EVALUATION OF ANTI-DIABETIC ACTIVTY OF DIFFERENT EXTRACTS OF MYRISTICA FRAGRANS HOUTT: IN VITRO AND IN SILICO STUDIES

Objective: This study is aimed to evaluate the anti-diabetic effect of sequentially extracted (hexane, dichloromethane, ethyl acetate, and ethanol) Myristica fragrans houtt (mace) through in vitro and in silico studies.Methods: The in vitro anti-diabetic effect of the sequentially extracted plant were evaluated for its alpha-amylase inhibitory activity and the potential binding was studied by in silico studies using Schrödinger Maestro.Results: All extracts showed dose dependent alpha-amylase inhibitory effect. At concentration 500 µg/ml, all the extracts showed more than 60% inhibition of the alpha-amylase enzyme and the highest inhibition (81.30%) at 500 µg/ml was observed in DCM extract of mace. Potential compounds were identified by in silico molecular docking studies of alpha-amylase with phytocomponents from DCM extract. Among the top three compounds from virtual screening, induced fit docking studies revealed 2,5-bis(3,4-dimethoxyphenyl)-3,4-dimethyloxolane possessed better binding affinity when compared with the drug metformin.Conclusion: The obtained in vitro and in silico results suggest that all extracts of Myristica fragrans can be used successfully for the management of diabetes mellitus.Keywords: Myristica fragrans, Mace, Sequential extraction, Alpha-amylase, Molecular docking

Comparative Evaluation of Three Different Systems used for Retreatment of Teeth Filled with Gutta Percha and Bioceramic based Root Canal Sealer: A Randomized In Vitro study

Endodontic retreatment has become necessary nowadays in practice due to various reasons which would have led to the failure of the primary endodontic treatment: which could be pathologic or iatrogenic. In those cases, which require retreatment, the removal of previous filling material is essential which may pose hindrance in disinfection and debridement of the canal for providing better treatment. Various methods can be adopted for the removal of obturation materials from the canals, like hand and rotary retrieval methods, with or without the use of chemical solvents. In our study, effective removal of Gutta Percha and Bioceramic sealer using three different retreatment systems ProUltra Ultrasonic retreatment tips, Protaper Universal retreatment files, and R Endo retreatment files was compared. It is found that R Endo files are most efficient, followed by Protaper Universal retreatment files. However further in-vivo and long term follow up studies required to substantiate our study results. CONCLUSION: Within the parameters of this in vitro study it can be concluded that none of the file system completely removed the Gutta-percha and MTA Fillapex sealer from the root canals. However, R Endo files are most efficient, followed by Protaper Universal retreatment files. Whereas Proultra ultrasonic retreatment tip were least effective in removing the Guttapercha from the root canal system

COMPUTATIONAL DOCKING AND IN SILICO ANALYSIS OF POTENTIAL EFFLUX PUMP INHIBITOR PUNIGRATANE

Objective: Efflux-mediated resistance is a growing therapeutic complication as it reduces the efficacy of antibiotics. In gram-negative bacteria like E. coli and K. pneumoniae, this can be overcome with the help of efflux pump inhibitors (EPI) targeted at the transporter protein AcrB that plays a key role in binding to antibiotics. Our study focuses on the potential EPI Punigratane isolated from the rind of Punica granatum. Using computational docking analysis and in silico analysis, our aim is to determine whether Punigratane has the ability to interact and inhibit the AcrB pump and whether it has drug viability.Materials: Computational docking analyses were carried out using the online platforms Mcule and PatchDock. Drug-likeness and classification of Punigratane was predicted using online tools PreADMET and SuperPred. Admet SAR and Toxicity Checker at Mcule were used to predict ADME (absorption, distribution, metabolism, and excretion) and overt toxicity properties.Results: Punigratane was computationally docked with 57 AcrB crystal structures available at the PDB database to determine whether it could bind to the active site regions. It was found to bind in the periplasmic region close to the substrate bile acid where it is thought to bring about inhibition by steric hindrances. When docked with AcrB mutant (AcrB N109A), it was found to bind in the same periplasmic site as the substrates (EtBr, Rhodamine 6G, Ciprofloxacin, Bile acid) as well as the inhibitor (phenylalanine-arginine β-naphthylamide-PaβN). When docked in the active site of the inhibitor MBX2319, it was found to have a comparable docking score as well as the same hydrophobic interactions as the inhibitor. In silico analysis showed that Punigratane exhibited a drug-likeness to the inhibitor MBX2319 and that its drug classification is similar to antimicrobial agents. It was also found be a potential drug due to its intestinal absorption, increased bioavailability and non-toxic nature.Conclusion: Therefore our report shows that Punigratane could be a potential drug candidate that inhibits efflux activity by interacting and inhibiting the AcrB efflux pump.Â

ANTI-INFLAMMATORY ACTIVITY OF SYZYGIUM AROMATICUM SILVER NANOPARTICLES: IN VITRO AND IN SILICO STUDY

  Objective: In the present study, antioxidant and anti-inflammatory activity of Syzygium aromaticum (clove) silver nanoparticles (clove AgNP's) was evaluated.Methods: Gas chromatography-mass spectrometry technique was used to identify the compounds present in the aqueous extract of clove. Fourier transform infrared (FT-IR) analysis was done to characterize the clove silver AgNP's. 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay was performed to evaluate the antioxidant property of nanoparticles (0.05 and 0.25 mg/ml) and aqueous extracts (0.05, 0.1, and 0.25 mg/ml) of clove. The anti-inflammatory property of the clove AgNP's was determined by inhibition of protein denaturation and downregulation of interleukin-1 beta. In silico molecular docking studies was performed using Schrodinger Maestro software.Results: Eugenol was found to be highest with 16.27%. The AgNP's exhibited dose-dependent antioxidant property. AgNP's scavenged 80% of radical at the concentration of 0.25 mg/ml. The scavenging activity of AgNP's markedly increased when compared to aqueous extract at the same concentration. Inhibition of protein denaturation assay also revealed AgNP's showing the highest activity (66%) when compared with drug aspirin (55%) and aqueous extract (56%). In the enzyme-linked immunosorbent assay (ELISA) method, AgNP's showed better inhibition (80%) when compared to aqueous extract (60%). Among 15 compounds, two compounds (eugenol and methyl 14-methylpentadecanoate) showed good glide energy, docking score, and hydrogen-bonded active site interactions with the protein interleukin-1 beta.Conclusion: As AgNP's were more active than the aqueous extract, it may be considered for pharmacological activity against inflammatory disorders