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.

Potential Role of Phytochemicals as Glucagon-like Peptide 1 Receptor (GLP-1R) Agonists in the Treatment of Diabetes Mellitus.

Currently, there is no known cure for diabetes. Different pharmaceutical therapies have been approved for the management of type 2 diabetes mellitus (T2DM), some are in clinical trials and they have been classified according to their route or mechanism of action. Insulin types, sulfonylureas, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, sodium-glucose cotransporter type 2 inhibitors, and incretin-dependent therapies (glucagon-like peptide-1 receptor agonists: GLP-1R, and dipeptidyl peptidase 4 inhibitors: DPP-4). Although some of the currently available drugs are effective in the management of T2DM, the side effects resulting from prolonged use of these drugs remain a serious challenge. GLP-1R agonists are currently the preferred medications to include when oral metformin alone is insufficient to manage T2DM. Medicinal plants now play prominent roles in the management of various diseases globally because they are readily available and affordable as well as having limited and transient side effects. Recently, studies have reported the ability of phytochemicals to activate glucagon-like peptide-1 receptor (GLP-1R), acting as an agonist just like the GLP-1R agonist with beneficial effects in the management of T2DM. Consequently, we propose that careful exploration of phytochemicals for the development of novel therapeutic candidates as GLP-1R agonists will be a welcome breakthrough in the management of T2DM and the co-morbidities associated with T2DM.

Nephroprotective Effect of Hibiscus Sabdariffa Leaf Flavonoid Extracts via KIM-1 and TGF-1ß Signaling Pathways in Streptozotocin-Induced Rats.

Diabetes-induced kidney damage represents a substantial health hazard, emphasizing the imperative to explore potential therapeutic interventions. This study investigates the nephroprotective activity of flavonoid-rich extracts from Hibiscus sabdariffa leaves in streptozotocin-induced diabetic rats. The flavonoid-rich extracts of H. sabdariffa leaves was obtained using a standard procedure. The animals were induced with streptozotocin and thereafter treated with both low (LDHSFL) and high doses (HDHSFL) of flavonoid-rich extracts from H. sabdariffa leaves and metformin (MET), and other groups are diabetic control (DC) and normal control (NC). The study assesses diverse renal parameters, encompassing kidney redox stress biomarkers, serum electrolyte levels, kidney inflammatory biomarkers, serum concentrations of creatinine, urea, and uric acid, kidney phosphatase activities, renal histopathology, and relative gene expressions of kidney injury molecule-1 (KIM-1) and transforming growth factor beta-1 (TGF-1ß), comparing these measurements with normal and diabetic control groups (NC and DC). The findings indicate that the use of extracts from H. sabdariffa leaves markedly (p < 0.05) enhanced renal well-being by mitigating nephropathy, as demonstrated through the adjustment of various biochemical and gene expression biomarkers, indicating a pronounced antioxidative and anti-inflammatory effect, improved kidney morphology, and mitigation of renal dysfunction. These findings suggest that H. sabdariffa leaf flavonoid extracts exhibit nephroprotective properties, presenting a potential natural therapeutic approach for the treatment of diabetic nephropathy.

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.

Attenuation of PI3K/AKT signaling pathway by Ocimum gratissimum leaf flavonoid-rich extracts in streptozotocin-induced diabetic male rats.

Diabetes is a group of medical conditions characterized by the body's inability to effectively control blood glucose levels, due to either insufficient insulin synthesis in type 1 diabetes or inadequate insulin sensitivity in type 2 diabetes. According to this research, the PI3K/AKT pathway of Ocimum gratissimum leaf flavonoid-rich extracts in streptozotocin-induced diabetic rats was studied. We purchased and used a total of forty (40) male Wistar rats for the study. We divided the animals into five (5) different groups: normal control (Group A), diabetic control (Group B), low dose (150 mg/kg body weight) of Ocimum gratissimum flavonoid-rich leaf extract (LDOGFL) (Group C), high dose (300 mg/kg body weight) of Ocimum gratissimum flavonoid-rich leaf extract (HDOGFL) (Group D), and 200 mg/kg of metformin (MET) (Group E). Streptozotocin induced all groups except Group A, which serves as the normal control group. The experiment lasted for 21 days, following which we sacrificed the animals and harvested their brains for biochemical analysis on the 22nd day. We carried out an analysis that included reduced glutathione (GSH), glutathione transferases (GST), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), along with GLUT4, MDA, pro-inflammatory cytokines, NO, neurotransmitters, cholinergic enzyme activities, cardiolipin, and the gene expression of PI3K/AKT. The obtained result indicates that the flavonoid-rich extracts of O. gratissimum significantly enhanced the levels of GSH, GST, CAT, GPx, and SOD, as well as GLUT4 and cardiolipin. The levels of GSH, GST, CAT, GPx, and SOD, as well as GLUT4 and cardiolipin, were significantly increased by gratissimum. Moreover, the extracts decrease the levels of MDA, pro-inflammatory cytokines, NO, neurotransmitters, and cholinergic enzyme activities. Additionally, the flavonoid-rich extracts of O. gratissimum significantly improved the AKT and PI3K gene expressions in diabetic rats. gratissimum had their AKT and PI3K gene expressions significantly (p < 0.05) improved. The findings indicate that O. gratissimum leaf flavonoids have the potential to treat diabetes mellitus. gratissimum leaf flavonoids possess therapeutic potential in themselves and can be applied in the management of diabetes mellitus. Although further analysis can be carried out in terms of isolating, profiling, or purifying the active compounds present in the plant's extract.

Molecular docking, MMGBSA, and ADMET studies of phytoconstituents of Ocimum gratissimum on multiple breast cancer targets.

O. gratissimum is one of the most common medicinal plants in every community in Nigeria. This plant has been presumed to be useful in the management of diseases including breast cancer, which is one the commonest cancers affecting women globally. Hence, this study aimed to computationally investigate the phytochemicals present in O. gratissimum by elucidate their binding dynamics against five selected molecular targets of breast cancer and predict their pharmacokinetics properties. Molecular docking, MMGBSA calculation and ADMET prediction were used. The results showed that isovitexin has the highest binding affinity of -9.11 kcal/mol and -9.80 kcal/mol for Human Epidermal Growth Factor Receptor 2 (HER2) and Epidermal Growth Factor Receptor (EGFR) respectively. Rosmarinic acid has the highest binding affinity of -12.15 kcal/mol for Phosphatidylinositol 3-kinase (PI3K), Nepetoidin A has the highest binding affinity of -9.14 kcal/mol for oestrogen receptor (ER), and Vitexin has the highest binding affinity of -12.90 kcal/mol for Progesterone receptor (PR). MMGBSA provided total binding energy that confirmed the stability of the complexes under physiological conditions. The ADMET profiles showed that O. gratissimum top phytochemicals identified would be safe for oral administration with no hepatoxicity. Overall, this study identified isovitexin, vitexin, rosmarinic acid, nepetoidin A and luteolin among others, as compounds that exhibit strong anti-cancer properties against breast cancer cells.

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.

Oxidative Stress, Endoplasmic Reticulum Stress and Apoptosis in the Pathology of Alzheimer's Disease.

Alzheimer's disease (AD) accounts for a major statistic among the class of neurodegenerative diseases. A number of mechanisms have been identified in its pathogenesis and progression which include the amyloid beta (Aß) aggregation, hyperphosphorylation of tau protein, oxidative stress, endoplasmic reticulum (ER) stress and apoptosis. These processes are interconnected and contribute significantly to the loss of neurons, brain mass and consequential memory loss and other cognitive difficulties. Oxidative stress in AD appears to be caused by excess of oxygen free radicals and extracellular Aß deposits that cause local inflammatory processes and activate microglia, another possible source of reactive oxygen species (ROS). ER Stress describes the accumulation of misfolded and unfolded proteins as a result of physiological and pathological stimuli including high protein demand, toxins, inflammatory cytokines, and mutant protein expression that disturbs ER homeostasis. When compared to age-matched controls, postmortem brain tissues from AD patients showed elevated levels of ER stress markers, such as PERK, eIF2α, IRE1α, the chaperone Grp78, and the downstream mediator of cell death CHOP. Apoptosis is in charge of eliminating unnecessary and undesired cells to maintain good health. However, it has been demonstrated that a malfunctioning apoptotic pathway is a major factor in the development of certain neurological and immunological problems and diseases in people, including neurodegenerative diseases. This article highlights and discussed some of the experimentally established mechanisms through which these processes lead to the development as well as the exacerbation of AD.

Ethnomedicine, phytochemistry, and pharmacological activities of Uvaria chamae P. Beauv.: A comprehensive review.

The use of medicinal plants as food and medicine has been a common practice in the world, especially in tropical African countries. One such plant in West Africa is Uvaria chamae, also known as Bush banana, renowned for its diverse ethnomedicinal applications and, more recently, for its pharmacological activities attributed to a rich array of phytochemical constituents. Various parts of the plant have been traditionally employed for the treatment of diverse health issues such as digestive disorders, fever, dysmenorrhea, cancer, wound healing, and many more. To unravel the bioactive compounds responsible for these medicinal properties, a comprehensive phytochemical analysis has been undertaken. Notable isolates include chamanetin, dichamanetin, uvaretin, and uvarinol from different parts of the plant. The pharmacological evaluation of these compounds has revealed significant anticancer and antimicrobial properties. Therefore, this review provides a thorough examination of the phytochemicals derived from Uvaria chamae, detailing their associated pharmacological activities both in vitro and in vivo. The review emphasizes the potential of Uvaria chamae as a valuable source of lead compounds for cancer chemotherapy and antimicrobial drug discovery.

Ferulic acid interventions ameliorate NDEA-CCl4-induced hepatocellular carcinoma via Nrf2 and p53 upregulation and Akt/PKB-NF-κB-TNF-α pathway downregulation in male Wistar rats.

Hepatocellular carcinoma is a prevalent form of liver cancer that is life threatening. Many chemically synthesized anti-cancer drugs have various degrees of side effects. Hence, this study investigated the effect of FEAC interventions on NDEA-CCl4-induced HCAR in male Wistar rats. HCAR was induced by intraperitoneal administration of 200 mg/kg of NDEA and 0.5 mL/kg CCl4 (as a promoter of HCAR). Following the induction of HCAR, rats were treated differently with two different doses (25 and 50 mg/kg) of FEAC. HCAR induction was confirmed by the significant elevation of serum levels of ALT, AST, and α-FP. Also elevated significantly were liver levels of Akt/PKB, NF-κB, TNF-α, MDA, GSH, and activities of GST, SOD, and CAT, while levels of liver p53 and Nrf2 were significantly lowered compared with normal rats. Treatment interventions with both 25 and 50 mg/kg of FEAC against the DEN-CCl4-induced HCAR gave comparable effects, marked by a significant reduction in the levels of serum ALT, AST and α-FP, as well as liver levels of MDA, GSH, Akt/PKB, NF-κB, TNF-α, GST, SOD, and CAT, while levels of liver p53 and Nrf2 were significantly elevated compared with normal rats. Put together and judging by the outcomes of this study, FEAC being a potent antioxidant may also be potent against chemical-induced HCAR via upregulation of p53 and Nrf2, as well as downregulation of the Akt/PKB-NF-κB pathway in rats.

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.

Syringic acid demonstrates an anti-inflammatory effect via modulation of the NF-κB-iNOS-COX-2 and JAK-STAT signaling pathways in methyl cellosolve-induced hepato-testicular inflammation in rats.

Syringic acid (SACI) is an emerging nutraceutical and antioxidant used in modern Chinese medicine. It has potential neuroprotective, anti-hyperglycemic, and anti-angiogenic properties. Methyl cellosolve (MCEL) has been reported to induce tissue inflammation in the testis, kidney, liver, and lung. This study aimed to investigate the effect and probable mechanism of action of SACI on MCEL-induced hepatic and testicular inflammation in male rats. Compared to the control group, administration of MCEL to rats significantly increased the levels of IL-6, TNF-α, iNOS, COX-2, and NF-κB in the liver and testis. Additionally, the total mRNA expressions of JAK1 (in the liver only), STAT1, and SOCS1 were significantly increased in both the liver and testis, while testicular JAK1 total mRNA levels were significantly decreased. The expression of PIAS1 protein was significantly higher in the liver and testis. Treatments with SACI at 25 (except liver iNOS), 50, and 75 mg/kg significantly decreased the levels of IL-6, TNF-α, iNOS, COX-2, and NF-κB compared to the control group. Furthermore, the total mRNA expressions of JAK1 and SOCS1 in the liver were significantly reduced by all doses of SACI investigated, while the total mRNA levels of liver and testis STAT1 were significantly reduced by 25 and 50 mg/kg of SACI only. In the testis, the mRNA level of SOCS1 was significantly reduced by all doses of SACI compared to MCEL only. Additionally, SACI (at 75 mg/kg) significantly reduced PIAS1 protein expression in the liver, while in the testis, SACI at all investigated doses significantly reduced the expression of PIAS1. In conclusion, SACI demonstrated a hepatic and testicular anti-inflammatory effect by inhibiting the MCEL-induced activation of the NF-κB and JAK-STAT signaling pathways in rats.

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.

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.

Mitochondrial defects in pancreatic beta-cell dysfunction and neurodegenerative diseases: Pathogenesis and therapeutic applications.

Mitochondria malfunction is linked to the development of ß-cell failure and a variety of neurodegenerative disorders. Pancreatic ß-cells are normally configured to detect glucose and other food secretagogues in order to adjust insulin exocytosis and maintain glucose homeostasis. As a result of the increased glucose level, mitochondria metabolites and nucleotides are produced, which operate in concert with cytosolic Ca2+ to stimulate insulin secretion. Furthermore, mitochondria are the primary generators of adenosine triphosphate (ATP), reactive oxygen species (ROS), and apoptosis regulation. Mitochondria are concentrated in synapses, and any substantial changes in synaptic mitochondria location, shape, quantity, or function might cause oxidative stress, resulting in faulty synaptic transmission, a symptom of various degenerative disorders at an early stage. However, a greater understanding of the role of mitochondria in the etiology of ß-cell dysfunction and neurodegenerative disorder should pave the way for a more effective approach to addressing these health issues. This review looks at the widespread occurrence of mitochondria depletion in humans, and its significance to mitochondria biogenesis in signaling and mitophagy. Proper understanding of the processes might be extremely beneficial in ameliorating the rising worries about mitochondria biogenesis and triggering mitophagy to remove depleted mitochondria, therefore reducing disease pathogenesis.

Effect of syringic acid on steroid and gonadotropic hormones, hematological indices, sperm characteristics and morphologies, and markers of tissue damage in methyl cellosolve-administered rats.

Methyl cellosolve (MTC) is an established gonadotoxic and hematotoxic compound that is commonly and universally utilized in herbicide, liquid soap, stain, dye, paint, and brake fluid manufacturing industries as a solvent. Due to its wide range usage, this study therefore investigated the effect of syringic acid (SYAC) on hematological indices, sperm characteristics and morphologies, and markers of tissue damage in MTC administered male Wistar rats. Thirty (30) rats divided into six groups were used. Rats in group 1 served as control, those in group 2 were administered MTC for 30 consecutive days, those in groups 3, 4, and 5 were treated with 25, 50, and 75 mg/kg body weight of SYAC respectively also for 30 consecutive days immediately after each day MTC administrations, while rats in group 6 received 75 mg/kg body weight of SYAC only throughout. Compared with control, administrations of MTC resulted in a significant decrease in spermatozoa count, number of normal and live spermatozoa, Hb count, MCH, MCHC, serum TC, and LH, while number of abnormal spermatozoa, RBC and WBC counts, activities of serum AST, ALT, GGT, LDH, and ADH were significantly increased. Treatments with 25 mg/kg of SYAC significantly reduced the RBC and WBC counts, serum activities of AST, ALT, GGT, and increased TC concentration. Treatments with 50 mg/kg SYAC significantly lowered the number of abnormal spermatozoa, RBC count, activities of serum ALT, AST, LDH, ADH, and increased the number of normal spermatozoa, MCV, MCH, and MCHC, while 75 mg/kg of SYAC significantly decreased the serum activities of AST, ALT, GGT, LDH, ADH, and increased serum TC concentration. Findings from this study have revealed the hepatoprotective effect of SYAC at all doses investigated but did not confer spermatoprotection and hematoprotection against MTC-induced toxicities, and looking at the 3 doses investigated, 50 mg/kg of SYAC yielded the best effect.

Effect of Flavonoid-Rich Extract From Dalbergiella welwitschii Leaf on Redox, Cholinergic, Monoaminergic, and Purinergic Dysfunction in Oxidative Testicular Injury: Ex Vivo and In Silico Studies.

The antioxidant, cholinergic, monoaminergic, and purinergic activities of flavonoid-rich extract from Dalbergiella welwitschii leaf (FEDW) were investigated on oxidative testicular injury (ex vivo) due to the local report on the use of this plant as anti-testicular injury. Flavonoid extract was obtained from FEDW using a standard procedure. Five male albino rats were used, testes harvested and incubated with FeSO4 for accessing the cholinergic, monoaminergic, and purinergic activities of the FEDW (ex vivo). Testicular tissues incubated with FeSO4 demonstrated a significant decrease in antioxidant biomarkers, arginase, ATPase, ENTPDase, 5'-nucleotidase, and PDE-5 activities, as well as Zn and sialic acid levels with an upsurge in malondialdehyde (MDA), and NO levels, myeloperoxidase, cholinesterases, monoamine oxidase (MAO), and angiotensin-converting enzyme (ACE) activities. Treatment of testicular tissues incubated with FeSO4 via different concentrations of FEDW significantly increased the activities of antioxidant, arginase, ATPase, E-NTPDase, 5'-nucleotidase, phosphodiesterase-5 (PDE-5), as well as Zn and sialic acid levels with a significant decrease in MDA, nitric oxide (NO), myeloperoxidase, cholinesterases, MAO, and ACE levels. Molecular docking revealed the molecular interactions of cyclooxygenase-2 (COX-2) with ellagic acid, piperine, and caffeine with piperine and caffeine obeyed the druggability and pharmacokinetic. These findings point to FEDW as a possible potential for the treatment of oxidative testicular injury.

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.

Recombinant Expression and Biophysical Characterization of a Druggable Schistosoma mansoni Universal Stress G4LZI3 Protein.

Purpose: Universal stress protein (USP) from Schistosoma mansoni, designated as G4LZI3, waspreviously hypothesised as a druggable target and vaccine candidate for human schistosomiasis.The purpose of this study is to characterize a purified recombinant G4LZI3 preliminarily forsubsequent structural characterization, which will provide baseline structural data for futurefunctional studies for the discovery, design and development of new schistosomal drugs for thetreatment, control and elimination of schistosomiasis. Methods: Restriction digest analysis of a GenScript-synthesised codon-optimised G4LZI3gene construct was carried out to ascertain its integrity and size. Thereafter, the pQE30-G4LZI3 construct was transformed into an M15 bacterial expression host. Transformed cellswere induced with isopropyl ß-D-thiogalactoside for recombinant protein expression of anappreciable amount of pQE30-G4LZI3, which was subsequently purified with fast proteinliquid chromatography (FPLC) and a size exclusion chromatographic purification scheme.Preliminary biophysical characterization of the 6X His-tagged G4LZI3 was done to determineits secondary structure characteristics and protein stability. Results: A molecular weight protein of 20.3 kDa was confirmed subsequent to restriction digestanalysis, while heterologous protein expression yielded a highly soluble and considerableamount of histidine-tagged G4LZI3 protein, which was successfully purified to homogeneity.Biophysical characterization indicated that the protein was well folded, heat-stable, had thefunctional groups and secondary structure composition required and was thus amenable tofurther structural characterization and determination. Conclusion: Biophysical characterization of purified G4LZI3 showed that further structuralstudies can be embarked upon on the use of G4LZI3 as a druggable target and possibly avaccine target against schistosomiasis via vaccinomics.

Aqueous extract of Solanum macrocapon Linn leaf abate diabetic cardiomyopathy by attenuating oxidative stress and inflammation in rats.

In this research, the beneficial roles of aqueous leaf extract of Solanum macrocarpon (SM) on diabetic cardiomyopathy were evaluated. Diabetic rats (induced with alloxan) were given varying doses of SM aqueous leaves extract for 28 days, and the animals were sacrificed. A series of diabetic cardiomyopathy parameters were determined. Diabetic rats showed hyperglycemia, hyperlipidemia, with a momentous upsurge in lactate dehydrogenase, creatine kinase, cardiac troponin I activities as well as inflammatory markers. Also, diabetic rats demonstrated a substantial decline in the activities of antioxidant enzymes in relation to other groups. Administration of different doses of SM aqueous leaf extract to diabetic rats demonstrated normoglycemia, normolipidemia, reduced the activities of lactate dehydrogenase, creatine kinase, cardiac troponin I, and inflammatory levels as well as an increase in the antioxidant enzyme activities. In conclusion, the results suggest that SM aqueous leaf extract ameliorates diabetic cardiomyopathy. PRACTICAL APPLICATIONS: This study examined the role of Solanum macrocarpon (SM) aqueous leaf extract in diabetic cardiomyopathy. Results revealed that SM might be useful in ameliorating diabetic cardiomyopathy.