Characterisation of the Paenarthrobacter nicotinovorans ATCC 49919 genome and identification of several strains harbouring a highly syntenic nic-genes cluster.

BACKGROUND: Paenarthrobacter nicotinovorans ATCC 49919 uses the pyridine-pathway to degrade nicotine and could provide a renewable source of precursors from nicotine-containing waste as well as a model for studying the molecular evolution of catabolic pathways and their spread by horizontal gene transfer via soil bacterial plasmids. RESULTS: In the present study, the strain was sequenced using the Illumina NovaSeq 6000 and Oxford Nanopore Technology (ONT) MinION platforms. Following hybrid assembly with Unicycler, the complete genome sequence of the strain was obtained and used as reference for whole-genome-based phylogeny analyses. A total of 64 related genomes were analysed; five Arthrobacter strains showed both digital DNA-DNA hybridization and average nucleotide identity values over the species threshold when compared to P. nicotinovorans ATCC 49919. Five plasmids and two contigs belonging to Arthrobacter and Paenarthrobacter strains were shown to be virtually identical with the pAO1 plasmid of Paenarthrobacter nicotinovorans ATCC 49919. Moreover, a highly syntenic nic-genes cluster was identified on five plasmids, one contig and three chromosomes. The nic-genes cluster contains two major locally collinear blocks that appear to form a putative catabolic transposon. Although the origins of the nic-genes cluster and the putative transposon still elude us, we hypothesise here that the ATCC 49919 strain most probably evolved from Paenarthrobacter sp. YJN-D or a very closely related strain by acquiring the pAO1 megaplasmid and the nicotine degradation pathway. CONCLUSIONS: The data presented here offers another snapshot into the evolution of plasmids harboured by Arthrobacter and Paenarthrobacter species and their role in the spread of metabolic traits by horizontal gene transfer among related soil bacteria.

Advances in Characterizing the Transport Systems of and Resistance to EntDD14, A Leaderless Two-Peptide Bacteriocin with Potent Inhibitory Activity.

Enterocin DD14 (EntDD14) is a two-peptide leaderless bacteriocin produced by the Enterococcus faecalis 14 strain previously isolated from meconium. This bacteriocin is mainly active against Gram-positive bacteria. Leaderless bacteriocins do not undergo post-translational modifications and are therefore immediately active after their synthesis. As a result, the cells that produce such bacteriocins have developed means of protection against them which often involve transport systems. In this and our previous work, we constructed different mutants deleted in the genes involved in the transport functions, thus covering all the supposed components of this transport system, using Listeria innocua ATCC 33090 as the indicator strain to assess the activity of externalized EntDD14. We also assessed the self-resistance of the WT and all its engineered derivative mutants against EntDD14, provided extracellularly, in order to evaluate their self-resistance. The results obtained highlight that the ABC transporter constituted by the DdG, H, I, and J proteins contributes to EntDD14 export as well as resistance to an external supply of EntDD14. Our results also have established the essential role of the DdE and DdF proteins as primary transporters dedicated to the externalization of EntDD14. Moreover, the in silico data showed that DdE and DdF appear to assemble in a formation that forms an essential channel for the exit of EntDD14. This channel DdEF may interact with the ABC transporter DdGHIJ in order to control the flow of bacteriocin across the membrane, although the nature of this interaction remains to be elucidated.

Insights into Pharmacological Activities of Nicotine and 6-Hydroxy-L-nicotine, a Bacterial Nicotine Derivative: A Systematic Review.

The purported cognitive benefits associated with nicotine and its metabolites in the brain are a matter of debate. In this review, the impact of the pharmacologically active metabolite of a nicotine derivative produced by bacteria named 6-hydroxy-L-nicotine (6HLN) on memory, oxidative stress, and the activity of the cholinergic system in the brain was examined. A search in the PubMed, Science Direct, Web of Science, and Google Scholar databases, limiting entries to those published between 1992 and 2023, was conducted. The search focused specifically on articles about nicotine metabolites, memory, oxidative stress, and cholinergic system activity, as well as enzymes or pathways related to nicotine degradation in bacteria. The preliminary search resulted in 696 articles, and following the application of exclusion criteria, 212 articles were deemed eligible for inclusion. This review focuses on experimental studies supporting nicotine catabolism in bacteria, and the chemical and pharmacological activities of nicotine and its metabolite 6HLN.

Pinus halepensis Essential Oil Ameliorates Aß1-42-Induced Brain Injury by Diminishing Anxiety, Oxidative Stress, and Neuroinflammation in Rats.

The Pinus L. genus comprises around 250 species, being popular worldwide for their medicinal and aromatic properties. The present study aimed to evaluate the P. halepensis Mill. essential oil (PNO) in an Alzheimer's disease (AD) environment as an anxiolytic and antidepressant agent. The AD-like symptoms were induced in Wistar male rats by intracerebroventricular administration of amyloid beta1-42 (Aß1-42), and PNO (1% and 3%) was delivered to Aß1-42 pre-treated rats via inhalation route for 21 consecutive days, 30 min before behavioral assessments. The obtained results indicate PNO's potential to relieve anxious-depressive features and to restore redox imbalance in the rats exhibiting AD-like neuropsychiatric impairments. Moreover, PNO presented beneficial effects against neuroinflammation and neuroapoptosis in the Aß1-42 rat AD model.

Structure of Lacticaseicin 30 and Its Engineered Variants Revealed an Interplay between the N-Terminal and C-Terminal Regions in the Activity against Gram-Negative Bacteria.

Lacticaseicin 30 is one of the five bacteriocins produced by the Gram-positive Lacticaseibacillus paracasei CNCM I-5369. This 111 amino acid bacteriocin is noteworthy for being active against Gram-negative bacilli including Escherichia coli strains resistant to colistin. Prediction of the lacticaseicin 30 structure using the Alphafold2 pipeline revealed a largely helical structure including five helix segments, which was confirmed by circular dichroism. To identify the structural requirements of the lacticaseicin 30 activity directed against Gram-negative bacilli, a series of variants, either shortened or containing point mutations, was heterologously produced in Escherichia coli and assayed for their antibacterial activity against a panel of target strains including Gram-negative bacteria and the Gram-positive Listeria innocua. Lacticaseicin 30 variants comprising either the N-terminal region (amino acids 1 to 39) or the central and C-terminal regions (amino acids 40 to 111) were prepared. Furthermore, mutations were introduced by site-directed mutagenesis to obtain ten bacteriocin variants E6G, T7P, E32G, T33P, T52P, D57G, A74P, Y78S, Y93S and A97P. Compared to lacticaseicin 30, the anti-Gram-negative activity of the N-terminal peptide and variants E32G, T33P and D57G remained almost unchanged, while that of the C-terminal peptide and variants E6G, T7P, T52P, A74P, Y78S, Y93S and A97P was significantly altered. Finally, the N-terminal region was further shortened to keep only the first 20 amino acid part that was predicted to include the first helix. The anti-Gram-negative activity of this truncated peptide was completely abolished. Overall, this study shows that activity of lacticaseicin 30, one of the rare Gram-positive bacteriocins inhibiting Gram-negative bacteria, requires at least two helices in the N-terminal region and that the C-terminal region carries amino acids playing a role in modulation of the activity. Taken together, these data will help to design forthcoming variants of lacticaseicin 30 as promising therapeutic agents to treat infections caused by Gram-negative bacilli.

Complete Genome Sequences of Two Closely Related Paenarthrobacter nicotinovorans Strains.

Paenarthrobacter nicotinovorans is a soil bacterium that uses the pyridine pathway to degrade nicotine. The genome of strain ATCC 49919 is composed of a ~4.3-Mbp chromosome and a ~165-kbp plasmid. The second strain, termed here nic-, is a cured derivative lacking the plasmid and not able to degrade nicotine.

Conifer Essential Oils Reversed Amyloid Beta1-42 Action by Modulating BDNF and ARC Expression in The Rat Hippocampus.

BACKGROUND: The conifer species Pinus halepensis (Pinaceae) and Tetraclinis articulata (Cupressaceae) are widely used in traditional medicine due to their beneficial health properties. OBJECTIVE: This study aimed to investigate the mechanisms by which P. halepensis and T. articulata essential oils (1% and 3%) could exhibit neuroprotective effects in an Alzheimer's disease (AD) rat model, induced by intracerebroventricular (i.c.v.) administration of amyloid beta1-42 (Aß1-42). METHODS: The essential oils were administered by inhalation to the AD rat model, once daily, for 21 days. DNA fragmentation was assessed through a Cell Death Detection ELISA kit. Brainderived neurotrophic factor (BDNF), activity-regulated cytoskeleton-associated protein (ARC), and interleukin-1ß (IL-1ß) gene expressions were determined by RT-qPCR analysis, while BDNF and ARC protein expressions were assessed using immunohistochemistry technique. RESULTS: Our data showed that both essential oils substantially attenuated memory impairments, with P. halepensis mainly stimulating ARC expression and T. articulata mostly enhancing BDNF expression. Also, the inhalation of essential oils reduced IL-1ß expression and induced positive effects against DNA fragmentation associated with Aß1-42-induced toxicity, further contributing to the cognitive improvement in the rats with the AD-like model Conclusion: Our findings provide further evidence that these essential oils and their chemical constituents could be natural agents of therapeutic interest against Aß1-42-induced neurotoxicity.

Time-Dependent Analysis of Paenarthrobacter nicotinovorans pAO1 Nicotine-Related Proteome.

Paenarthrobacter nicotinovorans is a soil Gram-positive nicotine-degrading microorganism (NDM) that harbors a 165 kb pAO1 catabolic megaplasmid. The nicotine catabolic genes on pAO1 have been sequenced, but not all the details on the regulation and interplay of this pathway with the general metabolism of the cell are available. To address this issue at the protein level, a time-based shotgun proteomics study was performed. P. nicotinovorans was grown in the presence or absence of nicotine, and the cells were harvested at three different time intervals: 7, 10, and 24 h after inoculation. The cells were lysed, separated on SDS-PAGE, and digested by in-gel digestion using trypsin, and the resulting peptide mixture was analyzed using nanoliquid chromatography tandem mass spectrometry. We found an extensive number of proteins that are both plasmidal- and chromosomal-encoded and that work together in the energetic metabolism via the Krebs cycle and nicotine pathway. These data provide insight into the adaptation of the bacterial cells to the nicotine metabolic intermediates and could serve as a basis for future attempts to genetically engineer the pAO1-encoded catabolic pathway for increased bioremediation efficiency or for the production of valuable chemicals. The mass-spectrometry-based proteomics data have been deposited to the PRIDE partner repository with the data set identifier PXD012577.

A beginner's guideline for low-cost 3D printing of macromolecules usable for teaching and demonstration.

The structure and function of biomolecules relationship is the hallmark of biochemistry, molecular biology, and life sciences in general. Physical models of macromolecules give students the possibility to manipulate these structures in three dimensions, developing a sense of spatiality and a better understanding of key aspects such as atom size and shape, bond lengths and symmetry. Several molecular model systems were developed specifically to represent particular classes or groups of molecules and hence lack the flexibility of a universal solution. Three-dimensional printing could nevertheless provide such a universal solution, as it can be used to create physical models of biomolecular structures based on the teacher's or demonstrator's needs and requirements. Here, insulin was used as a model molecule and several depiction and printing parameters were tested in order to highlight the technical limitations of the approach. In the end, a set of settings that worked is provided which could serve as a starting point for anyone wishing to print his or her own custom macromolecular model on the cheap.

Anxiolytic, Promnesic, Anti-Acetylcholinesterase and Antioxidant Effects of Cotinine and 6-Hydroxy-L-Nicotine in Scopolamine-Induced Zebrafish (Danio rerio) Model of Alzheimer's Disease.

Cotinine (COT) and 6-hydroxy-L-nicotine (6HLN) are two nicotinic derivatives that possess cognitive-improving abilities and antioxidant properties in different rodent models of Alzheimer's disease (AD), eluding the side-effects of nicotine (NIC), the parent molecule. In the current study, we evaluated the impact of COT and 6HLN on memory deterioration, anxiety, and oxidative stress in the scopolamine (SCOP)-induced zebrafish model of AD. For this, COT and 6HLN were acutely administered by immersion to zebrafish that were treated with SCOP before testing. The memory performances were assessed in Y-maze and object discrimination (NOR) tasks, while the anxiety-like behavior was evaluated in the novel tank diving test (NTT). The acetylcholinesterase (AChE) activity and oxidative stress were measured from brain samples. The RT-qPCR analysis was used to evaluate the npy, egr1, bdnf, and nrf2a gene expression. Our data indicated that both COT and 6HLN attenuated the SCOP-induced anxiety-like behavior and memory impairment and reduced the oxidative stress and AChE activity in the brain of zebrafish. Finally, RT-qPCR analysis indicated that COT and 6HLN increased the npy, egr1, bdnf, and nrf2a gene expression. Therefore, COT and 6HLN could be used as tools for improving AD conditions.

Cotinine and 6-Hydroxy-L-Nicotine Reverses Memory Deficits and Reduces Oxidative Stress in Aß25-35-Induced Rat Model of Alzheimer's Disease.

The nicotinic derivatives, cotinine (COT), and 6-hydroxy-L-nicotine (6HLN), showed promising cognitive-improving effects without exhibiting the nicotine's side-effects. Here, we investigated the impact of COT and 6HLN on memory impairment and the oxidative stress in the Aß25-35-induced rat model of Alzheimer's disease (AD). COT and 6HLN were chronically administered to Aß25-35-treated rats, and their memory performances were assessed using in vivo tasks (Y-maze, novel object recognition, and radial arm maze). By using in silico tools, we attempted to associate the behavioral outcomes with the calculated binding potential of these nicotinic compounds in the allosteric sites of α7 and α4ß2 subtypes of the nicotinic acetylcholine receptors (nAChRs). The oxidative status and acetylcholinesterase (AChE) activity were determined from the hippocampal tissues. RT-qPCR assessed bdnf, arc, and il-1ß mRNA levels. Our data revealed that COT and 6HLN could bind to α7 and α4ß2 nAChRs with similar or even higher affinity than nicotine. Consequently, the treatment exhibited a pro-cognitive, antioxidant, and anti-AChE profile in the Aß25-35-induced rat model of AD. Finally, RT-qPCR analysis revealed that COT and 6HLN positively modulated the bdnf, arc, and il-1ß genes expression. Therefore, these nicotinic derivatives that act on the cholinergic system might represent a promising choice to ameliorate AD conditions.

A Critical Review of Bottom-Up Proteomics: The Good, the Bad, and the Future of this Field.

Proteomics is the field of study that includes the analysis of proteins, from either a basic science prospective or a clinical one. Proteins can be investigated for their abundance, variety of proteoforms due to post-translational modifications (PTMs), and their stable or transient protein-protein interactions. This can be especially beneficial in the clinical setting when studying proteins involved in different diseases and conditions. Here, we aim to describe a bottom-up proteomics workflow from sample preparation to data analysis, including all of its benefits and pitfalls. We also describe potential improvements in this type of proteomics workflow for the future.

A soil bacterial catabolic pathway on the move: Transfer of nicotine catabolic genes between Arthrobacter genus megaplasmids and invasion by mobile elements.

The 165,137 bp plasmid pAO1 of Paenarthrobacter nicotinovorans carries the genes of a nicotine catabolic pathway. The genes are organized into several gene modules responsible for the catabolism of L- and D-nicotine to nicotine blue, alpha-ketoglutarate and succinate. Various modules of these genes have been shown to be present in gram-positive (Gram?) soil bacteria. The presence of the identical pAO1 nic-genes on the 288,370 bp plasmid pZXY21 of Arthrobacter sp. ZXY2 (96 percent to 100 percent at the nucleotide level) permitted the identification of the limits of this DNA fragment. At the 5' end of the nic-genes are located the ORFs of two predicted integrases of the tyrosine recombinase family with conserved R, H, R and Y catalytic residues and that of a small transposase with a predicted leucine zipper motive. They are related to Tn554A, Tn554B and Tn554C of Staphylococcus aureus and suggest that the entire nic-genes DNA fragment represents a large catabolic transposon. Surprisingly the nic-genes on pZXY21 were found to be interspersed by mobile elements encoding transposases of various IS families. Insertion of these IS elements disrupts nicotine degradation and divide the nic-genes DNA into potentially new transposons. This finding may illustrate how nicotine catabolic genes can be mobilized and spread by horizontal gene transfer to other soil bacteria.

Mass Spectrometry- and Computational Structural Biology-Based Investigation of Proteins and Peptides.

Recent developments of mass spectrometry (MS) allow us to identify, estimate, and characterize proteins and protein complexes. At the same time, structural biology helps to determine the protein structure and its structure-function relationship. Together, they aid to understand the protein structure, property, function, protein-complex assembly, protein-protein interaction, and dynamics. The present chapter is organized with illustrative results to demonstrate how experimental mass spectrometry can be combined with computational structural biology for detailed studies of protein's structures. We have used tumor differentiation factor protein/peptide as ligand and Hsp70/Hsp90 as receptor protein as examples to study ligand-protein interaction. To investigate possible protein conformation, we will describe two proteins-lysozyme and myoglobin. As an application of MS-based assignment of disulfide bridges, the case of the spider venom polypeptide Phα1ß will also be discussed.

Exploration of Nicotine Metabolism in Paenarthrobacter nicotinovorans pAO1 by Microbial Proteomics.

Proteomics, or the large-scale study of proteins, is a post-genomics field that, together with transcriptomics and metabolomics, has moved the study of bacteria to a new era based on system-wide understanding of bacterial metabolic and regulatory networks. The study of bacterial proteins or microbial proteomics has found a wide array of applications in many fields of microbiology, from food, clinical, and industrial microbiology to microbial ecology and physiology. The current chapter makes a brief technical introduction into the available approaches for the large-scale study of bacterial proteins using mass-spectrometry. Furthermore, the advantages and disadvantages of using bacteria for proteomics studies are indicated as well as several example studies where MS-based bacterial proteomics had a fundamental role in deciphering the scientific question. Finally, the proteomics study of nicotine catabolism in Paenarthrobacter nicotinovorans pAO1 using nanoLC-MS/MS is given as an in-depth example for possible applications of microbial proteomics.The nicotine degradation pathway functioning in Paenarthrobacter nicotinovorans is encoded by the catabolic megaplasmid pAO1 that contains about 40 nicotine-related genes making out the nic-gens cluster. Despite the promising biotechnological potential for the production of green-chemicals, only half of the nic-genes have been experimentally linked to nicotine. In an attempt to systematically identify all the proteins involved in nicotine degradation, a gel-based proteomics approach was used to identify a total of 801 proteins when Paenarthrobacter nicotinovorans was grown on three carbon sources: citrate, nicotine and nicotine and citrate. The differences in protein abundance showed that the bacterium is able to switch between deamination and demethylation in the lower nicotine pathway based on the available C source. Several pAO1 putative genes including a hypothetical polyketide cyclase have been shown to have a nicotine-dependent expression and we hypothesize that the polyketide cyclase would hydrolyze the N1-C6 bond from the pyridine ring with the formation of alpha-keto-glutaramate. Two chromosomal proteins, a malate dehydrogenase, and a D-3-phosphoglycerate dehydrogenase were shown to be strongly upregulated when nicotine was the sole carbon source and could be related to the production of the alpha-keto-glutaramate by the polyketide cyclase.

Proteomics based analysis of the nicotine catabolism in Paenarthrobacter nicotinovorans pAO1.

Paenarthrobacter nicotinovorans is a nicotine-degrading microorganism that shows a promising biotechnological potential for the production of compounds with industrial and pharmaceutical importance. Its ability to use nicotine was linked to the presence of the catabolic megaplasmid pAO1. Although extensive work has been performed on the molecular biology of nicotine degradation in this bacterium, only half of the genes putatively involved have been experimentally linked to nicotine. In the current approach, we used nanoLC-MS/MS to identify a total of 801 proteins grouped in 511 non-redundant protein clusters when P. nicotinovorans was grown on citrate, nicotine and nicotine and citrate as the only carbon sources. The differences in protein abundance showed that deamination is preferred when citrate is present. Several putative genes from the pAO1 megaplasmid have been shown to have a nicotine-dependent expression, including a hypothetical polyketide cyclase. We hypothesize that the enzyme would hydrolyze the N1-C6 bond from the pyridine ring with the formation of α-keto- glutaramate. Two chromosomally-encoded proteins, a malate dehydrogenase, and a D-3-phosphoglycerate dehydrogenase were shown to be strongly up-regulated when nicotine was the sole carbon source and could be related to the production the α-keto-glutarate. The data have been deposited to the ProteomeXchange with identifier PXD008756.

Ameliorative effects of Matricaria chamomilla L. hydroalcoholic extract on scopolamine-induced memory impairment in rats: A behavioral and molecular study.

BACKGROUND: Matricaria chamomilla L. is a medicinal herb traditionally used as the anti-inflammatory, antimicrobial, antiviral, anxiolytic and antidepressant agent. Nevertheless, supporting evidence demonstrated its memory enhancing activity and antioxidant properties. PURPOSE: To investigate the effects of the hydroalcoholic extract of M. chamomilla L. on memory processes in a scopolamine-induced a rat model of amnesia and to reveal its underlying mechanism of action. METHODS: The hydroalcoholic extract (25 and 75 mg/kg) was intraperitoneally administered to rats once daily for 7 days, and scopolamine (0.7 mg/kg) was injected 30 min before the behavioral testing to induce memory impairment. The phytochemical composition of the extract was quantified by HPLC/DAD analysis. Y-maze and radial arm-maze tests were employed for memory assessing. Acetylcholinesterase activity was measured in the rat hippocampus. Superoxide dismutase, glutathione peroxidase, and catalase specific activities along with the total content of reduced glutathione and protein carbonyl and malondialdehyde levels were also measured in the rat hippocampus. qRT-PCR was used to quantify BDNF mRNA and IL1ß mRNA expression in the rat hippocampus. RESULTS: We first identified the chlorogenic acid, apigenin-7-glucoside, rutin, cynaroside, luteolin, apigenin and derivatives of apigenin-7-glucoside as the extract major components. Furthermore, we showed that the extract reversed the scopolamine-induced decreasing of the spontaneous alternation in the Y-maze test and the scopolamine-induced increasing of the working and reference memory errors in the radial arm maze test. Also, the scopolamine-induced alteration of the acetylcholinesterase activity and the oxidant-antioxidant balance in the rat hippocampus was recovered by the treatment with the extract. Finally, we demonstrated that the extract restored the scopolamine-decreased BDNF expression and increased IL1ß expression in the rat hippocampus. CONCLUSION: These findings suggest that the extract could be a potent neuropharmacological agent against amnesia via modulating cholinergic activity, neuroinflammation and promoting antioxidant action in the rat hippocampus.

Structural Characterization and Disulfide Assignment of Spider Peptide Phα1ß by Mass Spectrometry.

Native Phα1ß is a peptide purified from the venom of the armed spider Phoneutria nigriventer that has been shown to have an extensive analgesic effect with fewer side effects than ω-conotoxin MVIIA. Recombinant Phα1ß mimics the effects of the native Phα1ß. Because of this, it has been suggested that Phα1ß may have potential to be used as a therapeutic for controlling persistent pathological pain. The amino acid sequence of Phα1ß is known; however, the exact structure and disulfide arrangement has yet to be determined. Determination of the disulfide linkages and exact structure could greatly assist in pharmacological analysis and determination of why this peptide is such an effective analgesic. Here, we used biochemical and mass spectrometry approaches to determine the disulfide linkages present in the recombinant Phα1ß peptide. Using a combination of MALDI-MS, direct infusion ESI-MS, and nanoLC-MS/MS analysis of the undigested recombinant Phα1ß peptide and digested with AspN, trypsin, or AspN/trypsin, we were able to identify and confirm all six disulfide linkages present in the peptide as Cys1-2, Cys3-4, Cys5-6, Cys7-8, Cys9-10, and Cys11-12. These results were also partially confirmed in the native Phα1ß peptide. These experiments provide essential structural information about Phα1ß and may assist in providing insight into the peptide's analgesic effect with very low side effects. Graphical Abstract ᅟ.

Lactuca capensis reverses memory deficits in Aß1-42-induced an animal model of Alzheimer's disease.

We investigated the neuropharmacological effects of the methanolic extract from Lactuca capensis Thunb. leaves (100 and 200 mg/kg) for 21 days on memory impairment in an Alzheimer's disease (AD) rat model produced by direct intraventricular delivery of amyloid-ß1-42 (Aß1-42). Behavioural assays such as Y-maze and radial arm maze test were used for assessing memory performance. Aß1-42 decreased cognitive performance in the behavioural tests which were ameliorated by pre-treatment with the methanolic extract. Acetylcholinesterase activity and oxidant-antioxidant balance in the rat hippocampus were abnormally altered by Aß1-42 treatment while these deficits were recovered by pre-treatment with the methanolic extract. In addition, rats were given Aß1-42 exhibited in the hippocampus decreased brain-derived neurotrophic factor (BDNF) mRNA copy number and increased IL-1ß mRNA copy number which was reversed by the methanolic extract administration. These findings suggest that the methanolic extract could be a potent neuropharmacological agent against dementia via modulating cholinergic activity, increasing of BDNF levels and promoting antioxidant action in the rat hippocampus.

Cognitive-enhancing and antioxidant activities of the aqueous extract from Markhamia tomentosa (Benth.) K. Schum. stem bark in a rat model of scopolamine.

BACKGROUND: Plants of the genus Markhamia have been traditionally used by different tribes in various parts of West African countries, including Cameroun. Markhamia tomentosa (Benth.) K. Schum. (Bignoniaceae) is used as an antimalarial, anti-inflammatory, analgesic, antioxidant and anti-Alzheimer agent. The current study was undertaken in order to investigate its anti-amnesic and antioxidant potential on scopolamine-induced cognitive impairment and to determine its possible mechanism of action. METHODS: Rats were pretreated with the aqueous extract (50 and 200 mg/kg, p.o.), for 10 days, and received a single injection of scopolamine (0.7 mg/kg, i.p.) before training in Y-maze and radial arm-maze tests. The biochemical parameters in the rat hippocampus were also assessed to explore oxidative status. Statistical analyses were performed using two-way ANOVA followed by Tukey's post hoc test. F values for which p < 0.05 were regarded as statistically significant. RESULTS: In the scopolamine-treated rats, the aqueous extract improved memory in behavioral tests and decreased the oxidative stress in the rat hippocampus. Also, the aqueous extract exhibited anti-acetylcholinesterase activity. CONCLUSIONS: These results suggest that the aqueous extract ameliorates scopolamine-induced spatial memory impairment by attenuation of the oxidative stress in the rat hippocampus.