Antidiabetic effect of flavonoid from Rumex vesicarius on alloxan induced diabetes in Male Albino Wistar rats and its validation through in silico molecular docking and dynamic simulation studies.

The leaves of Rumex vescarius L. are used locally to treat diabetes, a chronic illness. A flavonoid called Luteolin from R. vesicarius was chosen to explore for the antidiabetic potential through the in vivo antidiabetic test against male albino Wistar rats that had been induced with diabetes due to alloxan. Additionally, docking screening was carried out with the aid of autodock software to identify probable moiety that might be in charge of its anti-diabetic effect. Given at a dose of 100 mg/kg body weight, luteolin from R. vesicarius leaves had a significant (p < 0.05) hypoglycaemic impact after just one week. The blood glucose level significantly decreased during the third week (p < 0.05). All provided doses of luteolin from R. vesicarius leaves resulted in a reduction, however on all study days, the highest concentration (400 mg/kg body weight) produced the biggest reduction. The results of luteolin's molecular docking and dynamic modelling studies with a variety of targets revealed significant binding interactions at the active site binding pocket, with the target α-glucosidase having the highest binding affinity (-9.35 kcal/mol). In conclusion, the plant and the flavonoid luteolin it contains have potent anti-diabetic properties, possibly through an interaction with the enzyme α-glucosidase.

Nephroprotective Effects of Mycophenolate Mofetil and Glibenclamide on Streptozotocin-induced Diabetic Renal Injury in Rats: An Experimental Study.

Diabetic renal injury is a microvascular complication associated with inflammation and oxidative stress, culminating in renal dysfunction. Conventionally, it is treated with hypoglycemic agents to address metabolic perturbations. However, the way to mitigate immunological, inflammation, and oxidative stress have seldom been studied. Hence, in the present study, the nephroprotective role of immunosuppressive and anti-inflammatory drugs, mycophenolate mofetil (MMF) in combination with the oral hypoglycemic agent glibenclamide, on streptozotocin (STZ)- induced diabetic renal damage was studied. Bodyweight, fasting blood glucose, and glycosylated hemoglobin levels were altered in the diabetic rats. Furthermore, renal injury was indicated by abnormal levels of urinary protein and creatinine and serum markers of renal function in diabetic rats. Hyperglycemia-induced oxidative stress and inflammation were also observed in the diabetic rats. The combination of MMF and glibenclamide treatment significantly attenuated the abnormal effects of hyperglycemia, oxidative stress, and inflammation-induced renal injury in diabetic rats. Histopathological studies confirmed the nephroprotective role of MMF and glibenclamide by reversing renal injury in diabetic rats. The present study suggests that MMF and glibenclamide have a protective role in STZ-induced diabetic renal damage.

In silico toxicity prediction, molecular docking studies and in vitro validation of antibacterial potential of alkaloids from Eclipta alba in designing of novel antimicrobial therapeutic strategies.

The rapid emergence of various drug resistance and unfavourable aliphatic medication side effects endangers people's health. Phytocompounds with antibacterial activity and less harmful effects are known to be present in medicinal plants. Alkaloids from Eclipta alba were tested for their in vitro antibacterial capabilities and in silico docking studies against pathogenic bacteria and their target proteins in the current investigation. The alkaloid compounds verazine, ecliptine, 4-hydroxyverazine, 20-Epi-4beta-hydroxyverazine and hydroxyverazine were subjected to molecular docking studies to determine the method of binding as well as potential interactions and the docking score. The in vitro antibacterial activity of verazine alkaloid was assessed against two gram-positive and two gram-negative bacteria. Verazine alkaloid has the best inhibitory ability against DNA gyrase of E. coli (ΔG= -8.44 kcal/mol) and dihydrofolate reductase (DHFR) of S. aureus (ΔG= -10.04 kcal/mol), according to docking studies. Verazine shown substantial in vitro antibacterial activity in this investigation against all test bacteria, with MIC and MBC values of 31.25 and 62.50 µg/mL for S. aureus and 15.63 and 31.25 µg/mL for B. cereus, respectively. The results of this work highlighted the value of unique alkaloid compounds from E. alba, which may offer effective antibacterial agents and DNA gyrase, DHFR inhibitors due to their novel structural properties capable of combating antimicrobial resistance. These findings call for more investigation into the compounds' function as antibacterial agents, as well as their unique-binding locations and mechanisms.

In silico prediction of mozenavir as a potential drug for SARS-CoV-2 infection via binding multiple drug targets.

Since the epidemic began in November 2019, no viable medicine against SARS-CoV-2 has been discovered. The typical medication discovery strategy requires several years of rigorous research and development as well as a significant financial commitment, which is not feasible in the face of the current epidemic. Through molecular docking and dynamic simulation studies, we used the FDA-approved drug mezonavir against the most important viral targets, including spike (S) glycoprotein, Transmembrane serine protease 2 (TMPRSS2), RNA-dependent RNA polymerase (RdRp), Main protease (Mpro), human angiotensin-converting enzyme 2 (ACE-2), and furin. These targets are critical for viral replication and infection propagation because they play a key role in replication/transcription and host cell recognition. Molecular docking revealed that the antiviral medication mozenavir showed a stronger affinity for SARS-CoV-2 target proteins than reference medicines in this investigation. We discovered that mozenavir increases the complex's stability and validates the molecular docking findings using molecular dynamics modeling. Furin, a target protein of COVID-19, has a greater binding affinity (-12.04 kcal/mol) than other COVID-19 target proteins, forming different hydrogen bonds and polar and hydrophobic interactions, suggesting that it might be used as an antiviral treatment against SARS-CoV-2. Overall, the present in silico results will be valuable in identifying crucial targets for subsequent experimental investigations that might help combat COVID-19 by blocking the protease furin's proteolytic activity.

Phenolic compounds as promising drug candidates against COVID-19 - an integrated molecular docking and dynamics simulation study.

Piper was used to cure certain human afflictions. It has various biological processes in literary works. Our work aims to identify and to explain the molecular base in silico in phytoderived anti-viral compounds in Piper nigrum against the major protease enzyme COVID-19. The thesis includes docking and molecular dynamic modelling review of 8 phenolic compounds from Piper extracted from the PubMed database. Docking analysis with Autodock programme was conducted. Our analysis reveals that the two Piper phytochemicals are very susceptible to the COVID-19 major protease enzyme. These phyto-compounds from piper may use contemporary techniques to create a stable drug or help the detection of lead. In order to assess their efficacy against COVID-19, identified hit compounds can be taken further in vitro and in vivo tests.

Rilpivirine inhibits SARS-CoV-2 protein targets: A potential multi-target drug.

BACKGROUND: COVID-19 disease caused by SARS-CoV-2 is lacking efficient medication although certain medications are used to relief its symptoms. OBJECTIVES: We tested an FDA-approved antiviral medication namely rilpivirine to find a drug against SARS-CoV-2. METHODS: The inhibition of rilpivirine against multiple SARS-CoV-2 therapeutic targets was studied using in silico method. The binding attraction of the protein-ligand complexes were calculated using molecular docking analysis. RESULTS: Docking rilpivirine with main protease (Mpro), papin like protease (PLpro), sprike protein (Spro), human angiotensin converting enzyme-2 (ACE2), and RNA dependent-RNA polymerase (RdRp) yielded binding energies of -8.07, -8.40, -7.55, -9.11, and -8.69 kcal/mol, respectively. The electrostatic interaction is the key force in stabilizing the RdRp-rilpivirine complex, while van der Waals interaction dominates in the ACE2 rilpivirine case. Our findings suggest that rilpivirine can inhibit SARS-CoV-2 replication by targeting not only ACE2, but also RdRp and other targets, and therefore, it can be used to invoke altered mechanisms at the pre-entry and post-entry phases. CONCLUSION: As a result of our in silico molecular docking study, we suggest that rilpivirine is a compound that could act as a powerful inhibitor against SARS-CoV-2 targets. Although in vitro and in vivo experiments are needed to verify this prediction we believe that this antiviral drug may be used in preclinical trials to fight against SARS coronavirus.

Evaluation of the andrographolides role and its indoleamine 2,3-dioxygenase inhibitory potential and attendant molecular mechanism against STZ-induced diabetic rats.

The study is to scrutinize andrographolides with Indoleamine 2,3-dioxygenase (IDO) inhibitory potential, its molecular mechanism against streptozotocin (STZ) diabetic retinopathy (DR) in Wistar rats. Oxidative stress markers such as Kynurenine metabolites, retinal histopathological changes have been studied. Further, IDO gene expression and docking studies have been performed. Andrographolide treated rats have been reducing the level of thiobarbituric acid reactive substances and protein carbonyls Kynurenine metabolites with an improvement in the level of GSH and expression of IDO as revealed by morphological changes in inner and outer nuclear layer of the retina. The current results of this study have been generated information about an activity of the andrographolide in the essential pocket of IDO. Our results explain, involving IDO and andrographolide would constitute an attempt to identify natural products with therapeutic value and further studies in this direction would be of immense significance in the administration of diabetes and its related problems.