Search

Amos Sunday Onikanni,1– 3,* Bashir Lawal,4,5,* Augustine O Olusola,1 Janet O Olugbodi,6 Saidu Sani,7 Basiru Olaitan Ajiboye,8 Omotayo B Ilesanmi,9 Mohammed Alqarni,10 Gomaa Mostafa-Hedeab,11,12 Ahmad J Obaidullah,13,14 Gaber El-Saber Batiha,15 Alexander TH Wu16– 21 1Toxicology and Environmental Laboratory, Department of Biochemistry, Faculty of Science, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria; 2Biochemistry Unit, Department of Chemical Sciences, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria; 3Graduate Institute of Biomedical Science, College of Medicine, China Medical University, Taipei, Taiwan; 4PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, 11031, Taiwan; 5Graduate Institute of Cancer Biology & Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; 6Department of Biochemistry, Bingham University, Karu, Nigeria; 7Department of Biochemistry, Faculty of Biological Science, Alex Ekwueme Federal University Ndufu Alike IkwoD, Abakaliki, Ebonyi State, Nigeria; 8Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Faculty of Science, Federal University, Oye-Ekiti, Ekiti State, Nigeria; 9Department of Biochemistry, Faculty of Science, Federal University Otuoke, Ogbia, Bayelsa State, 23401, Nigeria; 10Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia; 11Pharmacology Department & Health Research Unit, Medical College, Jouf University, Sakakah, Saudi Arabia; 12Pharmacology Department, Faculty of Medicine, Beni-Suef University, Beni Suef, Egypt; 13Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia; 14Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia; 15Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt; 16The PhD Program of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; 17International Ph.D. Program for Translational Science, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; 18TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, 11031, Taiwan; 19Clinical Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, 11031, Taiwan; 20Taipei Heart Institute, Taipei Medical University, Taipei, 11031, Taiwan; 21Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, 11490, Taiwan*These authors contributed equally to this workCorrespondence: Alexander TH Wu Tel +886 2 2697 2035Email chaw1211@tmu.edu.twBackground: Sterculia tragacantha is a medicinal plant commonly used in the western part of Nigeria, for managing diabetes mellitus. However, there is a dearth of scientific information on the antidiabetic and neuroprotective properties of the plant.Methods: The in silico, in vitro and in vivo models were used to evaluate the antioxidants, antidiabetic, anti-inflammatory and neuroprotective potential of aqueous extract of Sterculia tragacantha leaf (AESTL) in streptozotocin (STZ)-induced diabetic rats. Thirty (30) male albino rats (155.34± 6.33 g) were intraperitoneal injected with 40 mg/kg of freshly prepared streptozotocin and were divided into 5 groups (A-E) of 6 animals each. Groups A–D were treated with 0, 150 and 300 mg/kg of AESTL, and 200 mg/kg body weight of metformin respectively, while group E serve as the normal control.Results: The results of in vitro analysis revealed dose-dependent antioxidant activities; ABTS (IC50 = 63.03± 2.57 μg/mL), DPPH (117.49± 2.35 μg/mL), FRAP (15.19± 0.98 mmol/100g), TAC (43.38± 0.96 mg/100g), hypoglycaemic effect; α-amylase (IC50 = 77.21± 4.35 μg/mL) and α-glucosidase (IC50 = 443.25± 12.35), and anti-cholinesterase; AChE (IC50 = 113.07± 3.42 μg/mL) and BChE (IC50 = 87.50± 4.32 μg/mL) activities of AESTL. In vivo study revealed dose-dependent hypoglycemic effect and body weight improvement in rats treated with the AESTL. In addition, AESTL improved the antioxidant status and attenuated STZ-induced dysregulations of Na+-K+-ATPase, cholinesterases and neurotransmitters in the brain tissue of experimental rats. The results also demonstrated that AESTL could regulate anti-inflammatory response via inhibition of COX-2/NO signaling axis in the brain of diabetic rats. Molecular docking analysis revealed that epicatechin and procyanidin B2, the bioactive compounds from AESTL, docked well to the binding cavities of acetylcholinesterase, butyrylcholinesterase, α-amylase and α-glucosidase with binding affinities ranges between – 8.0 and – 11.4 kcal/mol, suggesting that these compounds are the bioactive component that could be responsible for the antidiabetic and neuroprotective activities of AESTL.Conclusion: The results of the present study strongly suggested that the AESTL extract could be very useful for halting diabetes progression and its associated neuroinflammation complications.Keywords: Sterculia tragacantha, cholinesterase, antidiabetic, neurotransmitters, oxidative stress markers

This study investigated the effects of flavonoid-rich extract from Hibiscus sabdariffa L. (Malvaceae) leaves on liver damage in streptozotocin-induced diabetic rats by evaluating various biochemical parameters, including the molecular gene expressions of Nrf-2 and HO-1 as well as histological parameters. The extract was found to significantly reduce liver damage, as evidenced by lower levels of fragmented DNA and protein carbonyl concentrations. Oxidative stress markers, including malondialdehyde (MDA) level, were also significantly ( p  < 0.05) decreased, while antioxidant biomarkers, like reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) were enhanced. Additionally, the extract improved the activities of key liver enzymes, including phosphatases and transaminases, and increased albumin levels. Importantly, the study demonstrated that H. sabdariffa extract effectively regulated the expression of Nrf-2 and HO-1, suggesting a significant role in mitigating liver damage. These findings highlight its potential as a therapeutic agent for liver protection in diabetic conditions., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Erectile dysfunction (ED) is a multifactorial social problem affecting men worldwide. While phosphodiesterase type 5 inhibitors (PDE5) like sildenafil are commonly used, they often present side effects, underscoring the need for alternative therapies. Therefore, this study investigated the potential of phytochemicals from Detarium senegalense in the management of ED. A library of phytochemicals from Detarium senegalense was generated, prepared, and interacted with six key enzymes implicated in ED, including PDE5, using the Schrödinger Maestro suite. The results identified catechin, epicatechin, and gallic acid as the leading compounds with significant binding affinities for the targeted enzymes. Catechin and epicatechin (-9.877 and -11.408 kcal/mol, respectively) exhibited comparable binding affinities to sildenafil (-11.926 kcal/mol) on PDE5. The MD simulation results also revealed superior stability and ability to maintain interaction with key amino acids at the active site of PDE5 over the entire simulation period for these compounds. These compounds also demonstrated favorable ADMET profiles over sildenafil, including high gastrointestinal absorption and no violation of Lipinski's rule, indicating good bioavailability and drug likeness. These findings suggest that flavonoids from Detarium senegalense , especially catechin and epicatechin, have potential in the management of ED by interacting with multiple targets involved in its pathogenesis.

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Studies suggest that medicinal plant extracts can help reduce the neuron degeneration associated with diabetes. In this study, the neuroprotective effect of the alkaloid-rich extract from the leaves of Lannea egregia was assessed in rats with diabetes induced by streptozotocin (STZ)., Methods: Lannea egregia alkaloid-rich analysis was carried out via a known procedure. The rats were randomly assigned into five treatment groups (n = 8): normal control, diabetic-induced rats (45 mg/kg STZ), and diabetic rats treated with low doses of Lannea egregia leaf alkaloid-rich extract (50 mg/kg b.w, LEL) and high (100 mg/kg b.w, LEH) (300 mg/kg and 150 mg/kg), and metformin (200 mg/kg). On 22nd day of the experiment, animals were sacrificed, and their blood and brains were collected for neuro-biomarker analysis., Results: Diabetic-induced rats that received metformin, LEL and LEH exhibited considerably reduced levels of dopamine, serotonin, norepinephrine, NO, MDA, and AChE, BChE activities when compared to untreated diabetic animals. Additionally, rats with diabetes that received treatment with metformin, LEL and LEH displayed a noticeable increase in ENTPDase, Na/K ATPase, GST, CAT, GPx, and SOD activities when compared to the untreated diabetic rats. Histological examination revealed improved brain architecture in the treated groups in contrast to those in diabetic-induced rats., Conclusion: The alkaloid-rich extracts of Lannea egregia might be effective in normalizing brain damage caused by complications of diabetes mellitus., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that they no known financial interests that could have appeared to influence the work reported in this paper, (© 2024 The Authors.)

Photodynamic therapy (PDT) is a groundbreaking approach involving the induction of cytotoxic reactive oxygen species (ROS) within tumors through visible light activation of photosensitizers (PS) in the presence of molecular oxygen. This innovative therapy has demonstrated success in treating various cancers. While PDT proves highly effective in most solid tumors, there are indications that certain cancers exhibit resistance, and some initially responsive cancers may develop intrinsic or acquired resistance to PDT. The molecular mechanisms underlying this resistance are not fully understood. Recent evidence suggests that, akin to other traditional cancer treatments, the activation of survival pathways, such as the KEAP1/Nrf2 signaling pathway, is emerging as an important mechanism of post-PDT resistance in many cancers. This article explores the dual role of Nrf2, highlighting evidence linking aberrant Nrf2 expression to treatment resistance across a range of cancers. Additionally, it delves into the specific role of Nrf2 in the context of photodynamic therapy for cancers, emphasizing evidence that suggests Nrf2-mediated upregulation of antioxidant responses and induction of drug efflux transporters are potential mechanisms of resistance to PDT in diverse cancer types. Therefore, understanding the specific role(s) of Nrf2 in PDT resistance may pave the way for the development of more effective cancer treatments using PDT., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Ajuwon et al.)

Objectives: This study investigated the antidiabetic effects of the methanolic extract of E. africanum (MEEA) stem bark on streptozotocin (STZ)-induced diabetic nephropathy (DN) in Wistar rats., Methods: The in vitro enzyme (α-amylase) inhibitory activity of MEEA was measured using a standard procedure. Diabetic rats with fasting blood glucose above 250 mg/dL were considered diabetic and were divided into the following groups: control (distilled water-treated), diabetic-control, diabetic metformin (100 mg/kg), diabetes + MEEA (150 mg/kg), and diabetes + MEEA (300 mg/kg) via oral gavage once daily for 14 days. At the end of the experimental period, kidney tissues were collected for biochemical and histological analyses. Kidney apoptosis and marker gene expression were measured by real-time quantitative PCR., Results: MEEA exhibited α-amylase inhibitory effects. MEEA significantly (p<0.05) reduced the STZ-induced increases in blood glucose, serum urea, serum creatinine, uric acid, alanine aminotransferase, alkaline phosphatase, and malondialdehyde and increased the STZ-induced decreases in superoxide dismutase, catalase, and reduced glutathione. In addition, MEEA protects against DN by significantly downregulating the mRNA expression of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response binding protein (CREB), and cFOS and upregulating B-cell lymphoma 2 (Bcl-2), suggesting that the nephroprotective ability of MEEA is due to the modulation of the cAMP/PKA/CREB/cFOS signaling pathway. Furthermore, MEEA treatment protected against histopathological alterations observed in diabetic rats., Conclusions: The data from this study suggest that MEEA modulates glucose homeostasis and inhibits redox imbalance in DN rats., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

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 ΔG bind (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., (© 2024. The Author(s).)

Background: Spilanthes filicaulis (Schumach. & Thonn.) C. D Adam is a shrubby plant of the Asteraceae family that has medicinal benefits for the pharmaceutical and cosmetic industries., Purpose: The purpose of this study was to assess the effectiveness of Spilanthes filicaulis leaf extract in a streptozotocin (STZ)-induced rat model and the associated signaling pathways., Methods: A sample of 25 male Wistar rats was randomly assigned to groups I, II, III, IV, and V. Each group included five animals, i.e., control rats, diabetic control rats, diabetic rats treated with metformin, and diabetic rats treated with 150 mg/kg/bw and 300 mg/kg/bw of the methanolic extract of S. filicaulis leaves (MESFL). Treatment was administered for 15 successive days via oral gavage. After 15 days, the rats were evaluated for fasting blood glucose (FBG), glycated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (MDA), hexokinase, and glucose-6-phosphatase activities. Gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPAR-γ), kelch-like ECH-associated protein 1 (Keap1), protein tyrosine phosphatase 1B (PTP1B) and the antiapoptotic protein caspase-3 were examined., Results: MESFL was administered to diabetic rats, and changes in body weight, fasting blood glucose (FBG) and HbA1c were restored. Furthermore, in diabetic rats, S. filicaulis significantly reduced the levels of triglycerides (TGs), total cholesterol (TC), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) and significantly increased HDL. S. filicaulis improved ALT, AST, and ALP enzyme activity in diabetic rats. MDA levels decreased considerably with increasing activity of antioxidant enzymes, such as GST, SOD, CAT and GSH, in diabetic liver rats treated with S. filicaulis. Diabetic rats treated with MESFL and metformin exhibited upregulated mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Kelch-like ECH-associated protein 1 (Keap1) and protein tyrosine phosphatase 1B (PTP1B) mRNA expression in the liver was downregulated in diabetic rats treated with MESFL and metformin. In addition, MESFL downregulated the mRNA expression of caspase-3 in diabetic rats., Conclusion: It can be concluded from the data presented in this study that MESFL exerts a protective effect on diabetic rats due to its antidiabetic, antioxidant, antihyperlipidemic and antiapoptotic effects and may be considered a treatment for T2DM., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ojo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

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.

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.

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-1β), 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., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

High dose of fluoride intake is associated with toxic effects on kidney and cardiac tissues. This study evaluated the potential protective effect of fermented rooibos tea (RTE) on sodium fluoride (NaF)-induced cardiorenal toxicity in rats. Male Wistar rats (n = 56) were randomly allocated into one of seven equal groups: control, NaF (100 mg/kg orally), NaF + RTE (2%, w/v), NaF + RTE (4%, w/v), NaF + lisinopril (10 mg/kg orally), 2% RTE, and 4% RTE. The experiment lasted for 14 days and RTE was administered to the rats as their sole source of drinking fluid. NaF induced cardiorenal toxicity indicated by elevated level of urea, creatinine, LDH, creatinine kinase-MB, and cardiac troponin I in the serum, accompanied by altered histopathology of the kidney and heart. Furthermore, levels of H 2 O 2 , malondialdehyde, and NO were elevated, while GSH level was depleted in the kidney and heart due to NaF intoxication. Protein levels of c-reactive protein, TNFα, IL-1B, and NF-κB were increased by NaF in the serum, kidney, and heart. RTE at 2% and 4% (w/v) reversed cardiorenal toxicity, resolved histopathological impairment, attenuated oxidative stress and inhibited formation of pro-inflammatory markers. RTE at both concentrations down-regulates the mRNA expression of NF-κB, and upregulates the mRNA expression of both IκB and IκKB, thus blocking the activation of NF-κB signaling pathway. Taken together, these results clearly suggest that the protective potential of rooibos tea against NaF-induced cardiorenal toxicity, oxidative stress, and inflammation may be associated with the modulation of the NF-κB signaling pathway., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Long-term antiretroviral drug toxicity may exacerbate the impact of HAART-Cyperus esculentus (C. esculentus) interactions on testicular function in HIV-infected individuals. This study examined the ability of C. esculentus plants to treat testicular dysfunction, which is thought to be a probable side effect of antiretroviral toxicity. Adult Wistar male rats weighing 90-110 g were divided into six groups and administered the prescribed treatments. In addition to testicular histology and stereological parameters, testosterone levels, follicle-stimulating hormone levels, antioxidant markers, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione levels were also evaluated. The adverse consequences of highly active antiretroviral therapy (HAART) include considerable loss of germ cells, enlargement of the tubular lumen, widening of interstitial gaps, and severe hypocellularity. Compared to the other treatment groups, MDA levels dramatically increased, whereas GSH and antioxidant enzyme (SOD) levels significantly decreased. Testicular architecture was largely conserved after treatment with C. esculentus, with a notable increase in the cellular densities of germinal and interstitial cells and a notable decrease in the tubular lumen. Vacuolation, architectural malformations, and hypoplastic changes were reduced. Significant improvements were also observed in C. esculentus in terms of elevated antioxidant SOD and GSH levels and decreased MDA levels. C. esculentus reduced architectural distortions and testicular dysfunction caused by HAART, and improved testicular morphology. Further exploration of these pathways is required.

Populus ciliata (PCCR) is traditionally used to treat muscular swelling, inflammation, pain, and fever. The current study was designed to validate the potential of aqueous ethanolic extract of the plant against inflammation, peripheral neuropathy, and pain in arthritic rats. The PCCR was chemically characterized by gas chromatography-mass spectroscopy and high-performance liquid chromatography. In vitro antioxidant, and in vitro anti-inflammatory assays were carried out on PCCR. For anti-arthritic potential, Wistar rats' rear paws were injected with 0.1 ml Complete Freund's Adjuvant using methotrexate (3 mg/kg/week) as standard control. PCCR at 100, 200, and 400 mg/kg was given orally to arthritic rats for 21 days. The PCCR exhibited significant inhibition of bovine serum albumin denaturation (IC-50: 202.1 µg/ml), egg albumin denaturation (IC-50:553.5 mg/ml) and RBC membrane stabilization (IC-50: 122.5 µg/ml) and antioxidant (IC-50 = 49.43 µg/ml) activities. The PCCR notably decreased the paw diameter and increased body weight of treated arthritic animals as equated to diseased control. The treatment notably (p < 0.05-0.0001) decreased malondialdehyde, and increased superoxide dismutase, reduced glutathione, and catalase in the liver and sciatic nerve homogenate in compared to diseased rats. The PCCR treatment remarkably (p < 0.05-0.0001) regulated the levels of nor-adrenaline and serotonin in sciatic nerve in contrast to diseased rats. Treatment with PCCR improved the motor activity, pain, ligament degeneration, and synovial hyperplasia in arthritic rats. Moreover, PCCR significantly (p < 0.01-0.0001) decreased the IL-6 and TNF-α. It is evident from the current study that PCCR had ameliorated polyarthritis and peripheral neuropathy through reduction of inflammatory markers, and improvement of oxidative stress might be due to presence of phenolic acids, flavonoids, phytosterols, and other fatty acids., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This experiment was conducted to evaluate the Dalbergiella welwitschia alkaloid-rich extracts on liver damage in streptozotocin-induced diabetic rats. Hence, to induce diabetes, 45 mg/kg body weight of streptozotocin was intraperitoneally injected into the Wistar rats. Subsequently, 5 % (w/v) of glucose water was given to the induced animals for 24 h. Thus, the animals (48) were grouped into five groups (n = 8), containing normal control (NC), diabetic control (DC), diabetic rats placed on low (50 mg/kg body weight) and high (100 mg/kg body weight) doses of D. welwitschi alkaloid-rich leaf extracts (i.e. DWL and DWH respectively), and diabetic rats administered 200 mg/kg body weight of metformin (MET). The animals were sacrificed on the 21st day of the experiment, blood and liver were harvested, and different liver damage biomarkers were evaluated. The results obtained demonstrated that diabetic rats administered DWL, DWH and MET significantly (p < 0.05) increased hepatic AST, ALT, albumin, SOD, CAT, GSH, and GPX levels when compared to DC with no significant (p > 0.05) different when compared with NC. Also, diabetic rats administered DWL, DWH and MET revealed a significant (p < 0.05) decrease in GGT and MDA levels, as well as, fragmented DNA and protein carbonyl levels when compared to DC with no significant (p > 0.05) different when compared with NC. In addition, histological examination revealed that diabetic rats placed on DWL, DWH and MET normalized the hepatocytes. Consequently, it can be inferred that alkaloid-rich extracts from D. welwitschi leaf could be helpful in improving liver damage associated with diabetes mellitus rats., Competing Interests: Declaration of Competing Interest We hope if published it will be helpful for type II diabetes mellitus worldwide. This manuscript is solely submitted to this your reputable journal. All authors have contributed significantly to this manuscript and agreed on the content of the manuscript. In addition, the authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: (s): Metabolic syndrome is a collection of metabolic abnormalities that includes hyperglycemia, dyslipidemia, hypertension, and obesity. Ellagic acid is found in various fruits and vegetables. It has been reported to have several pharmacological properties, such as antibacterial, antifungal, antiviral, anti-inflammatory, hepatoprotective, cardioprotective, chemopreventive, neuroprotective, gastroprotective, and antidiabetic. Our current study aims to shed light on the probable efficiency of ellagic acid in managing metabolic syndrome and its complications., Materials and Methods: To prepare the present review, the databases or search engines utilized included Scopus, PubMed, Science Direct, and Google Scholar, and relevant articles have been gathered with no time limit until March 2023., Results: Several investigations indicated that ellagic acid could be a potent compound for the treatment of many disorders such as diabetes, hypertension, and hyperlipidemia by various mechanisms, including increasing insulin secretion, insulin receptor substrate protein 1 expression, regulating glucose transporter 4, triglyceride, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), attenuating tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), reactive oxygen species (ROS), malondialdehyde (MDA), and oxidative stress in related tissues. Furthermore, ellagic acid ameliorates mitochondrial function, upregulates uncoupling protein 1 (found in brown and white adipose tissues), and regulates blood levels of nitrate/nitrite and vascular relaxations in response to acetylcholine and sodium nitroprusside., Conclusion: Ellagic acid can treat or manage metabolic syndrome and associated complications, according to earlier studies. To validate the beneficial effects of ellagic acid on metabolic syndrome, additional preclinical and clinical research is necessary., Competing Interests: 3.1The authors declare no competing interests.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Zingerone is a flavor phytochemical present in ginger, a flowering plant belonging to the Zingiberaceae family used as a condiment and herbal remedy. It possesses anti-inflammatory, antioxidant, and anti-apoptotic properties and also exhibits protective effects against radiation, chemicals, biological toxins, and oxidative stress. The current comprehensive literature review was performed in order to assess the therapeutical and protective properties of zingerone against various chemical and natural toxins by considering the mechanisms of action. Extensive searches were performed on Scopus, Web of Science, PubMed, and Google Scholar databases. Zingerone lessens oxidative stress, inflammation, apoptosis, and oxidative DNA damage by increasing the activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPX). It prevents alginate production, which increases the cell's susceptibility to macrophages, serum, and antibiotics and dramatically lowers the generation of proinflammatory cytokines brought on by lipopolysaccharide (LPS). Cytokine production, MAPK, and NF-κB activation are all inhibited dose-dependently by zingerone. Zingerone also reduces 8-OHdG over-expression in the liver tissue and the expression of NADPH oxidase 4 (NOX4), inflammatory cytokines (e.g., IFN-γ, IL-17, IL-6, COX-2, TNF-α, and iNOS mRNA level), decreases macrophage inflammatory protein cytokines and eliminates free radicals. It also suppresses matrix metalloproteinase-2 (MMP-2) and MMP-9 during tumor progression, showing its anti-angiogenic activity. Strong radioprotective properties of zingerone are demonstrated against radiation-induced toxicity. The authors hope this review gives researchers some insight into conducting novel clinical and preclinical studies on pharmaceutical applications and the efficiency of zingerone in cancer treatment, and drug adverse effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Mangiferin (MGF), a xanthone derived from Mangifera indica L., initially employed as a nutraceutical, is now being explored extensively for its anticancer potential. Scientists across the globe have explored this bioactive for managing a variety of cancers using validated in vitro and in vivo models. The in vitro anticancer potential of this biomolecule on well-established breast cancer cell lines such as MDA-MB-23, BEAS-2B cells and MCF-7 is closer to many approved synthetic anticancer agents. However, the solubility and bioavailability of this xanthone are the main challenges, and its oral bioavailability is reported to be less than 2%, and its aqueous solubility is also 0.111 mg/mL. Nano-drug delivery systems have attempted to deliver the drugs at the desired site at a desired rate in desired amounts. Many researchers have explored various nanotechnology-based approaches to provide effective and safe delivery of mangiferin for cancer therapy. Nanoparticles were used as carriers to encapsulate mangiferin, protecting it from degradation and facilitating its delivery to cancer cells. They have attempted to enhance the bioavailability, safety and efficacy of this very bioactive using drug delivery approaches. The present review focuses on the origin and structure elucidation of mangiferin and its derivatives and the benefits of this bioactive. The review also offers insight into the delivery-related challenges of mangiferin and its applications in nanosized forms against cancer. The use of a relatively new deep-learning approach to solve the pharmacokinetic issues of this bioactive has also been discussed. The review also critically analyzes the future hope for mangiferin as a therapeutic agent for cancer management.

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 (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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction Diabetes mellitus is still a raging disease not fully subdued globally, especially in Africa. Our study aims to evaluate the anti-diabetic potentials of Justicia carnea extracts [crude (JCC), free (JFP) and bound phenol (JBP) fractions], in streptozotocin (STZ)-induced type-1 diabetes in male albino rats. Materials and Methods About thirty (30) animals were induced for type 1 diabetes with STZ; thereafter, treatment began for 14 days, after which the animals were euthanized, blood/serum was collected, the liver was removed and divided into two portions, for biochemical and histopathological analyses. Standard procedures were used to evaluate the liver biomarkers, like alanine transaminase (ALT), fructose-1,6-bisphosphatase, glucose-6- phosphatase, hexokinase activities, albumin, bilirubin, hepatic glucose concentrations; antioxidant status and pro- and anti-inflammatory cytokines were similarly assessed. Results These results revealed that the extracts ameliorated the harmful effects of STZ-induced diabetes in the liver by enhancing the activities of liver-based biomarkers, reducing the concentrations of pro-inflammatory cytokines and increasing the anti-inflammatory cytokine. Discussion The results agreed with previous research, and the free phenol fraction showed excellent results compared to others Conclusion These suggested that J. carnea could serve as an alternative remedy in ameliorating liver complications linked to oxidative damage and inflammation in STZ-induced type-1 diabetes.

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.

Cadmium is a highly neurotoxic heavy metal that disrupts membranes and causes oxidative stress in the brain. The study aimed to investigate the neuroprotective effect of gallic acid on oxidative damage in the brains of Wistar rats exposed to cadmium chloride (CdCl 2 ). Male Wistar rats were divided into four groups of five rats each. Group 1 was administered distilled water only throughout the study. Throughout the study, Group 2 received CdCl 2 alone (5 mg/kg b.w./day), Group 3 received gallic acid (20 mg/kg b.w./day), and Group 4 received CdCl 2  + gallic acid (20 mg/kg). Treatments were oral with distilled water as a vehicle. The study lasted 21 days. In the brain, the activities of cholinesterase and antioxidant enzymes were evaluated, as well as the levels of reduced glutathione, malondialdehyde, neurotransmitters, Na+/K+ ATPase, myeloperoxidase activity, nitric oxide, and interleukin-6. CdCl 2 -induced brain impairments in experimental animals and gallic acid prevents the following CdCl 2 -induced activities: inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), elevated neurotransmitters (serotonin and dopamine), decreased antioxidant enzymes (superoxide dismutase, catalase), decreased glutathione, Na+/K+ ATPases, and increased MDA and neuroinflammatory markers (myeloperoxidase (MPO), nitric oxide, and interleukin-6 in the brain of experimental rats exposed to CdCl 2 (p < 0.05). Taken together, the neuroprotective effects of gallic acid on CdCl 2 -induced toxicity in the brains of rats suggest its potent antioxidant and neurotherapeutic properties., (© 2023. The Author(s).)

Mitochondria malfunction is linked to the development of β-cell failure and a variety of neurodegenerative disorders. Pancreatic β-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 Ca 2+ 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 β-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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The contribution of prefrontal-hippocampal interactions to brain function of people infected with HIV may be aggravated by toxicities due to long-term use of antiretroviral agents. This study was designed to investigate the curative potential of Epigallotatechin gallate (EGCG) in the treatment of neurodegenerative disorders as a possible consequence of antiretroviral toxicity. Twenty-four adult male Wistar rats, weighing 80~100g, were divided into four groups and treated as follows: control A (distilled water), B (HAART), C (EGCG 2.5mg/kg), D (EGCG 2.5mg/kg) + HAART) Brain histology, immunohistochemistry, and oxidative stress markers such as superoxide dismutase (SOD), glutathione (GSH),catalase (CAT)  and malondialdehyde (MDA) were examined. The use of highly active antiretroviral therapy (HAART) showed extensive architectural deformation with pyknotic neuronal cells and obliterated neurons in the hippocampus and prefrontal cortex. Expression of inflammasome cells was also evident in this group. MDA levels increased significantly with a significant reduction in the levels of GSH, as well as antioxidant enzyme (SOD and CAT) activities compared to other treatment groups. Treatment with EGCG resulted in partial neuronal restoration of histopathological alterations, and modulation of NLRP3 inflammasome in the hippocampus and prefrontal cortex. EGCG also showed significant improvements in terms of increased antioxidant levels of SOD, GSH, CAT and a reduced MDA level and well-preserved brain architecture. Epigallocatechin gallate improves brain morphology and function with a reversal of HAART-induced alterations.

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

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., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

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 FeSO 4 for accessing the cholinergic, monoaminergic, and purinergic activities of the FEDW (ex vivo). Testicular tissues incubated with FeSO 4 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 FeSO 4 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., Competing Interests: Declaration Of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

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., (© 2022 Wiley Periodicals LLC.)

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 A 3 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 A 3 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.

The treatment of diabetes involves the use of herbal plants, attracting interest in their cost-effectiveness and efficacy. An aqueous extract of Persea americana seeds (AEPAS) was explored in this study as a possible therapeutic agent in rats with diabetes mellitus. The induction of diabetes in the rats was achieved by injecting 65 mg/kg body weight (BWt) of alloxan along with 5% glucose. This study was conducted using thirty-six (36) male Wistar rats. The animals were divided into 6 equal groups, (n = 6) and treated for 14 days. In vitro assays for total flavonoid, phenols, FRAP, DPPH, NO, α-amylase, and α-glucosidase, were performed. Biochemical indices fasting blood sugar (FBS), BWt, serum insulin, liver hexokinase, G6P, FBP, liver glycogen, IL-6, TNF-α, and NF-ĸB in the serum, were investigated as well as the mRNA expressions of PCNA, Bcl2, PI3K/Akt in the liver and pancreas. The in vitro analyses showed the potency of AEPAS against free radicals and its enzyme inhibitory potential as compared with the positive controls. AEPAS showed a marked decrease in alloxan-induced increases in FBG, TG, LDL-c, G6P, F-1, 6-BP, MDA, IL-6, TNF-α, and NF-ĸB and increased alloxan-induced decreases in liver glycogen, hexokinase, and HDL-c. The diabetic control group exhibited pancreatic dysfunction as evidenced by a reduction in serum insulin, HOMA-β, expressions of PI3K/AKT, Bcl-2, and PCNA combined with an elevation in HOMA-IR. The HPLC revealed luteolin and myricetin to be the phytochemicals that were present in the highest concentration in AEPAS. The outcome of this research showed that the administration of AEPAS can promote the activation of the PI3K/AkT pathway and the inhibition of β-cell death, which may be the primary mechanism by which AEPAS promotes insulin sensitivity and regulates glycolipid metabolism., (© 2022. The Author(s).)

The worldwide expanding increment in cancer pervasiveness is disturbing and this disease ranks among the main causes of mortality in both developing and developed countries. Unfortunately, available treatment options come with serious side effects and do not guarantee complete success. Although numerous models have been proposed for the development of better therapeutic agent, however the exact mechanism are still poorly understood. This then calls for continued research aimed at developing new drugs as an alternative or adjuvant anticancer agents. Here we have identified five vital proteins (CDK-2, Bcl-2, CDK-6, VEGFR, and IGF-1R) that aid tumor growth and we inhibited the activity of these proteins with Puerarin. Puerarin is an isoflavonoid C-glycosides used as a therapeutic agent against various human ailments. Our findings revealed that Puerarin fulfilled Veber's rule. Added to this, CDK-6 and Bcl-2 had better glide scores for puerarin than the control (doxorubicin) and molecular simulation showed the stability of the complexes. These findings suggest that inhibiting CDK-6 and Bcl-2 with Puerarin could prove more effective in the management of cancer than doxorubicin. Overall, this study provides a new direction that could facilitate rational drug design for cancer.Communicated by Ramaswamy H. Sarma.

A high increase witnessed in type II diabetes mellitus (T2DM) globally has increasingly posed a serious threat to global increases in liver cancer with the association between diabetes mellitus type II and the survival rate in liver cancer patients showing unstable findings. An increase in the development and progression of chronic liver disease from diabetes mellitus patients may be connected to cancer of the liver with several links such as Hepatitis B and C virus and heavy consumption of alcohol. The link between T2DM patients and liver cancer is centered on non-alcoholic fatty liver disease (NAFLD) which could be a serious threat globally if not clinically addressed. Several reports identified metformin treatment as linked to a lower risk of liver cancer prognosis while insulin treatment or sulphonylureas posed a serious threat. Mechanistically, the biological linkage between diabetes type II mellitus and liver cancer are still complex to understand with only the existence of a relationship between NAFLD and high level of energy intake and diabetes mellitus induces hepatic damage, increased liver weight thereby causes multiple pro-inflammatory cytokines that lead to the development of liver cancer. Therefore, this review gives an account of the pathophysiological importance of liver cancer position with T2DM, with the role of NAFLD as an important factor that bridges them.

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 CdCl 2 ) 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., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: The current study evaluates the protective role of aqueous extract of Sterculia tragacantha leaf (AESTL) on pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67 and GLP-1R) and oxidative stress parameters in streptozotocin-induced diabetic rats., Methods: Diabetes mellitus was induced into the experimental Wistar animals via intraperitoneal (IP) injection of streptozotocin (35 mg/kg body weight) and 5% glucose water was given to the rats for 24 h after induction. The animals were categorized into five groups of 10 rats each as follows normal control, diabetic control, diabetic rats administered AESTL (150 and 300 mg/kg body weight) and diabetic rats administered metformin (200 mg/kg) orally for two weeks. Thereafter, the animals were euthanized, blood sample collected, pancreas harvested and some pancreatic gene expressions (such as insulin, PCNA, PDX-1, KI-67, and GLP-1R)s as well as oxidative stress parameters were analyzed., Results: The results revealed that AESTL significantly (p<0.05) reduced fasting blood glucose level, food and water intake, and lipid peroxidation in diabetic rats. Diabetic rats administered different doses of AESTL showed a substantial upsurge in body weight, antioxidant enzyme activities, and pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67, and GLP-1R)., Conclusions: It can therefore be concluded that AESTL has the ability to protect the pancreas during diabetes mellitus conditions., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: To assess the ameliorative activity of polyphenolic-rich extracts of Basella rubra leaves on β-cell dysfunction in type-II diabetes (T2DM)., Methods: Total phenolic and flavonoid contents; α-amylase and α-glucosidase inhibitory actions and qualitative analysis of the bioactive compounds of the polyphenolic-rich extract of B. rubra leaves were investigated using gas chromatography-mass spectroscopy (GC-MS). Diabetes mellitus (DM) was induced by single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and the rats were orally given bound phenolic (BPE) and free phenolic extracts (FPE) of B. rubra (B.R) leaves at 200 and 400 mg/kg b.w once daily for 14 days. Biochemical analyses were executed for evaluation of serum insulin, serum lipid profile concentrations, liver enzymes activities., Results: The extracts demonstrated antioxidant potentials and enzymes inhibitory activities in dose dependent manner; and several bioactive compounds as revealed by GC-MS. BPE and FPE considerably (p<0.05) reduced hyperglycemia, improved serum insulin levels, ameliorated the concentration of serum lipid profiles and improved liver antioxidant activities. Additionally, BPE and FPE expressively decreased alanine aminotransferases (ALT), aspartate aminotransferases (AST), gamma-glutamyl transferase (GGT) activities along with levels of bilirubin and urea when compare to diabetic control rats., Conclusions: Data acquired exhibited the ability of BPE and FPE to improve pancreatic beta-cell in streptozotocin-induced rats., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Chrysobalanus orbicularis is a medicinal plant present in West Africa in the Itsekiri speaking part of Nigeria. It is used conventionally in diabetes mellitus management. This research investigates the ameliorative activity of the aqueous leaf extract of C. orbicularis in a streptozotocin-induced diabetic rat model. Freshly prepared streptozotocin (40 mg/kg body weight [BW]) was administered intraperitoneally to induce diabetes. Three diabetic groups were placed on aqueous leaf extract of C. orbicularis at 11.076, 22.134, and 44.268 mg/kg BW respectively; a group was placed on metformin (44.28 mg/kg BW), and the other two groups were the diabetic control and normal control. The experiment lasted for 28 days, thereafter, fasting blood glucose levels and body weight variations were recorded. Also, glycogen level, antioxidant enzyme, hexokinase and glucose-6-phosphatase activities, malonaldehyde (MDA) as well as glucose transporters 2 and 4 levels were analyzed using standard procedures. Diabetic rats administered aqueous extract of C. orbicularis leaf significantly (p < 0.05) decreased the fasting blood glucose and MDA levels, and glucose-6-phosphatase activity. In addition, administration of aqueous extract of C. orbicularis leaf to diabetic rats demonstrated a momentous increase in liver glycogen level, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, glutathione transferase, and hexokinase activities as well as GLUT-2 and GLUT-4 levels. The data from this study suggest that the aqueous extract of C. orbicularis leaf may be beneficial in the management of diabetic mellitus and its secondary effects., Competing Interests: The authors declare no conflict of interest., (© 2021 Published by Elsevier Ltd.)

Purpose: In this study, antihyperglycaemic and level of gene expression of glucose transporters in alloxan-induced diabetic rats administered aqueous extract of S. macrocarpon leaves were assessed., Method and Results: Diabetes was induced by a single intraperitoneal (I.P) injection of freshly prepared alloxan. The animals were divided into six groups, euthanized on the fourteenth day of the experiment and different hyperglycaemic parameters were evaluated. Administration of different doses of the plant extract significantly (p < 0.05) reduced the fasting blood glucose level, glycated haemoglobin, serum lipid profiles, lipid peroxidation, and glucose-6-phosphatase. There was a significant (p < 0.05) increase in liver glycogen content, antioxidant enzyme activities, hexokinase activity, and expression of glucose transporter genes (GLUT-2 and GLUT-4) in diabetic rats administered different doses of S. macrocarpon., Conclusion: It can be concluded that the aqueous extract of S. macrocarpon leaves could be helpful in the management of diabetes mellitus and its metabolic complications.

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 (M pro /3CL pro ), 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 (IC 50 = 0.03 mg/L), acetone (IC 50 = 1.564 mg/L), ethyl-acetate (IC 50 = 0.382 mg/L) and methanol (IC 50 = 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., (© 2020 John Wiley & Sons Ltd.)

Sterculia tragacantha (ST) Lindl leaf is commonly used locally in the management of diabetes mellitus (DM) and its complications. This study was aimed at assessing the valuable effects of ST leaf on streptozotocin-diabetic cardiomyopathy (DCM). Streptozotocin was administered intraperitoneally to the experimental animals to induce DM, and hence, placed on different doses of ST for 14 days. Thereafter, on the 15 th day of the experiment, the animals were euthanized, and a number of cardiomyopathy indices were investigated. The diabetic rats exhibited a momentous increase in hyperlipidemia, lipid peroxidation as well as a significant (p < 0.05) decline in antioxidant enzyme activities. The serum creatine kinase MB (CK-MB), C-reactive protein (CRP), cardiac troponin I, tumour necrosis factor-alpha (TNF-α) and urotensin II expression revealed a significant (p < 0.05) upsurge in diabetic rats. Also, the expression of GLUT4 and fatty acid-binding protein 3 (FABP3) were significantly (p < 0.05) reduced in diabetic rats. However, at the conclusion of the experimental trial ST significantly (p < 0.05) attenuated hyperlipidemia, oxidative stress biomarkers by augmenting the antioxidant enzyme activities and decrease in lipid peroxidation, ameliorated CK-MB, CRP, cardiac troponin I, TNF-α, and urotensin-II levels, and improved GLUT4 and FABP3 expressions. Similarly, the administration of ST prevented histological alterations in the heart of diabetic animals. Therefore, the obtained results suggest that ST could mitigate DCM in streptozotocin-induced diabetic rats.

Background: This study sought to investigate anti-hyperglycemic potentials of free and bound phenolic-rich extracts of Andrographis paniculata ( A. paniculata ) leaves, commonly called "king of the bitter", a plant locally employed in folkloric alternative medicine ., Method: In vitro antioxidant potentials such as total phenolic and flavonoid contents were evaluated in addition to phosphomolybdenum reducing total antioxidant activity in bound and free polyphenol-rich extracts of A. paniculata. Also, following induction of diabetes through a single intraperitoneal injection of freshly prepared alloxan monohydrate (150 mg/kg body weight, b.w), diabetic rats were divided into seven (7) treatment groups with six rats each ( n  = 6) i.e. group 1 (normal control), 2 (diabetic untreated), 3 (5 mg/kg glibenclamide -treated control), while 4-7 were administered 50 and 100 mg/kg b.w of free and bound phenolic extracts of A. paniculata , respectively for twenty-one (21) days., Results: There was a significant ( p  < 0.05) difference in hematological indices, hepatic biomarkers, total protein, antioxidant enzymes activities, total thiol and fasting blood glucose levels of diabetic groups administered polyphenolic-rich extracts of A. paniculata compared to diabetic untreated control. Similarly, serum insulin levels, hexokinase and glucose-6-phoshatase activities were significantly ( p  < 0.05) improved in phenolic-rich extracts of A. paniculata -treated diabetic groups compared to diabetic untreated control. A significant ( p  < 0.05) reduction was as well observed in the levels of inflammatory biomarkers such as interleukin-6 (IL-6) and tumor necrosis factor (TNFα) among extract of A. paniculata administered diabetic groups compared diabetic untreated group., Conclusions: Anti-hyperglycemic activities demonstrated by polyphenolic-rich extracts of A. paniculata when compared to glibenclamide and normal control, could possibly have been occasioned by β-cell protection, restoration of glycolytic enzymes as well as mitigation of inflammatory markers via antioxidant defensive/protective properties of the extracts., Competing Interests: Conflict of interestThe authors of the manuscript declare no conflict of interest concerning the work., (© Springer Nature Switzerland AG 2020.)

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., (© 2020 Society of Chemical Industry.)

Objectives This study was designed to examine the in vitro inhibitory activities of vital enzymes related to diabetes mellitus and different biochemical parameters of Phoenix dactylifera fruit based-diet in alloxan-induced diabetic rats. Methods The aqueous extract of P. dactylifera fruit based-diet was prepared and used for determination of in vitro antioxidants as well as α-amylase and α-glucosidase inhibitory activities using standard procedures. Also, 30 albino rats were induced by a single intraperitoneal injection of 150 mg/kg body weight of alloxan and grouped into A-D as normal rats placed on Dioscorea rotundata based-diet, diabetic control rats placed on D. rotundata based-diet, diabetic rats placed on D. rotundata based-diet and administered metformin orally per day, and diabetic rats placed on P. dactylifera fruit based-diet respectively. The animals were sacrificed on the fourth week of the experiment, and different biochemical parameters were evaluated. Results The P. dactylifera fruit based-diet extract demonstrated antioxidative potentials and inhibition against α-amylase and α-glucosidase activities in a dose-dependent manner. In addition, diabetic rats placed on the P. dactylifera fruit based-diet revealed significant (p<0.05) increase in body weight, insulin and glycogen levels, antioxidant enzyme activities, GLUT 2 and high density lipoprotein (HDL) concentrations when compared with the diabetic control group. Also, diabetic rats placed on P. dactylifera fruit based-diet indicate significant (p<0.05) reduction in fasting blood glucose, lipid peroxidation, cytokines levels, some gluconeogenesis enzyme activities, cholesterol, triglycerides, low-density lipoproteins and very low-density lipoproteins concentrations compared to the diabetic control animals. Conclusion This diet could be an alternative nutraceutical means of managing diabetes mellitus and its complications.

Objective: This study was designed to evaluate the protective effect of aqueous extract of Solanum macrocarpon Linn leaf in the brain of an alloxan-induced rat model of diabetes., Methods: The experimental model of diabetes was induced by a single intraperitoneal injection of freshly prepared alloxan. Rats were then divided into six groups: normal control, diabetes control, diabetes group treated with metformin, and three diabetes groups treated with different concentrations of S. macrocarpon . Rats were sacrificed on day 14 of the experiment and different brain biochemical parameters were assessed and compared between groups., Results: Administration of different doses of S. macrocarpon leaf aqueous extract was associated with significantly reduced levels of fasting blood glucose, lipid peroxidation, neurotransmitters, cholinesterases, cyclooxygenase-2 and nitric oxide compared with diabetes control rats. In addition, antioxidant enzyme activities were significantly increased in diabetes rats administered 12.45, 24.9 and 49.8 mg/kg body weight of S. macrocarpon versus diabetes control rats., Conclusion: Aqueous extract of S. macrocarpon Linn leaf may be useful in the management of diabetic neuropathy.

Background: Gongronema latifolium leaf is used traditionally to treat diabetes and other diseases. The present study aimed to provide the modulatory effect of G. latifolium on hyperglycemia, inhibitory effect of redox imbalance and inflammation in alloxan-induced nephropathy in Wistar rats., Methods: Alloxan monohydrate was used to induce diabetes by an intraperitoneal injection of (150 mg/kg). Three diabetic groups were administered aqueous leaf extract of G. latifolium at 6.36, 12.72 and 25.44 mg/kg bodyweight (BW) respectively; a group was administered with metformin (5 mg/kg BW), while the other two were served as positive and negative control. Thereafter, fasting blood glucose, antioxidant enzymes, malondialdehyde (MDA) level, interleukin 2 and 6 were determined., Results: G. latifolium leaf significantly ( p  < 0.05) reduced the alloxan-induced increases in blood glucose, MDA, interleukin 2 and interleukin 6 level and increased the alloxan-induced decreases in superoxide dismutase, catalase, glutathione peroxidase, glutathione reduced and glutathione transferase activity. All these changes compared with those of metformin-treated diabetic rats., Conclusion: The data from this study suggest that G. latifolium modulates glucose homeostasis as well as inhibiting redox imbalance and inflammation in diabetic rats, which may be attributed to the effects of its phytochemical constituents such as saponins, flavonoids and alkaloids. It also indicated that inhibition of inflammatory cytokines and redox imbalance are likely mechanisms by which G. latifolium leaf exert its antidiabetic action., Competing Interests: Conflict of interestAuthors declare no conflict of interest all through the compilation of this manuscript., (© Springer Nature Switzerland AG 2020.)

Introduction: Watermelon is one of the commonly eaten fruit in most homes in Nigeria and has been used in the management of diabetes mellitus traditionally. This study was carried out to explore the antidiabetic potential of watermelon ( Citrullus lanatus ) juice in alloxan-induced diabetic rats., Methods: Watermelon juice was used for the determination of in vitro parameters such as 1,1-diphenyl-2-picryl-hydrazil (DPPH), nitric oxide and ferric reducing antioxidant potential (FRAP) as well as phytochemicals such as total phenol, total flavonoids. In vitro , α-glucosidase and α-amylase inhibitory activities were also accessed using standard procedures. Diabetes was induced in the rats by a single intraperitoneal (I.P) injection of freshly prepared alloxan (150 mg/kg body weight). The animals were randomly grouped into five groups of normal control, untreated diabetic control, diabetic rats administered 200 mg/kg body weight of metformin, diabetic rats administered 500 mg/kg body weight of watermelon ( Citrullus lanatus ) juice and diabetic rats administered 1000 mg/kg body weight of watermelon juice. The rats were sacrificed on the 14th day of the experiment and various in vivo biochemical parameters were also evaluated in the serum and tissue homogenates of diabetic rats., Results: The watermelon juice exhibits anti-oxidant properties and inhibitory activities against α-glucosidase and α-amylase in a dose-dependent manner. Added to this, the administration of different doses of the watermelon juice significantly ( p  < 0.05) reduced the fasting blood glucose level, serum lipid profile, glucose-6-phosphatase, lipid peroxidation and anti-inflammatory activities in alloxan-induced diabetic rats. There was a significant ( p  < 0.05) increase in antioxidant enzyme activities, hexokinase activity as well as glucose transporters (GLUT 2 and GLUT 4) levels in diabetic rats administered different doses of Citrullus lanatus., Conclusion: Taken together, this study demonstrates that watermelon ( Citrullus lanatus ) juice exhibits its antidiabetic potential in experimental diabetic animal model via multiple pathways involving modulation of glucose transporters, anti-inflammatory activities as well as antioxidant defense system and inhibition of α-glucosidase and α-amylase. This suggests that the watermelon ( Citrullus lanatus) juice may have a useful clinical application in the management of diabetes mellitus and its metabolic complications if developed as adjuvant therapy., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© Springer Nature Switzerland AG 2020.)

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.