Exploring NAD+ metabolism and NNAT: Insights from structure, function, and computational modeling.

Nicotinamide Adenine Dinucleotide (NAD+), a coenzyme, is ubiquitously distributed and serves crucial functions in diverse biological processes, encompassing redox reactions, energy metabolism, and cellular signalling. This review article explores the intricate realm of NAD + metabolism, with a particular emphasis on the complex relationship between its structure, function, and the pivotal enzyme, Nicotinate Nucleotide Adenylyltransferase (NNAT), also known as nicotinate mononucleotide adenylyltransferase (NaMNAT), in the process of its biosynthesis. Our findings indicate that NAD + biosynthesis in humans and bacteria occurs via the same de novo synthesis route and the pyridine ring salvage pathway. Maintaining NAD homeostasis in bacteria is imperative, as most bacterial species cannot get NAD+ from their surroundings. However, due to lower sequence identity and structurally distant relationship of bacteria, including E. faecium and K. pneumonia, to its human counterpart, inhibiting NNAT, an indispensable enzyme implicated in NAD + biosynthesis, is a viable alternative in curtailing infections orchestrated by E. faecium and K. pneumonia. By merging empirical and computational discoveries and connecting the intricate NAD + metabolism network with NNAT's crucial role, it becomes clear that the synergistic effect of these insights may lead to a more profound understanding of the coenzyme's function and its potential applications in the fields of therapeutics and biotechnology.

Exploiting Copaifera salikounda compounds as treatment against diabetes: An insight into their potential targets from a computational perspective.

Accumulating evidence has shown that medicinal plants have been exploited for treatment purposes since time immemorial. Thus, this study investigated the mitigating potentials of the ligands; n-hexadecanoic acid, 9-octadecenoic acid and octadecanoic acid from Copaifera salikounda seed pond extract reported to have antidiabetic potentials in our previous study using computational techniques. Fatty acid-binding protein 4 (FABP4) and peroxisome proliferator-activated receptor alpha (PPARα) were identified as potential receptors. Both molecular docking and Estimated ΔGbind revealed that each ligand exhibited high binding affinity to the respective proteins; this is quite sufficient to be termed favourable. A critical examination of the type and the nature of binding interactions and energy contributions have identified Arg106, Arg126 and Tyr128 in FABP4 and Gln277, Ser280, Tyr314, His440 and Tyr464 in PPARα as consistently being responsible for the binding interactions and stabilizations of each ligand to the individual proteins. The establishment of hydrogen bonding type of interaction and activity between the carboxylic acid moieties of these ligands and these crucial/unique residues goes further to buttress our assertion. A general study of the conformational state of these protein via RMSF and PCA plots goes further validate the observed structural trends wherein the presence of ligands induced seemly structural rigidity. In depth structural stability investigations went further to reveal that the 3D structures of these protein didn't deviate from it known native conformational stable state when bound with these ligands. Our findings indicate that the ligands have considerable inhibitory action against FABP4 and PPARα corroborating the reported antidiabetic potential of the extract.

Assessment of the Antimalarial Treatment Failure in Ebonyi State, Southeast Nigeria.

The fight against malaria is a continuum as the epidemic is not abating. For proper deployment of tools in the fight against malaria, an assessment of the situation is necessary. This work assessed the level of antimalarial drug treatment failure in Ebonyi State, Nigeria. Both survey and in vitro analyses were adopted. The survey was used to obtain qualitative information from both the malaria subjects and the pharmacies where antimalarial drugs are sourced. The results from the survey were complemented by an in vitro assay of the level of active pharmaceutical ingredients (APIs) in the commonly used artemisinin combination in Nigeria; artemether/lumefantrine. Results from the survey revealed that artemisinin combination therapies (ACTs) remain the mainstay in the treatment of malaria, even though other non-artemisinin drugs are still used. It also revealed that many patients still self-medicate, although, this may not be connected to the treatment failure seen among some malaria subjects. The in vitro assay showed that ACT contains the right quantity of APIs. Further surveillance is, therefore, necessary to understand the real cause of treatment failure among malaria subjects in Nigeria.

Combating Lassa Fever in West African Sub-Region: Progress, Challenges, and Future Perspectives.

Lassa fever (LF) is a rodent-borne disease that threatens human health in the sub-region of West Africa where the zoonotic host of Lassa virus (LASV) is predominant. Currently, treatment options for LF are limited and since no preventive vaccine is approved for its infectivity, there is a high mortality rate in endemic areas. This narrative review explores the transmission, pathogenicity of LASV, advances, and challenges of different treatment options. Our findings indicate that genetic diversity among the different strains of LASV and their ability to circumvent the immune system poses a critical challenge to the development of LASV vaccines/therapeutics. Thus, understanding the biochemistry, physiology and genetic polymorphism of LASV, mechanism of evading host immunity are essential for development of effective LASV vaccines/therapeutics to combat this lethal viral disease. The LASV nucleoprotein (NP) is a novel target for therapeutics as it functions significantly in several aspects of the viral life cycle. Consequently, LASV NP inhibitors could be employed as effective therapeutics as they will potentially inhibit LASV replication. Effective preventive control measures, vaccine development, target validation, and repurposing of existing drugs, such as ribavirin, using activity or in silico-based and computational bioinformatics, would aid in the development of novel drugs for LF management.

Coping with the ESKAPE pathogens: Evolving strategies, challenges and future prospects.

Globally, the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the major cause of nosocomial infections. These pathogens are multidrug resistant, and their negative impacts have brought serious health challenges and economic burden on many countries worldwide. Thus, this narrative review exploits different emerging alternative therapeutic strategies including combination antibiotics, antimicrobial peptides ((AMPs), bacteriophage and photodynamic therapies used in the treatment of the ESKAPE pathogens, their merits, limitations, and future prospects. Our findings indicate that ESKAPE pathogens exhibit resistance to drug using different mechanisms including drug inactivation by irreversible enzyme cleavage, drug-binding site alteration, diminution in permeability of drug or drug efflux increment to reduce accumulation of drug as well as biofilms production. However, the scientific community has shown significant interest in using these novel strategies with numerous benefits although they have some limitations including but not limited to instability and toxicity of the therapeutic agents, or the host developing immune response against the therapeutic agents. Thus, comprehension of resistance mechanisms of these pathogens is necessary to further develop or modify these approaches in order to overcome these health challenges including the barriers of bacterial resistance.

Effects of co-treatment of Plasmodium berghei-infected mice with aqueous extract of Ocimum gratissimum leaves and primaquine on glucose-6-phosphate dehydrogenase activity, hematological, and antioxidant parameters.

BACKGROUND: It has been observed that most malaria patients especially G6PD-deficient patients usually experience oxidative stress and severe anemia when treated with primaquine. This calls for the need to search for a treatment option that will ameliorate these side effects. OBJECTIVE: The effect of co-treatment of malaria with aqueous extract of Ocimum gratissimum leaves (AEOGL) and primaquine on G6PD activity, antioxidant indices and hematological parameters in Plasmodium berghei-infected mice was investigated. MATERIALS AND METHODS: Thirty mice divided into six groups of five mice each were recruited for this study. Whilst Group 1 (G1) served as the negative control (group not infected with plasmodium parasite), Groups 2 to 6 (G2-G6) were inoculated intraperitoneally with 0.2 ml of 1 × 105/ml Plasmodium berghei (NK 65 strain) infected erythrocytes. G2 (parasite control) received no treatment. Groups 3,4,5 and 6 were administered 0.25 mg/kg bw of primaquine only; 100 mg/kg b. w of AEOGL +0.25 mg/kg bw of primaquine; 200 mg/kg b. w of AEOGL +0.25 mg/kg bw of primaquine; 200 mg/kg b. w of AEOGL respectively, for 14 days. RESULTS: Treatment with only primaquine gave the highest mean malaria parasite clearance (82.10 ± 0.45 percent), followed by 100 mg/kg b. w of AEOGL + Primaquine (75.59 ± 0.47 percent), 200 mg/kg b. w of AEOGL + Primaquine (67.35 ± 0.67 percent), and AEOGL alone (55 ± 0.56 percent). In comparison with the untreated malaria groups, co-treatment with AEOGL + Primaquine produced a significant (p < 0.05) increase in G6PD activity, serum ascorbate, reduced glutathione, catalase activity, and a significant (p < 0.05) decrease in malondialdehyde level in a dose-dependent pattern and also a significant (p < 0.05) rise in packed cell volume, haemoglobin, and red blood cell count, unlike treatment with only primaquine which resulted in a non-significant (P > 0.05) difference in these parameters. CONCLUSION: Co-treatment of Plasmodium berghei-infected mice with AEOGL and primaquine improved the G6PD activity, hematological parameters and antioxidant status relative to treatment with only primaquine.

Biophysical description of Bromosulfophthalein interaction with the 28-kDa glutathione transferase from Schistosoma japonicum.

Glutathione transferases (GSTs) are major detoxification enzymes vital for the survival and reproduction of schistosomes during infection in humans. Schistosoma encode two GST isoenzymes, the 26- and 28-kDa isoforms, that show different substrate specificities and cellular localisations. Bromosulfophthalein (BSP) has been identified and characterised as a potent 26-kDa Schistosoma japonicum GST (Sj26GST) inhibitor with an anthelmintic potential. This study describes the structure, function, and ligandin properties of the 28-kDa Schistosoma japonicum GST (Sj28GST) towards BSP. Enzyme kinetics show that BSP is a potent enzyme inhibitor, with a specific activity decreases from 60.4 µmol/min/mg to 0.0742 µmol/min/mg and an IC50 in the micromolar range of 0.74 µM. Far-UV circular dichroism confirmed that purified Sj28GST follows a typical GST fold, which is predominantly alpha-helical. Fluorescence spectroscopy suggests that BSP binding occurs at a site distinct from the glutathione-binding site (G-site); however, the binding does not alter the local G-site environment. Isothermal titration calorimetry studies show that the binding of BSP to Sj28GST is exergonic (∆G°= -33 kJ/mol) and enthalpically-driven, with a stoichiometry of one BSP per dimer. The stability of Sj28GST (∆G(H2O) = 4.7 kcal/mol) is notably lower than Sj26GST, owing to differences in the enzyme's dimeric interfaces. We conclude that Sj28GST shares similar biophysical characteristics with Sj26GST based on its kinetic properties and susceptibility to low concentrations of BSP. The study supports the potential benefits of re-purposing BSP as a potential drug or prodrug to mitigate the scourge of schistosomiasis.

Current Advances in the Management of Diabetes Mellitus.

Diabetes mellitus (DM) underscores a rising epidemic orchestrating critical socio-economic burden on countries globally. Different treatment options for the management of DM are evolving rapidly because the usual methods of treatment have not completely tackled the primary causes of the disease and are laden with critical adverse effects. Thus, this narrative review explores different treatment regimens in DM management and the associated challenges. A literature search for published articles on recent advances in DM management was completed with search engines including Web of Science, Pubmed/Medline, Scopus, using keywords such as DM, management of DM, and gene therapy. Our findings indicate that substantial progress has been made in DM management with promising results using different treatment regimens, including nanotechnology, gene therapy, stem cell, medical nutrition therapy, and lifestyle modification. However, a lot of challenges have been encountered using these techniques, including their optimization to ensure optimal glycemic, lipid, and blood pressure modulation to minimize complications, improvement of patients' compliance to lifestyle and pharmacologic interventions, safety, ethical issues, as well as an effective delivery system among others. In conclusion, lifestyle management alongside pharmacological approaches and the optimization of these techniques is critical for an effective and safe clinical treatment plan.

Phytochemicals from medicinal plants from African forests with potentials in rheumatoid arthritis management.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation, pain, and cartilage and bone damage. There is currently no cure for RA. It is however managed using nonsteroidal anti-inflammatory drugs, corticosteroids and disease-modifying anti-rheumatic drugs, often with severe side effects. Hidden within Africa's lush vegetation are plants with diverse medicinal properties including anti-RA potentials. This paper reviews the scientific literature for medicinal plants, growing in Africa, with reported anti-RA activities and identifies the most abundant phytochemicals deserving research attention. A search of relevant published scientific literature, using the major search engines, such as Pubmed/Medline, Scopus, Google Scholar, etc. was conducted to identify medicinal plants, growing in Africa, with anti-RA potentials. KEY FINDINGS: Twenty plants belonging to 17 families were identified. The plants are rich in phytochemicals, predominantly quercetin, rutin, catechin, kaempferol, etc., known to affect some pathways relevant in RA initiation and progression, and therefore useful in its management. SUMMARY: Targeted research is needed to unlock the potentials of medicinal plants by developing easy-to-use technologies for preparing medicines from them. Research attention should focus on how best to exploit the major phytochemicals identified in this review for the development of anti-RA 'green pharmaceuticals'.

Impact of Drug Pressure versus Limited Access to Drug in Malaria Control: The Dilemma.

Malaria burden has severe impact on the world. Several arsenals, including the use of antimalarials, are in place to curb the malaria burden. However, the application of these antimalarials has two extremes, limited access to drug and drug pressure, which may have similar impact on malaria control, leading to treatment failure through divergent mechanisms. Limited access to drugs ensures that patients do not get the right doses of the antimalarials in order to have an effective plasma concentration to kill the malaria parasites, which leads to treatment failure and overall reduction in malaria control via increased transmission rate. On the other hand, drug pressure can lead to the selection of drug resistance phenotypes in a subpopulation of the malaria parasites as they mutate in order to adapt. This also leads to a reduction in malaria control. Addressing these extremes in antimalarial application can be essential in maintaining the relevance of the conventional antimalarials in winning the war against malaria.

Expression, Purification, and Biophysical Characterization of Klebsiella Pneumoniae Nicotinate Nucleotide Adenylyltransferase.

Patients in health-care settings develop nosocomial infections due to prolonged hospital stay. The Gram negative Klebsiella pneumoniae (K. pneumoniae), is a bacterial pathogen responsible for most nosocomial infections and are resistant to most current antibiotics. Hence, there is need for identification and validation of potential protein targets for design of new generation antibiotics. One of such targets is nicotinate nucleotide adenylyltransferase, an enzyme responsible for redox metabolism. This study focuses on novel expression, purification, and biophysical characterization of NNAT from K. pneumoniae. KpNNAT was over-expressed in T7 express™ Escherichia coli using the pGEX-4 T-1 expressions system and purified to > 98% homogeneity (~ 20 mg KpNNAT/g of the wet cell) using a combination of glutathione-agarose and immobilized Ni2+ affinity chromatography. KpNNAT indirectly showed "pseudo-specific activity" of 0.30 µmol/min/mg towards ß-nicotinate mononucleotide and ATP using alcohol dehydrogenase as a secondary enzyme (in the presence of ethanol). Far-UV circular dichroism showed a ~ 38% predominantly alpha-helical and 16% ß-strand secondary structural content. The binding of ATP to KpNNAT is entropically-driven with an overall ∆G° of ‒23.8 kJ/mol and dissociation constant of 69.1 µM. Data from this study suggest that KpNNAT can be expressed in E. coli, purified to homogeneity to yield high quantities of active recombinant enzyme for downstream biophysical studies such as X-ray crystallography.

A world free of malaria: It is time for Africa to actively champion and take leadership of elimination and eradication strategies.

The global burden of malaria seems unabated. Africa carries the greatest burden accounting for over 95% of the annual cases of malaria. For the vision of a world free of malaria by Global Technical Strategy to be achieved, Africa must take up the stakeholder's role. It is therefore imperative that Africa rises up to the challenge of malaria and champion the fight against it. The fight against malaria may just be a futile or mere academic venture if Africans are not directly and fully involved. This work reviews the roles playable by Africans in order to curb the malaria in Africa and the world at large.

Engineering a Pseudo-26-kDa Schistosoma Glutathione Transferase from bovis/haematobium for Structure, Kinetics, and Ligandin Studies.

Glutathione transferases (GSTs) are the main detoxification enzymes in schistosomes. These parasitic enzymes tend to be upregulated during drug treatment, with Schistosoma haematobium being one of the species that mainly affect humans. There is a lack of complete sequence information on the closely related bovis and haematobium 26-kDa GST isoforms in any database. Consequently, we engineered a pseudo-26-kDa S. bovis/haematobium GST (Sbh26GST) to understand structure-function relations and ligandin activity towards selected potential ligands. Sbh26GST was overexpressed in Escherichia coli as an MBP-fusion protein, purified to homogeneity and catalyzed 1-chloro-2,4-dinitrobenzene-glutathione (CDNB-GSH) conjugation activity, with a specific activity of 13 µmol/min/mg. This activity decreased by ~95% in the presence of bromosulfophthalein (BSP), which showed an IC50 of 27 µM. Additionally, enzyme kinetics revealed that BSP acts as a non-competitive inhibitor relative to GSH. Spectroscopic studies affirmed that Sbh26GST adopts the canonical GST structure, which is predominantly α-helical. Further extrinsic 8-anilino-1-naphthalenesulfonate (ANS) spectroscopy illustrated that BSP, praziquantel (PZQ), and artemisinin (ART) might preferentially bind at the dimer interface or in proximity to the hydrophobic substrate-binding site of the enzyme. The Sbh26GST-BSP interaction is both enthalpically and entropically driven, with a stoichiometry of one BSP molecule per Sbh26GST dimer. Enzyme stability appeared enhanced in the presence of BSP and GSH. Induced fit ligand docking affirmed the spectroscopic, thermodynamic, and molecular modelling results. In conclusion, BSP is a potent inhibitor of Sbh26GST and could potentially be rationalized as a treatment for schistosomiasis.

Protective effects of Dialium guineense pulp on aspirin-induced gastric mucosal injury in albino rats.

The numerous challenges and detrimental effects connected with the treatment of peptic ulcers in the world today calls for alternative attention. Ethnomedicinally, Dialium guineense pulp (DAGP) has numerous pharmacological activities. This study investigated the anti-ulcer activities of Dialium guineense pulp on gastric mucosa injury induced with aspirin in albino Wistar rats. DAGP extract was orally administered at doses of 250, 500 and 1000 mg/kg bw (mg per kg of the body weight) per day for 3 or 7 days followed by 400 mg/kg bw oral aspirin administration. Ulcer indices were determined, followed by a biochemical estimation of antioxidant enzymes using gastric mucosal tissue from the stomach. Student's t-test was used to compare significant differences among groups of animals at P ≤ 0.05. The results showed that Dialium guineense pulp caused a significant decrease (P ≤ 0.05) in the ulcer index in aspirin induced rats. This decrease in ulcer index is dose dependent and 1000 mg/kg bw per day caused the highest decrease in 7 days. The results showed a significant increase (P ≤ 0.05) in lipid peroxidation and a decrease (P ≤ 0.05) in antioxidant enzymes activities in the aspirin-induced ulcerated rats. Oral administration of DAGP increased antioxidant enzymes activities and decreased injury in the gastric mucosa in ulcer induced rats. Therefore, this study showed that DAGP exhibited anti-ulcer potential and that the gastrointestinal protection may be through the scavenging action of free radicals by its constituent antioxidants. Thus, Dialium guineense pulp has ameliorative medicinal potential for the curing of gastric disorders.

Antihyperglycemic, antihyperlipidemic and hepatoprotective effects of Ficus ottoniifolia (Miq.) Miq. supplementation in alloxan-induced diabetic rats.

OBJECTIVE: Medicinal plants provide better and cheaper alternative therapy for management of several diseases compared to orthodox medicines. This study evaluated the effects of feed formulated with Ficus ottoniifolia (Miq.) Miq. (FFFO) leaves in the management of alloxan-induced diabetes mellitus (DM) in rats. MATERIALS AND METHODS: DM was induced in overnight-fasted rats by administration of alloxan monohydrate intraperitoneally. DM rats in Groups 1-3 were fed with graded FFFO while group 4 (diabetic control) and group 5 (normal control) were fed with commercial feeds (Vital-Feeds), daily for 21 days. Changes in body weight and some biochemical parameters were thereafter determined. RESULTS: Results showed significant decreases (p<0.05) in serum high-density lipoprotein (HDL) but significant increases (p<0.05) in blood glucose, serum low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC) and alanine aminotransferase (ALT) activities in DM-induced rats compared to the normal control group. Feeding with FFFO significantly increased (p<0.05) the body weight and HDL, decreased the blood glucose, serum LDL, TG and TC and attenuated ALT activities in FFFO-fed DM rats compared to the diabetic control group. CONCLUSION: This study revealed that FFFO-diet may mitigate hyperglycemia, dyslipidemia and liver-damage associated with DM.

Studies on Ethanol Extracts of Olax subscorpioidea Against Carbon Tetrachloride-Induced Hepatotoxicity in Rats.

<b>Background and Objective:</b> Liver disease orchestrated by noxious chemicals are serious health problems the world over. Traditionally, there are claims that ethanol extracts of leaves and stem barks of <i>Olax subscorpioidea</i> are used in the treatment of hepatic disorders. Thus, it investigated the impacts of ethanol extract of leaves and stem bark of <i>Olax subscorpioidea</i> against carbon tetrachloride (CCl₄)-induced liver damage in rats. <b>Materials and Methods:</b> Liver toxicity was induced by intraperitoneal injection of 2.5 mg kg¹ b.wt., of CCl₄ in experimental rats. Rats were treated with 200, 400 and 800 mg kg¹ dose ethanol leaves and stem bark of <i>Olax subscorpioidea</i>, respectively after induction of liver damage. <b>Results:</b> Obtained results showed a significant rise in the serum levels of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Malondialdehyde (MDA) and bilirubin as well as decreased Albumin (ALB), Superoxide Dismutase (SOD), Catalase (CAT), reduced Glutathione (GSH) in CCl₄-challenged rats. Treatment with the extracts attenuated serum levels of AST, ALT, ALP, MDA and bilirubin in addition to increased activities of SOD, CAT and the levels of ALB and GSH when compared to the CCl₄ group. Histopathological studies demonstrated that the extracts ameliorated liver necrosis and inflammation due to CCl₄ insult. <b>Conclusion:</b> These results concluded that ethanol extract of leaves and stem bark of <i>Olax subscorpioidea </i>may reduce hepatic oxidative injury caused by CCl₄ by its antioxidant potentials.

Sphenostylis stenocarpa Seed Extract Attenuates Dyslipidemia in Testosterone Propionate-induced Benign Prostatic Hyperplasia in Rats.

BACKGROUND AND OBJECTIVE: Benign Prostatic Hyperplasia (BPH) is a prevalent disease among older men caused by abnormal proliferation of the prostatic cells. Findings indicate an association between dyslipidemia and BPH. This study aimed at evaluating the effect of ethanol extract of Sphenostylis stenocarpa seed on the lipid profile of rats with testosterone propionate-induced BPH. MATERIALS AND METHODS: A total of 25 male Wistar rats randomized into five groups of five rats each were used. BPH was induced in the rats by subcutaneous injection of testosterone propionate in olive oil for 28 days. The test rats (after BPH induction) were treated with ethanol extract of the plant seed at doses of 200 and 400 mg kg-1 b.wt. The concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triacylglycerol were evaluated on the sera of the rats. RESULTS: The BPH control rats (model group) showed a significant (p<0.05) increase in concentrations of total cholesterol, LDL-C, triacylglycerol, with a significant decrease in HDL-C compared to the normal control. Oral administration of the seed extract to the rats significantly reversed these dyslipidemia indicators when compared to the model group. CONCLUSION: This study has shown that ethanol extract of S. stenocarpa seed ameliorated dyslipidemia in testosterone propionate-induced BPH in rats. This suggests that the plant seed may be useful in the prevention of cardiovascular disease.

Effect of acetogenin fraction of Annona muricata leaves on antioxidant status and some indices of benign prostatic hyperplasia in rats.

ABSTRACT Objectives: This work investigated the effect of acetogenin-rich fraction of Annona muricata leaves (AFAL) on antioxidant status and some markers of benign prostatic hyperplasia (BPH) in rats. Methods: BPH was experimentally induced in the rats by subcutaneous injection of testosterone propionate (TP, 3 mg/kg) for 28 consecutive days. The rats were administered orally different doses of AFAL (100 and 200 mg/kg) for 7 days. Prostate-specific antigen (PSA), prostate weight, relative prostate weight, prostate protein content and oxidative stress indices of the rats were evaluated. Results: It was observed that 200 mg/kg AFAL significantly reduced the PSA level, mean prostate weights and mean relative prostate weights of the test rats compared to the TP group, and the values were not significantly different from the normal control and group treated with a standard drug. The plant extract also significantly enhanced the antioxidant capacity of the test rats which were evidently compromised in the group that received the exogenous hormone alone. Histopathology of the prostate showed a marked recovery for the test rats after treatment with AFAL. Conclusion: Oral administration of acetogenin-rich fraction of Annona muricata leaves ameliorated TP-induced BPH in rats and significantly enhanced the antioxidant capacity of the rats.

Hesperidin protects against cadmium-induced pancreatitis by modulating insulin secretion, redox imbalance and iNOS/NF-ĸB signaling in rats.

AIM: Cadmium is a persistent ubiquitous environmental toxicant that elicits several biological defects on delicate body organs. Growing evidence suggests that cadmium (Cd) may perturb signaling pathways to induce oxidative pancreatitis. Thus, we explored whether hesperidin, a flavonone, could mitigate Cd-induced oxidative stress-mediated inflammation and pancreatitis in Wistar rats. MAIN METHODS: Forty (40) rats randomly assigned to 5 groups (n = 8) were administered normal saline or hesperidin (Hsp) followed by Cd intoxication for 28 days. KEY FINDINGS: Cadmium accumulated in the pancreas of rats, and markedly decreased insulin, pancreatic superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and glutathione (GSH) level. Cadmium considerably increased malondialdehyde (MDA), serum lipase and amylase activities. Cadmium induced pancreatic pro-inflammation via over-expression of inducible nitric oxide synthase (iNOS), nuclear factor-ĸB (NF-κB), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), along with histopathological alterations. Hesperidin prominently decreased serum amylase and lipase activities, and markedly increased insulin level, pancreatic antioxidant defense mechanism, whereas iNOS, NF-κB, IL-6 and TNF-α levels significantly decreased. Changes in histology confirmed our biochemical findings. SIGNIFICANCE: Our findings suggest that Cd induced pancreatitis via pro-inflammation and oxidative stress; Hsp, thus, protects against Cd-induced pancreatitis via attenuation of oxidative stress and proinflammatory responses in pancreas.

Elemental Composition and Associated Health Risk of Honey Obtained from Apiary Farms in Southeast Nigeria.

ABSTRACT: This study investigated the levels of lead, selenium, arsenic, iron, manganese, copper, zinc, chromium, cadmium, and nickel in honey and their potential health risks to consumers, using standard protocols. The honey samples were obtained from apiary farms at nine different locations in southeast Nigeria. They were digested at optimal conditions and analyzed using a flame atomic absorption spectrophotometer. Levels of the studied elements in the honey were found to vary relative to the sample source; however, all were below European Commission maximum permissible limits, with the exception of lead, whose level in some samples exceeded the recommended set limit. Estimated daily intakes of the elements via ingestion of the honey were all below the maximum permissible limit set by the European Food Safety Authority, with the exception of arsenic, whose values in some samples slightly exceeded the set limit. For all samples, estimated health risk values for the elements quantified were higher in children than in adults. The hazard quotient for arsenic, hence, the hazard index for the elements, indicated a significant risk (>1) for children for some of the honey samples studied. Arsenic was the major contributor to incremental lifetime cancer risk; its estimated value for children in all the honey samples exceeded the U.S. Environmental Protection Agency (EPA) threshold limit (>1.0 × 10-4); hence, the total cancer risk values for the carcinogenic elements indicated an absolute unacceptable risk level for children based on EPA threshold limit.