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Article ; Online: Exploring NAD

Jeje, Olamide / Otun, Sarah / Aloke, Chinyere / Achilonu, Ikechukwu

2024 Volume 220, Page(s) 84–98

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2024-01-03
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2024.01.002
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Article ; Online: Coping with the ESKAPE pathogens: Evolving strategies, challenges and future prospects.

Aloke, Chinyere / Achilonu, Ikechukwu

Microbial pathogenesis

2022 Volume 175, Page(s) 105963

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Anti-Bacterial Agents/chemistry ; Staphylococcal Infections ; Klebsiella pneumoniae ; Enterobacter ; Adaptation, Psychological
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2022-12-27
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2022.105963
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Article ; Online: Exploiting Copaifera salikounda compounds as treatment against diabetes: An insight into their potential targets from a computational perspective.

Aloke, Chinyere / Iwuchukwu, Emmanuel Amarachi / Achilonu, Ikechukwu

Computational biology and chemistry

2023 Volume 104, Page(s) 107851

Abstract: 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 ...

Abstract	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.
MeSH term(s)	Molecular Docking Simulation ; Ligands ; PPAR alpha ; Diabetes Mellitus ; Hypoglycemic Agents/pharmacology ; Plant Extracts ; Fabaceae
Chemical Substances	Ligands ; PPAR alpha ; Hypoglycemic Agents ; Plant Extracts
Language	English
Publishing date	2023-03-22
Publishing country	England
Document type	Journal Article
ISSN	1476-928X
ISSN (online)	1476-928X
DOI	10.1016/j.compbiolchem.2023.107851
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Article: 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.

Kanu C, Shedrach / Aloke, Chinyere / Elom I, Nwabueze / Eleazu O, Chinedum

Journal of Ayurveda and integrative medicine

2022 Volume 13, Issue 4, Page(s) 100656

Abstract: 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 ... ...

Abstract	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 × 10 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.
Language	English
Publishing date	2022-11-16
Publishing country	United States
Document type	Journal Article
ISSN	0975-9476
ISSN	0975-9476
DOI	10.1016/j.jaim.2022.100656
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Article ; Online: Biophysical description of Bromosulfophthalein interaction with the 28-kDa glutathione transferase from Schistosoma japonicum.

Pooe, Kagiso / Thulo, Monare / Makumbe, Hattie / Akumadu, Blessing / Otun, Oluwatobin / Aloke, Chinyere / Achilonu, Ikechukwu

Molecular and biochemical parasitology

2022 Volume 252, Page(s) 111524

Abstract: 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 ... ...

Abstract	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 IC
MeSH term(s)	Animals ; Binding Sites ; Calorimetry ; Glutathione/metabolism ; Glutathione Transferase/antagonists & inhibitors ; Schistosoma japonicum/drug effects ; Schistosoma japonicum/enzymology ; Sulfobromophthalein/pharmacology
Chemical Substances	Glutathione (GAN16C9B8O) ; Glutathione Transferase (EC 2.5.1.18) ; Sulfobromophthalein (0C2P5QKL36)
Language	English
Publishing date	2022-10-03
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	756166-0
ISSN	1872-9428 ; 0166-6851
ISSN (online)	1872-9428
ISSN	0166-6851
DOI	10.1016/j.molbiopara.2022.111524
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Article ; Online: Expression, Purification, and Biophysical Characterization of Klebsiella Pneumoniae Nicotinate Nucleotide Adenylyltransferase.

Daya, Tasvi / Jeje, Olamide / Maake, Reabetswe / Aloke, Chinyere / Khoza, Thandeka / Achilonu, Ikechukwu

The protein journal

2022 Volume 41, Issue 1, Page(s) 141–156

Abstract: 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 ... ...

Abstract	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 Ni
MeSH term(s)	Crystallography, X-Ray ; Escherichia coli/metabolism ; Humans ; Klebsiella pneumoniae/enzymology ; Klebsiella pneumoniae/genetics ; Nicotinamide-Nucleotide Adenylyltransferase/chemistry ; Nicotinamide-Nucleotide Adenylyltransferase/metabolism
Chemical Substances	Nicotinamide-Nucleotide Adenylyltransferase (EC 2.7.7.1) ; nicotinic acid mononucleotide adenylyltransferase (EC 2.7.7.18)
Language	English
Publishing date	2022-01-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2143071-8
ISSN	1875-8355 ; 1572-3887
ISSN (online)	1875-8355
ISSN	1572-3887
DOI	10.1007/s10930-021-10037-2
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Article ; Online: Phytochemicals from medicinal plants from African forests with potentials in rheumatoid arthritis management.

Aloke, Chinyere / Ohanenye, Ikenna C / Aja, Patrick M / Ejike, Chukwunonso E C C

The Journal of pharmacy and pharmacology

2022 Volume 74, Issue 9, Page(s) 1205–1219

Abstract: 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, ... ...

Abstract	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'.
MeSH term(s)	Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/metabolism ; Forests ; Humans ; Inflammation ; Phytochemicals/pharmacology ; Phytochemicals/therapeutic use ; Plants, Medicinal/chemistry
Chemical Substances	Phytochemicals
Language	English
Publishing date	2022-07-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	3107-0
ISSN	2042-7158 ; 0022-3573 ; 0373-1022
ISSN (online)	2042-7158
ISSN	0022-3573 ; 0373-1022
DOI	10.1093/jpp/rgac043
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Article ; Online: A world free of malaria: It is time for Africa to actively champion and take leadership of elimination and eradication strategies.

Egwu, Chinedu Ogbonnia / Aloke, Chinyere / Chukwu, Jennifer / Agwu, Anthony / Alum, Esther / Tsamesidis, Ioannis / Aja, Patrick M / Offor, Christian E / Obasi, Nwogo Ajuka

African health sciences

2023 Volume 22, Issue 4, Page(s) 627–640

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Leadership ; Malaria/epidemiology ; Malaria/prevention & control ; Africa/epidemiology
Language	English
Publishing date	2023-04-06
Publishing country	Uganda
Document type	Journal Article
ZDB-ID	2240308-5
ISSN	1729-0503 ; 1680-6905
ISSN (online)	1729-0503
ISSN	1680-6905
DOI	10.4314/ahs.v22i4.68
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Article ; Online: Engineering a Pseudo-26-kDa

Padi, Neo / Akumadu, Blessing Oluebube / Faerch, Olga / Aloke, Chinyere / Meyer, Vanessa / Achilonu, Ikechukwu

Biomolecules

2021 Volume 11, Issue 12

Abstract: Glutathione transferases (GSTs) are the main detoxification enzymes in schistosomes. These parasitic enzymes tend to be upregulated during drug treatment, ... ...

Abstract	Glutathione transferases (GSTs) are the main detoxification enzymes in schistosomes. These parasitic enzymes tend to be upregulated during drug treatment, with
MeSH term(s)	Animals ; Enzyme Stability ; Escherichia coli/genetics ; Escherichia coli/growth & development ; Glutathione Transferase/chemistry ; Glutathione Transferase/genetics ; Glutathione Transferase/metabolism ; Helminth Proteins/chemistry ; Helminth Proteins/genetics ; Helminth Proteins/metabolism ; Models, Molecular ; Protein Engineering/methods ; Protein Structure, Secondary ; Recombinant Proteins/chemistry ; Recombinant Proteins/metabolism ; Schistosoma haematobium/enzymology ; Schistosoma haematobium/genetics ; Sulfobromophthalein/pharmacology
Chemical Substances	Helminth Proteins ; Recombinant Proteins ; Sulfobromophthalein (0C2P5QKL36) ; Glutathione Transferase (EC 2.5.1.18)
Language	English
Publishing date	2021-12-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom11121844
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Article ; Online: Medicinal plants

Aloke Chinyere / Egwu Chinedu Ogbonnia / Adelusi Oluwasola Abayomi / Chinaka Nnamdi / Kanu Shedrach Chidiebere / Ogbodo Peace Nzubuchukwu / Akumadu Blessing Oluebube / Achilonu Ikechukwu

Current Issues in Pharmacy and Medical Sciences, Vol 36, Iss 2, Pp 65-

A promising source of anti-diabetic agents in sub-Sahara Africa

2023 Volume 76

Abstract: The rising burden of Diabetes mellitus (DM) globally and particularly in sub-Sahara Africa calls for alternative treatment solutions. This is because the currently available drugs for its management are limited due to undesirable adverse effects and high ...

Abstract	The rising burden of Diabetes mellitus (DM) globally and particularly in sub-Sahara Africa calls for alternative treatment solutions. This is because the currently available drugs for its management are limited due to undesirable adverse effects and high cost. Thus, this review explores diabetes and summarizes its treatment options, focusing mainly on medicinal plants therapy. Information on twenty-five selected medicinal plants from sub-Sahara Africa having hypoglycemic and anti-diabetic potentials was obtained via electronic search of major databases, such as Pubmed/Medline, Scopus, Google Scholar and web of science. Predominant bioactive compounds found in these plants include tannins, carpaine, terpenoids, hexadecenoic acid, luteolin, saponins, glycosides, rutin, quercetin, vindoline and kaempferol. Robust evidence indicates that these medicinal plants and their bioactive components exert their antidiabetic potentials via different mechanisms, including: regeneration of pancreatic β-cell and insulin secretion; inhibition of α-amylase, inhibition of intestinal glucose absorption and liver glucose production; antioxidative stress; limitation of glycogen degradation and gluconeogenesis; anti-inflammatory, immunoregulatory. DM imposes a tremendous burden in the region, and its prevalence is not abating; thus the rich flora of the region with known hypoglycemic and antidiabetic efficacy could be explored as a complementary therapy in its management.
Keywords	medicinal plants ; sub-sahara africa ; hypoglycemia ; diabetes mellitus ; conventional drugs ; Medicine ; R
Subject code	580
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Sciendo
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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