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- Background: Diabetes mellitus remains a significant global health challenge, with traditional medicinal plants offering promising therapeutic potential. Brachystegia eurycoma has been traditionally employed in African medicine for diabetes management, yet its mechanisms of action remain poorly understood. Purpose: To evaluate the antidiabetic potential and elucidate the molecular mechanisms of B. eurycoma leaf extract through both In vitro and In vivo studies. Methods: The ethanol extract was assessed for antioxidant activity (ABTS, DPPH, FRAP), α-amylase and α-glucosidase inhibition, and phytochemical content. Alloxan-induced diabetic rats received oral doses (100–400 mg/kg) for 21 days. Multiple parameters, including glycemic indices, insulin, glycogen, metabolic enzymes, antioxidant markers, inflammatory mediators, and lipid profiles, were evaluated. Results: The extract demonstrated significant antioxidant activity (73.32 % DPPH, 58.88 % ABTS inhibition) with high phenolic (348.8 mg GAE/100 g) and flavonoid (158.26 mg QE/kg) content. In diabetic rats, 400 mg/kg treatment reduced hyperglycemia by 31.5 %, increased insulin by 82 %, and enhanced glycogen by 84 %. Hexokinase and glucose-6-phosphate dehydrogenase activities improved to 11 % and 52.5 % of normal control, while glucose-6-phosphatase decreased to 55 % of diabetes control. Treatment significantly reduced inflammatory markers (TNF-α, IL-6) and improved lipid profiles with a marked increase in HDL and reduction in LDL and triglycerides (p < 0.05). Conclusion: B. eurycoma leaf extract exhibits multifaceted antidiabetic effects through antioxidant activity, carbohydrate-metabolizing enzyme inhibition, and metabolic regulation, supporting its traditional use and warranting further clinical investigation.
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- 2023| AMG Transcend Associ...Diabetes mellitus (DM) is by far the most common metabolic disease impacting human health, and Type II diabetes (T2DM) accounts for almost all occurrences of diabetes. This work examined the anti-diabetic efficacy of Brachystegia eurycoma compounds against druggable proteins associated with T2DM and its complications. Fourteen proteins were identified in the literature as T2DM treatment targets and downloaded from the protein data bank. Preliminary screening of the compounds with the protein targets via molecular docking studies showed that the compounds, notably quercetin, kaempferol, and catechin, had high selectivity for GLUT1, aldose reductase, and GLP-1 receptor. Eleven compounds from the plants were chosen as hits based on their favorable binding energies with the proteins. Following molecular docking studies, binding free energy, DFT calculation, ADMET predictions, and QSAR were used to examine further the drug-likeness, efficacy, toxicity, stability, and inhibitory/agonizing prowess of these compounds. The findings in this study showed that these eleven bioactive compounds, which belong to the group of flavonoids and phenolic acids that formed stable complexes with the three proteins, had moderate/low toxicity, are bio-orally available and non-inhibitors of some/all of the CYP450 isozymes. Using trustworthy correlation coefficients (R2), the predicted QSAR models demonstrated the potency of the compounds to function as inhibitors (pIC50) of aldose reductase and GLUT1 and as agonists (pEC50) of GLP-1R. According to DFT calculation of frontier molecular orbitals (FMOs) and global descriptive parameters, it was shown that Quercitrin is the most chemically inert molecule, whereas chlorogenic acid is the most reactive compound. This experimental approach may be utilized to develop drugs that can modulate proteins associated with T2DM without causing off-target effects, as shown in this research.
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- Diabetes mellitus (DM) is a metabolic condition characterized by chronic hyperglycemia caused by insulin secretion and action deficiencies. Type 2 DM results from impaired insulin secretion by β cells of the pancreas and unresponsive signals between insulin-target tissues and insulin. Most drugs used in treating DM have one or more negative side effects and are primarily focused on lowering blood glucose levels rather than addressing the underlying mechanisms that cause DM. Therefore, developing new drugs to address these underlying causes is a priority. This study seeks to explore the antidiabetic roles of phytochemicals from Chrysobalanus orbicularis Hook. f. (Chrysobalanaceae) using in silico techniques to identify a novel regimen for DM. High-performance liquid chromatography (HPLC) analysis of C. orbicularis identified four bioactive compounds (sapogenin, delphinidin, cyanidin, and petunidin). To screen and find acceptable potential hit compound(s), these compounds were subjected to molecular docking to decipher their interactions with some proteins identified in the literature as being involved in the pathophysiology of DM (dipeptidyl peptidase IV, alpha-amylase, glucagon-like peptide−1 receptor, alpha-glucosidase, poly[ADP-ribose] polymerase 1, and G-protein coupled bile acid receptor 1). Petunidin had the best interaction with most of the proteins based on the precision docking score and MM-PBSA analysis. More importantly, parameters for discovering drugs for biotherapeutic candidates, viz., distribution, absorption, metabolism, toxicity, and excretion, were calculated for petunidin. Our findings suggest that petunidin could be a promising new therapeutic target for treating DM.
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- 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.
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- Skin aging and wrinkle formation are processes that are largely influenced by the overexpression of enzymes like tyrosinase, elastase, and collagenase. This study aimed to validate the skin anti-aging properties of phytochemicals from Peperomia pellucida (PP) as well as its attendant mechanism of action. Compounds previously characterized from PP were retrieved from the PubChem database and docked to the active sites of tyrosinase, elastase, and collagenase using Schrödinger’s Maestro 11.5 and AutoDock tools to predict compounds with the best inhibitory potential to block these enzymes in preventing skin aging. It was observed that our hit compounds had favorable affinity and displayed key interactions at the active sites of these enzymes similar to those of the standards. With elastase, we observed key interactions with the amino acids in the S1 sub-pocket (especially ALA-181), Zn chelation, and histidine residues, which are key for inhibitory activity and ligand stability. The hit compounds showed H-bonds with the key amino acids of collagenase, including LEU-185 and ALA-186; phlobaphene and patuloside B were found to have better docking scores and inhibition constants (Ki) (−12.36 Kcal/mol, 0.87 nM and −12.06 Kcal/mol, 1.45 nM, respectively) when compared with those of the synthetic reference compound (−12.00 Kcal/mol, 1.67 nM). For tyrosinase, our hit compounds had both better docking scores and Ki values than kojic acid, with patuloside B and procyanidin having the best values of −9.43 Kcal/mol, 121.40 nM and −9.32 Kcal/mol, 193.48 nM, respectively (kojic acid = −8.19 Kcal/mol, 898.03 nM). Based on this study, we propose that acacetin, procyanidin, phlobaphene, patulosides A and B, palmitic acid, and hexahydroxydiphenic acid are responsible for the anti-aging effects of PP on the skin, and that they work synergistically through a multi-target inhibition of these enzymes.
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- Background The increasing global incidence of breast cancer calls for the identification of new therapeutic targets and the assessment of possible neem-derived inhibitors by means of computational modeling and integrated genomic research. Methods Originally looking at 59,424 genes throughout 42 samples, we investigated gene expression data from The Cancer Genome Atlas—Breast Cancer (TCGA-BRCA) dataset. We chose 286 genes for thorough investigation following strict screening for consistent expression. R’s limma package was used in differential expression analysis. The leading candidate’s protein modeling was done with Swiss-ADME and Discovery Studio. Molecular docking studies, including 132 neem compounds, were conducted utilizing AutoDock Vina. Results Among the 286 examined, mitochondrially encoded cytochrome C oxidase III (MT—CO3) turned out to be the most greatly overexpressed gene, showing consistent elevation across all breast cancer samples. Protein modeling revealed a substantial hydrophobic pocket (volume: 627.3 Å3) inside the structure of MT—CO3. Docking investigations showed five interesting neem-derived inhibitors: 7-benzoylnimbocinol, nimolicinol, melianodiol, isonimocinolide, and stigmasterol. Strong binding affinities ranging from −9.2 to −11.5 kcal/mol and diverse interactions with MT—CO3, mostly involving the residues Phe214, Arg221, and Trp58, these molecules displayed. With hydrophobic interactions dominant across all chemicals, fragment contribution analysis revealed that scaffold percentage greatly influences binding effectiveness. Stigmasterol revealed greater drug-likeness (QED = 0.79) despite minimal interaction variety, while 7-benzoylnimbocinol presented the best-balanced physicochemical profile. Conclusion Connecting traditional medicine with current genomics and computational biology, this work proposes a methodology for structure-guided drug design and development using neem-derived chemicals and finds MT—CO3 as a potential therapeutic target for breast cancer.
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- 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.
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- Objective: This study investigated the protective effects of flavonoid-rich extracts from Hibiscus sabdariffa leaves on testicular cumulative reproductive function biomarkers in streptozotocin (STZ)-induced diabetic rats. Methods: Rats were induced with 40 mg/kg body weight (bwt) STZ intraperitoneally (i.p.), after which they were administered either a low (150 mg/kg bwt) or a high (300 mg/kg bwt) dose of flavonoid-rich extracts from H. sabdariffa leaves. Testicular redox biomarkers, reproductive hormone biomarkers, and relative gene expression levels of PDE-5 and iNOS were assessed. Additionally, histological data, glucose levels, G6PDH activity, and hydroxysteroid dehydrogenase activities (3β-HSD and 17β-HSD) were analyzed. Results: H. sabdariffa leaf extract was promising for restoring redox balance, normalizing reproductive hormone levels, modulating gene expression, and regulating various biochemical parameters related to testicular function. Conclusion: These data suggest a potential therapeutic role of H. sabdariffa leaves in mitigating the testicular dysfunction associated with diabetes.
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- 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.
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- Background: The genus Pennisetum contains remarkable natural bioactive components, and its 140 species are widely distributed in tropical and subtropical countries, where they are frequently used for therapeutic purposes such as the treatment of dysentery, fever, diabetes, and abdominal pain by indigenous people. However, the available information for this genus has not been thoroughly researched in terms of their bioactive principles and extracts. Aim of the review: The current review provides a profound perception, enhanced understanding, and comprehensive information on the traditional uses, phytochemical com- pounds, and biological activities of the genus Pennisetum, as well as toxicological perspectives. Furthermore, the significance of ethnopharmacological uses, application, and the beneficial potential of Pennisetum species for the management of a variety of diseases were thoroughly discussed. Materials and methods: The significant data of Pennisetum species was obtained through a thorough review of scientific articles published in a variety of databases, including Elsevier, Wiley, Web of Science, Springer, PubMed, Taylor and Francis, and Google Scholar. Furthermore, PhD and MSc theses were used in compiling and evaluating data obtained. Results: The ethnopharmacological applications of Pennisetum genus plants in various countries were established through detailed analysis of the aforementioned databases and thesis. So far, only a few species’ chemical compositions and a total of 35 metabolites (excluding amino acids and fatty acid constituents) have been studied, including saponins, tannins, flavonoids, alkaloids, steroids, anthocyanin phenols, terpenoids, and others. The crude extracts were found to have antioxidant, antimicrobial, anti- cytotoxic, anti-hypertensive, and anti-inflammatory properties. Furthermore, the significance of ethnopharmacological applications, application, and the positive potential of Pennisetum species for the management of a variety of disorders was thoroughly examined.
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