In silico exploration of anti-prostate cancer compounds from differential expressed genes.

Prostate cancer (PCa) is a complex and biologically diverse disease with no curative treatment options at present. This study aims to utilize computational methods to explore potential anti-PCa compounds based on differentially expressed genes (DEGs), with the goal of identifying novel therapeutic indications or repurposing existing drugs. The methods employed in this study include DEGs-to-drug prediction, pharmacokinetics prediction, target prediction, network analysis, and molecular docking. The findings revealed a total of 79 upregulated DEGs and 110 downregulated DEGs in PCa, which were used to identify drug compounds capable of reversing the dysregulated conditions (dexverapamil, emetine, parthenolide, dobutamine, terfenadine, pimozide, mefloquine, ellipticine, and trifluoperazine) at a threshold probability of 20% on several molecular targets, such as serotonin receptors 2a/2b/2c, HERG protein, adrenergic receptors alpha-1a/2a, dopamine D3 receptor, inducible nitric oxide synthase (iNOS), epidermal growth factor receptor erbB1 (EGFR), tyrosine-protein kinases, and C-C chemokine receptor type 5 (CCR5). Molecular docking analysis revealed that terfenadine binding to inducible nitric oxide synthase (-7.833 kcal.mol-1) and pimozide binding to HERG (-7.636 kcal.mol-1). Overall, binding energy ΔGbind (Total) at 0 ns was lower than that of 100 ns for both the Terfenadine-iNOS complex (-101.707 to -103.302 kcal.mol-1) and Ellipticine-TOPIIα complex (-42.229 to -58.780 kcal.mol-1). In conclusion, this study provides insight on molecular targets that could possibly contribute to the molecular mechanisms underlying PCa. Further preclinical and clinical studies are required to validate the therapeutic effectiveness of these identified drugs in PCa disease.

Effect of Dalbergiella welwitschi alkaloid-rich extracts on neuroprotective in streptozotocin-induced diabetic rats.

The neuroprotective ability of alkaloid-rich leaf extract of Dalbergiella welwitschii in streptozotocin-induced type 2 diabetic rats were investigated in this study. Dalbergiella welwitshii leaf alkaloid-rich extract was obtained using standard procedure. Streptozotocin was injected into the experimental animals intraperitoneally at a dose of 45 mg/mg body weight. Prior to this, the animals were given 20% (w/v) fructose for one week. The animals were grouped into five (n = 8), comprising of normal control (NC), diabetic control (DC), diabetic rats treated with low (50 mg/mg body weight) and high (100 mg/kg body weight) doses of Dalbergiella welwitschii alkaloid-rich leaf extracts (i.e., DWL and DWH respectively) and 200 mg/kg body weight of metformin (MET). The animals were sacrificed on the 21st day, blood and brain tissue were harvested and used for the determination of neurotransmitters, cholinesterase, some ATP activities, oxidative stress biomarkers and histological examination. The results show that diabetic rats placed on DWL, DWH and MET significantly (p < 0.05) reduced cholinergic, elevated some ATPase activities and ameliorated oxidative stress biomarkers. These were supported by the histological examination by improving neuroprotective effects in diabetic rats administered DWL, DWH and MET. Hence, it can be presumed that DWL and DWH could be beneficial in treating diabetic neurodegenerative diseases.

In Silico Comparison of Bioactive Compounds Characterized from Azadirachta indica with an FDA-Approved Drug against Schistosomal Agents: New Insight into Schistosomiasis Treatment.

The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly difficult to tackle schistosomiasis with praziquantel, a drug known to be effective against all Schistosoma species, due to reports of reduced efficacy and resistance. Therefore, this study seeks to investigate the antischistosomal potential of phytochemicals from Azadirachta indica against proteins that have been implicated as druggable targets for the treatment of schistosomiasis using computational techniques. In this study, sixty-three (63) previously isolated and characterized phytochemicals from A. indica were identified from the literature and retrieved from the PubChem database. In silico screening was conducted to assess the inhibitory potential of these phytochemicals against three receptors (Schistosoma mansoni Thioredoxin glutathione reductase, dihydroorotate dehydrogenase, and Arginase) that may serve as therapeutic targets for schistosomiasis treatment. Molecular docking, ADMET prediction, ligand interaction, MMGBSA, and molecular dynamics simulation of the hit compounds were conducted using the Schrodinger molecular drug discovery suite. The results show that Andrographolide possesses a satisfactory pharmacokinetic profile, does not violate the Lipinski rule of five, binds with favourable affinity with the receptors, and interacts with key amino acids at the active site. Importantly, its interaction with dihydroorotate dehydrogenase, an enzyme responsible for the catalysis of the de novo pyrimidine nucleotide biosynthetic pathway rate-limiting step, shows a glide score and MMGBSA of -10.19 and -45.75 Kcal/mol, respectively. In addition, the MD simulation shows its stability at the active site of the receptor. Overall, this study revealed that Andrographolide from Azadirachta indica could serve as a potential lead compound for the development of an anti-schistosomal drug.

Benzimidazole compound abrogates SARS-COV-2 receptor-binding domain (RBD)/ACE2 interaction In vitro.

The development of clinically actionable pharmaceuticals against coronavirus disease (COVID-19); an infectious disease caused by the SARS-CoV-2 virus is very important for ending the pandemic. Coronavirus spike glycoprotein (GP)-Receptor Binding Domain (RBD) and its interaction with host receptor angiotensin converting enzyme 2 (ACE2) is one of the most structurally understood but therapeutically untapped aspect of COVID-19 pathogenesis. Binding interface based on previous x-ray structure of RBD/ACE2 were virtually screened to identify fragments with high-binding score from 12,000 chemical building blocks. The hit compound was subjected to fingerprint-based similarity search to identify compounds within the FDA-approved drug library containing the same core scaffold. Identified compounds were then re-docked into of RBD/ACE2. The best ranked compound was validated for RBD/ACE2 inhibition using commercial kit. Molecular dynamics simulation was conducted to provide further insight into the mechanism of inhibition. From the original 12000 chemical building blocks, benzimidazole (BAZ) scaffold was identified. Fingerprint-based similarity search of the FDA-approved drug library for BAZ-containing compounds identified 12 drugs with the benzimidazole-like substructure. When these compounds were re-docked into GP/ACE2 interface, the consensus docking identified bazedoxifene as the hit. In vitro RBD/ACE2 inhibition kinetics showed micromolar IC50 value (1.237 µM) in the presence of bazedoxifene. Molecular dynamics simulation of RBD/ACE2 in the presence BAZ resulted in loss of contact and specific hydrogen-bond interaction required for RBD/ACE2 stability. Taken together, these findings identified benzimidazole scaffold as a building block for developing novel RBD/ACE2 complex inhibitor and provided mechanistic basis for the use of bazedoxifene as a repurposable drug for the treatment of COVID-19 acting at RBD/ACE2 interface.

Computational and Preclinical Prediction of the Antimicrobial Properties of an Agent Isolated from Monodora myristica: A Novel DNA Gyrase Inhibitor.

The African nutmeg (Monodora myristica) is a medically useful plant. We, herein, aimed to critically examine whether bioactive compounds identified in the extracted oil of Monodora myristica could act as antimicrobial agents. To this end, we employed the Schrödinger platform as the computational tool to screen bioactive compounds identified in the oil of Monodora myristica. Our lead compound displayed the highest potency when compared with levofloxacin based on its binding affinity. The hit molecule was further subjected to an Absorption, Distribution, Metabolism, Excretion (ADME) prediction, and a Molecular Dynamics (MD) simulation was carried out on molecules with PubChem IDs 529885 and 175002 and on three standards (levofloxacin, cephalexin, and novobiocin). The MD analysis results demonstrated that two molecules are highly compact when compared to the native protein; thereby, this suggests that they could affect the protein on a structural and a functional level. The employed computational approach demonstrates that conformational changes occur in DNA gyrase after the binding of inhibitors; thereby, this resulted in structural and functional changes. These findings expand our knowledge on the inhibition of bacterial DNA gyrase and could pave the way for the discovery of new drugs for the treatment of multi-resistant bacterial infections.

Profiling the Antidiabetic Potential of Compounds Identified from Fractionated Extracts of Entada africana toward Glucokinase Stimulation: Computational Insight.

Glucokinase plays an important role in regulating the blood glucose level and serves as an essential therapeutic target in type 2 diabetes management. Entada africana is a medicinal plant and highly rich source of bioactive ligands with the potency to develop new target drugs for glucokinase such as diabetes and obesity. Therefore, the study explored a computational approach to predict identified compounds from Entada africana following its intermolecular interactions with the allosteric binding site of the enzymes. We retrieved the three-dimensional (3D) crystal structure of glucokinase (PDB ID: 4L3Q) from the online protein data bank and prepared it using the Maestro 13.5, Schrödinger Suite 2022-3. The compounds identified were subjected to ADME, docking analysis, pharmacophore modeling, and molecular simulation. The results show the binding potential of the identified ligands to the amino acid residues, thereby suggesting an interaction of the amino acids with the ligand at the binding site of the glucokinase activator through conventional chemical bonds such as hydrogen bonds and hydrophobic interactions. The compatibility of the molecules was highly observed when compared with the standard ligand, thereby leading to structural and functional changes. Therefore, the bioactive components from Entada africana could be a good driver of glucokinase, thereby paving the way for the discovery of therapeutic drugs for the treatment of diabetes and its related complications.

Ameliorative effect of flavonoid-rich extracts from Gongronema latifolium against diabetic cardiomyopathy via serpin A3 and socs3-a in streptozocin treated rats.

INTRODUCTION: The present study access the effect of the flavonoid-rich extract from Gongronema latifolium against cardiomyopathy streptozotocin-induced diabetic rats. MATERIALS AND METHODS: The flavonoid-rich extract from G. latifolium leaf (FREGL) was prepared using a standard method. Diabetes was induced by a single intraperitoneal (i.p.) injection of streptozotocin. The experimental animals were divided into five groups as non-diabetic rats, diabetic control, diabetic rats administered low and high doses of FREGL (13 and 26 mg/kg), and metformin-glibenclamide orally for 21 days. Hence, the experimental animals were sacrificed; blood and heart were harvested to determine diverse biochemical parameters, including the gene expressions of serpin A3 and socs3-a as well as histological examination. RESULTS: The results demonstrated that FREGL significantly (p < 0.05) reduced fasting blood glucose, total cholesterol, low density lipoprotein (LDL), triglyceride (TG), lipid peroxidation levels, as well as the activities of lactate dehydrogenase and creatine kinase-MB, including the relative gene expressions of serpin A3 and Socs3-A in diabetic rats. Also, diabetic rats that received different doses of FREGL showed a substantial rise in insulin and high density lipoprotein (HDL) levels, antioxidant enzyme activities, as well as, normal histoarchitecture of the heart tissues. CONCLUSION: Therefore, FREGL may be beneficial in alleviating diabetic cardiomyopathy.

Hepatoprotective potential of flavonoid-rich extracts from Gongronema latifolium benth leaf in type 2 diabetic rats via fetuin-A and tumor necrosis factor-alpha.

BACKGROUND: This study assessed the hepatoprotective potential of flavonoid-rich extracts from Gongronema latifolium Benth on diabetes-induced type 2 rats via Fetuin-A and tumor necrosis factor-alpha (TnF-α). METHODS: In a standard procedure, the flavonoid-rich extract was prepared. For experimental rats, streptozotocin was injected intraperitoneally (45 mg/kg body weight) to induce diabetes mellitus. Following this, rats were given 5% of glucose water for 24 h. Hence, the animals were randomly divided into five groups of ten rats each, consisting of non-diabetic rats, diabetic controls, diabetic rats treated with low and high doses of flavonoid rich-extracts from Gongronema latifolium leaf (FREGL) (13 and 26 mg/kg, respectively), and diabetic rats treated with 200 mg/kg of metformin glibenclamide orally for 3 weeks. Afterwards, the animals were sacrificed, blood and liver were harvested to evaluate different biochemical parameters, hepatic gene expressions and histological examinations. RESULTS: The results revealed that FREGL (especially at the low dose) significantly (p < 0.05) reduced alanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphate (ALP) activities, lipid peroxidation level, as well as relative gene expressions of fetuin-A and TNF-α in diabetic rats. Furthermore, diabetic rats given various doses of FREGL showed an increase in antioxidant enzymes and hexokinase activity, as well as glucose transporters (GLUT 2 and GLUT 4), and glycogen levels. In addition, histoarchitecture of the liver of diabetic rats administered FREGL (especially at the low dose) was also ameliorated. CONCLUSION: Hence, FREGL (particularly at a low dose) may play a substantial role in mitigating the hepatopathy complication associated with diabetes mellitus.

Nephroprotective and anti-inflammatory potential of aqueous extract from Persea americana seeds against cadmium-induced nephrotoxicity in Wistar rats.

Cadmium is a toxic metal and poses a high environmental risk to animals and humans, alike. It is thus pertinent to search for medicinal plants in protecting against cadmium toxicity. This study aims at investigating the ability of aqueous extract of Persea americana seeds (AEPA) in ameliorating the toxic effects of cadmium in the kidneys of cadmium-exposed Wistar rats. Male Wistar rats were grouped into five, of six animals each. Different groups of animals received normal saline (control group), 200 mg/kg body weight AEPA, 400 mg/kg AEPA, and standard drug, Livolin Forte, respectively. A last group of animals was left untreated. To induce toxicity, all animals, except the control group, were exposed to cadmium (200 mg/L, as CdCl2) in their main drinking water for 21 days. Biochemical analysis of serum kidney markers, oxidative stress and antioxidant status, as well as anti-inflammatory activities, was done using standard methods and kits. In silico analysis was performed on phytochemicals reported to be abundant in AEPA. Treatment with 400 mg/kg AEPA significantly reversed (P ≤ 0.05) the adverse effect of cadmium on serum creatinine, urea, uric acid and blood urea nitrogen, and restored (P ≤ 0.05) antioxidant status, evidenced by its significant effect on superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, reduced glutathione, and lipid peroxidation activities. AEPA, at 400 mg/kg also exhibited significant anti-inflammatory effects, which was shown by reduced interleukin-2 and tumour necrosis factor α activities. Molecular docking of phytochemicals with the selected protein target also confirmed the therapeutic potential of AEPA. The study concluded that aqueous extract of AEPA protects against cadmium-induced kidney toxicity and inflammation.

Aframomum melegueta secondary metabolites exhibit polypharmacology against SARS-CoV-2 drug targets: in vitro validation of furin inhibition.

COVID-19 pandemic is currently decimating the world's most advanced technologies and largest economies and making its way to the continent of Africa. Weak medical infrastructure and over-reliance on medical aids may eventually predict worse outcomes in Africa. To reverse this trend, Africa must re-evaluate the only area with strategic advantage; phytotherapy. One of the many plants with previous antiviral potency is against RNA viruses is Aframomum melegueta. In this study, one hundred (100) A. melegueta secondary metabolites have been mined and computational evaluated for inhibition of host furin, and SARS-COV-2 targets including 3C-like proteinase (Mpro /3CLpro ), 2'-O-ribose methyltransferase (nsp16) and surface glycoprotein/ACE2 receptor interface. Silica-gel column partitioning of A. melegueta fruit/seed resulted in 6 fractions tested against furin activity. Diarylheptanoid (Letestuianin A), phenylpropanoid (4-Cinnamoyl-3-hydroxy-spiro[furan-5,2'-(1'H)-indene]-1',2,3'(2'H,5H)-trione), flavonoids (Quercetin, Apigenin and Tectochrysin) have been identified as high-binding compounds to SARS-COV-2 targets in a polypharmacology manner. Di-ethyl-ether (IC50 = 0.03 mg/L), acetone (IC50 = 1.564 mg/L), ethyl-acetate (IC50 = 0.382 mg/L) and methanol (IC50 = 0.438 mg/L) fractions demonstrated the best inhibition in kinetic assay while DEF, ASF and MEF completely inhibited furin-recognition sequence containing Ebola virus-pre-glycoprotein. In conclusion, A. melegueta and its secondary metabolites have potential for addressing the therapeutic needs of African population during the COVID-19 pandemic.

Gongronema latifolium Benth. leaf extract attenuates diabetes-induced neuropathy via inhibition of cognitive, oxidative stress and inflammatory response.

BACKGROUND: Gongronema latifolium (G. latifolium) Benth. leaves are traditionally used to treat diabetes mellitus (DM) and other diseases in Nigeria and West Africa. This study was performed to evaluate the neuroprotective effect of aqueous extract of G. latifolium leaf against DM. Antidiabetic activity of G. latifolium extracts (6.36, 12.72 and 25.44 mg kg-1 , i.p.) was determined in alloxan-induced diabetic rats. Fasting blood glucose level and oxidative stress markers catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), and nitric oxide (NO) levels were measured. Cognitive biomarkers acetylcholinesterase (AChE), butyrylcholinesterase (BChE), dopamine (DOPA), serotonin, epinephrine and norepinephrine and cyclooxygenase (COX-2) were measured in the brain of controls and of G. latifolium-treated diabetic rats. RESULTS: Administration of G. latifolium leaf extract to diabetic rats significantly restored the alterations in the levels of fasting blood glucose (FBG). The MDA and NO levels were significantly reduced with an improvement in CAT, SOD, and GPx activity in the kidneys and brains of diabetic rats treated with G. latifolium. Gongronema latifolium also significantly decreased the levels of AChE, BChE, DOPA, serotonin, epinephrine, and nor-epinephrine in diabetic rats. G. latifolium effectively ameliorated COX-2 in diabetic rats. CONCLUSION: This study showed that leaf extract of G. latifolium improved antioxidant defense against oxidative stress. It displays a neuroprotective effect resulting in the modulation of brain neurotransmitters, which could be considered as a promising treatment therapy. © 2020 Society of Chemical Industry.

In vitro antioxidant and inhibitory activities of polyphenolic-rich extracts of Syzygium cumini (Linn) Skeels leaf on two important enzymes relevant to type II diabetes mellitus.

In this study, the effect of free and bound polyphenolic-rich extract of Syzygium cumini (Linn) Skeels leaf on antioxidant as well as α-amylase and α-glucosidase activities were determined using in vitro model. Polyphenolic-rich extract of Syzygium cumini (Linn) Skeels leaf was prepared accordingly and the capability of the extract to inhibit antioxidants as typified by ferric reducing power (FRAP) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) among other free radicals scavenging abilities were quantified spectrophotometrically, added to this, the activities of (α-amylase and α-glucosidase were also assessed. The bound phenolic extract exhibited more in vitro antioxidant properties as represented by their high radicals scavenging ability in all the free radicals evaluated. Also, the polyphenolic-rich extracts inhibited α-amylase and α-glucosidase, with bound phenolics showing significant (p<0.05) increase in a dose-dependent manner than free phenolics. Therefore, this study suggests the use of Syzygium cumini leaf as a nutraceutical in the management/ control of type II diabetes mellitus patients.

Ocimum gratissimum Linn. Leaves reduce the key enzymes activities relevant to erectile dysfunction in isolated penile and testicular tissues of rats.

BACKGROUND: Ocimum gratissimum L. is a medicinal plant widely grown in tropical and subtropical regions with the leaf decoction usually taken in folk medicine to enhance erectile performance in men although the probable mechanism of actions remains undetermined. This study examined the inhibitory potentials of Ocimum gratissimum leaves on some key enzymes associated with erectile dysfunction in penile and testicular tissues of the rat. METHODS: Inhibitory effect of aqueous extract (1:10 w/v) of O. gratissimum leaves on the activities of phosphodiesterase-5 (PDE-5), arginase, angiotensin I -converting enzyme (ACE), and acetylcholinesterase (AChE) in penile and testicular tissues were assessed. Also, the extract was investigated for ferric reducing antioxidant property(FRAP) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) radical scavenging abilities. RESULTS: The extract showed higher PDE-5 (IC50 = 43.19 µg/mL), ACE (IC50 = 44.23 µg/mL), AChE (IC50 = 55.51 µg/mL) and arginase (IC50 = 46.12 µg/mL) inhibitory activity in the penile tissue than PDE-5 (IC50 = 44.67 µg/mL), ACE (IC50 = 53.99 µg/mL), AChE (IC50 = 60.03 µg/mL) and arginase (IC50 = 49.12 µg/mL) inhibitory activity in the testicular tissue homogenate. Furthermore, the extract scavenged free radicals and in a dose-dependent manner. CONCLUSION: The enzyme activities displayed might be associated with the bioactive compounds present in the extract which could possibly explain its use in the management of erectile dysfunction (ED).

Effect of Zingiber officinale on some biochemical parameters and cytogenic analysis in lead-induced toxicity in experimental rats.

Exposure to toxic elements is greatly unavoidable in our daily activities due to several routes of coming in contact with these elements. Thus lead (Pb), is one of the major causes of health hazard in human. In this study, evaluation of Zingiber officinale as mitigating measure against Pb induced biochemical and cytogenic toxicity in albino rats was investigated. Experimental rats were grouped into five with five animals per group, group I serves as control and groups 2-5 were induced intraperitoneal with lead acetate dissolved in distilled water at 3 mg/kg body weight whereas group 3-5 were orally administered with 200 mg/kg vitamin C, 200 mg/kg, and 100 mg/kg of Z. officinale, respectively for 7 d. The obtained results show that aspartate aminotransferase (AST), alkaline phosphatase (ALP), lipid peroxidation, urea, creatinine, bilirubin, and gamma-glutamyl transferase (GGT) were significantly increased (p < 0.05) and catalase (CAT) were reduced progressively in Pb alone induced rats. Hematological parameters showed a progressive reduction (p < 0.05) in lead acetate alone rats. There were significant changes in micronuclei (MN), chromosomal aberrations (CA) frequency, and oxidative damages in the bone marrow cells from lead acetate alone induced rats, although, mitotic index scores in these cells were reduced gradually (p < 0.05). The altered parameters were significantly reversed toward the levels observed in normal control rats administered with vitamin C and aqueous extract of Z. officinale. Hence, these results suggest that Z. officinale roots might contain therapeutic potential that can ameliorate the hazard effect of lead acetate poison.

Antihyperglycaemia and related gene expressions of aqueous extract of Gongronema latifolium leaf in alloxan-induced diabetic rats.

Context: Gongronema latifolium Benth (Asclepiadaceae) has been highly utilized in controlling diabetes mellitus traditionally in the eastern part of Nigeria. Objectives: Antihyperglycaemic and related gene expressions of aqueous extract of Gongronema latifolium leaf in alloxan-induced diabetic rats. Materials and methods: Forty-eight female Wistar rats were induced intraperitoneally using alloxan (150 mg/kg body weight). The rats were separated into six groups (n = 8) as follows: non-diabetic control, diabetic control, diabetic rats administered 5 mg/kg body weight of metformin, and diabetic rats administered 6.36, 12.72 and 25.44 mg/kg body weight (ethnobotanical doses) of G. latifolium orally daily. On the 14th day, the animals were sacrificed and different antihyperglycaemic parameters were evaluated as well as its related gene expressions. Results: Diabetic rats administered three doses of aqueous extract of G. latifolium significantly (p < 0.05) lowered the fasting blood glucose, glycated haemoglobin, serum lipid profiles, lipid peroxidation (5.62-1.2 µ/mg protein) levels, as well as gene expression of glucose-6-phosphatase in alloxan-induced diabetic rats. There was a significant (p < 0.05) increase in the liver glycogen content (16.23-112.5 mg glucose/2 g), antioxidant enzymes activities, glucose transporter (GLUT-2 and GLUT-4) levels and relative gene expression of hexokinase in diabetic rats administered different doses of aqueous extract of G. latifolium. Discussion and conclusions: It can be deduced that the aqueous extract of G. latifolium leaf at these doses may be useful in managing diabetes mellitus and its associated complications. Therefore, this extract may be a potent antidiabetic agent in clinical therapy in the future.

Structural Studies of Predicted Ligand Binding Sites and Molecular Docking Analysis of Slc2a4 as a Therapeutic Target for the Treatment of Cancer.

Presently, many studies have focused on exploring in silico approaches in the identification and development of alternative therapy for the treatment and management of cancer. Solute carrier family-2-member-4-gene (Slc2a4) which encodes glucose transporter 4 protein (GLUT4), has been identified as a promising therapeutic target for cancer. Though Slc2a4 is known to play a major regulatory role in the pathophysiology of type 2 diabetes, emerging evidence suggests that successful pharmacological inhibition of this protein may lead to the development of a novel drug candidate for the treatment of cancer. In this study, Slc2a4 protein sequence was retrieved and analysed using in silico approaches, and we identified seven putative antimicrobial peptides (AMPs; RAB1-RAB7) as anti-cancer. The structures of the protein and AMPs were modelled using I-TASSER server, and the overall quality of the Slc2a4 model was validated using PROCHECK. Subsequently, the probable motifs and active site of the protein were forecasted. Also, the molecular interaction between the AMPs and Slc2a4 was ascertained using PatchDock. The result revealed that, all the AMPs are good Slc2a4 inhibitors with RAB1 having the highest binding affinity of 12,392 and binding energy of -39.13 kcal/mol. Hence, this study reveals that all the generated AMPs can serve as therapeutic drug in treating cancer by inhibiting Slc2a4 which is responsible for the production of energy for cancer cells during angiogenesis. This is the first report on AMPs as inhibitors of Slc2a4 for the treatment of cancer.

Proteomic Analysis of Differentially-Expressed Proteins in the Liver of Streptozotocin-Induced Diabetic Rats Treated with Parkia biglobosa Protein Isolate.

Protein isolate from Parkia biglobosa seeds is believed to possess excellent anti-diabetic properties. The purpose of this study was to identify differentially expressed proteins in liver of streptozotocin-induced diabetic rats treated with Parkia biglobosa seeds protein isolate (PBPi). In this study, total proteins extracted from rat liver were separated on one-dimensional SDS polyacrylamide gel (1D SDS-PAGE) and stained with Coomassie brilliant blue (CBB) to visualize protein bands. We observed that protein bands in the region of 10-15 kDa were altered by the different treatments; these bands were selected and excised for in-gel digestion and peptide extraction followed by nLC-MS, MALDI-TOF MS, and LIFT MS/MS. A database search with the Mascot algorithm positively identified four differentially expressed proteins. These proteins are known to be responsible for diverse biological functions within various organs and tissues. The present result gives insight and understanding into possible molecular mechanisms by which streptozotocin causes various alterations in proteins found in the liver of diabetic rats and the possible modulatory role of PBPi in the management of streptozotocin-induced diabetes.

Protective Effects of Parkia biglobosa Protein Isolate on Streptozotocin-Induced Hepatic Damage and Oxidative Stress in Diabetic Male Rats.

This study sought to investigate the possible protective role of Parkia biglobosa seed protein isolate (PBPi) against streptozotocin-induced hepatic damage and oxidative stress in diabetic male rats. Prior to animal experiments, a HPLC fingerprint of PBPi was recorded. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight). Diabetic rats were orally treated daily with PBPi (200 or 400 mg/kg body weight) or insulin (5 U/kg, i.p.) for 28 days. The degree of protection was evaluated using biochemical parameters such as malondialdehyde (MDA) levels, serum transaminases (ALT and AST), total protein, total glutathione (Total GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and interleukin-6 (IL-6) activities. Histology of liver sections was also performed. The HPLC fingerprint of PBPi revealed eleven distinct peaks; PBPi at tested doses significantly attenuates STZ-induced elevated levels of serum IL-6, ALT and AST; and hepatic TBARS levels. Hepatic antioxidants (Total GSH, GST, SOD, CAT) as well as total protein were markedly restored in a dose-dependent manner. Histopathological results strongly support the protective role of PBPi. These results suggest PBPi could confer protection by ameliorating hepatic damage and oxidative stress caused by STZ in animal model possibly via its anti-inflammatory and antioxidant properties.

The Effects of Piper Guineense versus Sesamum Indicum Aqueous Extracts on Lipid Metabolism and Antioxidants in Hypercholesterolemic Rats.

BACKGROUND: Piper guineense (PG) and Sesamum indicum (SI) have been shown to be rich sources of antioxidants and other health benefits; hence, we evaluated the impact of its consumption in hypercholesterolemic model on lipid metabolism. METHODS: Forty-eight animals were divided into eight groups of six rats each. Rats were given cholesterol (40 mg/0.3ml), PG and SI extract (100 and 200 mg/kg), and Questran (0.26 g/kg) orally, five times a week for 28 days. Lipid profile, hepatic antioxidant status, biomarkers of liver toxicity, and tissue histopathology were examined. Data were analyzed using one-way ANOVA and P<0.05 were considered statistically significant. RESULTS: Cholesterol feeding caused 100% gain in weight, significantly increased AST, LPO (P=0.41 and 0.002) but significantly decreased SOD (P=0.003) compared to control. CHPG(1)/(2) and CHSI(1)/(2) caused a significant decrease (P=0.01, 0.005, 0.003, and 0.023) in cholesterol-induced body-weight gain and decreased serum total cholesterol by 20-30% compared to untreated-hypercholesterolemic rats. Triglyceride and LDL-c decreased with extract administration and specifically HDL-c increased significantly (P<0.001) by CHSI(1) compared to untreated-hypercholesterol rats. Furthermore, an increase in HDL-c was higher (P=0.04 and 0.002) by SI compared to PG at both doses. CONCLUSION: These results indicate that PG and SI exerts a hypolipidemic effect, reduces cholesterol intake induced body weight gain, and increases the body's antioxidant defense system in experimental hypercholesterolemia.

Telemedicine as a tool to prevent multi-drug resistant tuberculosis in poor resource settings: Lessons from Nigeria.

Background: This mini review aims to provide an overview of the role of telemedicine in preventing multi-drug resistant tuberculosis (MDR-TB) in Nigeria. The specific objectives include examining the potential benefits of telemedicine, identifying the challenges associated with its implementation, and highlighting the importance of addressing infrastructure limitations and data privacy concerns. Methods: This minireview is based on a comprehensive analysis of existing literature, including scholarly articles, and reports,. A systematic search was conducted using electronic databases, such as PubMed and Google Scholar, to identify relevant publications related to telemedicine and MDR-TB prevention in Nigeria. The selected articles were assessed for their relevance, and key findings were synthesized to provide an overview of the role of telemedicine in addressing the challenges of MDR-TB in Nigeria. Results: The review demonstrates that telemedicine has the potential to significantly contribute to MDR-TB prevention efforts in Nigeria. The benefits of telemedicine include improved access to specialized care, enhanced patient adherence to treatment, and potential cost savings. However, challenges such as infrastructure limitations and data privacy concerns need to be addressed for successful implementation. Integrating telemedicine into the healthcare system has the potential to strengthen MDR-TB prevention, particularly in underserved areas, including within Nigeria. Specifically, the integration of telemedicine into the healthcare system can enhance access to specialized care, improve patient adherence, and potentially reduce costs associated with MDR-TB management. Conclusions: Addressing infrastructure challenges, ensuring data privacy and security, and fostering trust among healthcare providers and patients are critical for successful implementation of telemedicine. Further research and policy frameworks are needed to guide the effective implementation and scale-up of telemedicine in MDR-TB prevention efforts in Nigeria.