levels were observed after treatment with BEN and ANT. However, both polycyclic aromatic hydrocarbons caused a significant increase in ADA activity and NO levels. These results suggest that ANT and BEN may induce neurodegeneration in neuronal cells via oxidative stress-induced-neuronal injury, disruption of cholinergic, monoaminergic and purinergic transmission, and increased nitric oxide levels.

Neurotoxicity of Polycyclic Aromatic Hydrocarbons: A Systematic Mapping and Review of Neuropathological Mechanisms.

Several studies present the neurotoxic effects of polycyclic aromatic hydrocarbons (PAHs), a class of environmental pollutants capable of causing neurological deficits. However, a collective review approach to this research topic is scarce. This study presents the effect of PAHs on the central nervous system using a bibliometric approach. The neuropathological mechanisms of PAHs are also highlighted. Published articles were searched for in the Scopus and Web of Science databases from January 1979 to December 2020 using the keywords 'polycyclic aromatic hydrocarbons' and 'neurotoxicity'. The total number of documents retrieved from both databases was 338. Duplicated documents (80) were excluded and 258 articles were used for the final analysis. Our findings revealed that there has been a significant increase in research outputs on this topic in the last ten years. The countries with the highest scientific productivity in this area are USA, China, France and Italy. The result also showed that, in the past few years, global scientific output in research relating to PAH neurotoxicity focused on neurodegeneration, cholinergic function, neurodevelopmental toxicity, behavioural studies, oxidative stress, neuroprotection and therapeutic intervention using different experimental models, including zebrafish, neuronal cell lines, Caenorhabditis elegans and rats. Recent studies also revealed the neuroprotective roles of some natural products against PAH-induced neurotoxicity. However, more investigation involving clinical trials is required to emphasize the observed neurotoxic effects.