Search

Topical delivery of local anaesthetic drugs such as Lidocaine HCl using carriers and novel nanotechnology can enhance effective drug permeation through the skin into deeper layers and exhibit desirable duration of action. The present study was aimed to formulate and evaluate Lidocaine HCl loaded cubosomes (LHLCs) for sustained therapeutic topical action. Cubosomes emanated as favourable means for the delivery of the drug. LHLCs were prepared by top-down technique using lipid and polymer. Eight formulations of LHLCs were prepared using different concentrations of glyceryl monooleate (GMO) and Poloxamer 407 (P-407). Local anaesthetics create loss of sensation in particular region of the body by inhibiting impulse generation and propagation. Lidocaine HCl is most commonly used amino amide local anaesthetic. It is used as local, topical, intravenous, epidural, peripheral and spinal anaesthesia. The prepared cubosomal dispersions were evaluated to determine surface morphology, particle size, poly dispersibility index (PDI), zeta potential, entrapment ability, tissue distribution studies, and in vitro drug release studies. Scanning Electron Microscopic analysis confirmed that drug was encapsulated in bicontinuous structure. The maximum entrapment efficiency was found to be 89.85±1.1% with vesicle size as 228±2.1nm, charge as -5.68±2.7, PDI as 0.295 and 98.83%± 0.12 in vitro drug release at the end of 12 hr for F7 formulation, which was confirmed as optimized cubosomal dispersion.

Objectives This research aimed to evaluate the antiangiogenic activity of isolated flavonoid 4a,5,8,8a-tetrahydro-5-hydroxy-3,7,8-trimethoxy-2-(3,4-dimethoxyphenyl) chromen-4-one (TMF) from Tabebuia chrysantha. STAT3-MMP9 signalling is a signal transduction mechanism that promotes angiogenesis in various cancers. Methods The tumour xenografting chicken embryo chorioallantoic membrane (CAM) model-based ex vivo assay was used to evaluate the activity of TMF. The Western blot, densitometric analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to evaluate the activity of the MMP9. Zebrafish embryos were used to evaluate embryotoxicity, and in vitro free radical scavenging activity of flavonoid was also elucidated. Key findings This research assessed the high level of STAT3, p-ERK, VEGF-R and MMP9 in the tissue extract of the control group, and also, the suppression of angiogenesis in the treatment groups was due to scavenged ROS and RNS, dephosphorylation of STAT3 and ERK, and suppression of MMP9 gene expression. Conclusion The isolated flavonoid named TMF from T. chrysantha functions as specific regulators of target proteins of angiosarcoma. The STAT3-MMP9 signalling may be used as an effective prognostic marker of angiosarcoma.

Pastinaca sativa belonging to the family Apiaceae, is a tropical tree used in many countries as a herbal drug for the care of diabetic patients. However, the methodical rationale for this medical use is very limited. The aim of this analysis was to examine the antidiabetic activity of the Pastinaca sativa methanolic extract and the possible mechanisms underlying that activity. The extract hypoglycemic behavior was investigated in typical diabetic rats induced with alloxan. Finally, an effect of the Pastinaca sativa extract (Crude extract of Pastinaca sativa-CEPS) on the activity of α-amylase and α-glucosidase was examined in vitro. CEPS showed IC50 equal to 91.69 ± 1.5 μg/mL for α-amylase enzyme inhibition activity. Normal acarbose (control) demonstrated IC50 equal to 83.25 ± 1.28 μg/mL. CEPS displayed IC50 values of 88.05 ± 1.25 μg/mL for α-glucosidase enzyme. Under similar laboratory conditions, acarbose displayed an IC50 value of 51.00 ± 1.23 μg/mL. CEPS exhibited IC50 less than 100μg/mL would be considered as healthy. The extract at 400 mg/kg greatly decreased the region under the blood glucose level curve in a typical rats test for oral glucose tolerance. A single dose of the extract decreased significantly in the alloxan-induced diabetic model, similar to glibenclamide (standard), from 208.33 mg/dl to 106.38 mg/dl at 200 mg/kg CEPS and from 209.82 mg/dl to 111.65 mg/dl at 400 mg/kg CEPS. These findings were comparable with 0.5 mg/kg of glibenclamide indicating a substantial decrease from 205.55 mg/dl on 7th day to 84.88 mg/dl. The Pastinaca sativa methanolic extract possesses strong antidiabetic activity in vivo. Besides, the extract has also been shown to have a significant inhibitory activity of α-amylase and α-glucosidase, which might lead to its anti-hyperglycemic function when used in diabetic patients.

Hydroxychloroquine (HCQ) and its derivatives have recently gained tremendous attention as a probable medicinal agent in the COVID-19 outbreak caused by SARS-CoV-2. An efficient agent to act directly in inhibiting the SARS-CoV-2 replication is yet to be achieved. Thus, the goal is to investigate the dynamic nature of HCQ derivatives against SARS-CoV-2 main protease and spike proteins. Molecular docking studies were also performed to understand their binding affinity in silico methods using the vital protein domains and enzymes involved in replicating and multiplying SARS-CoV-2, which were the main protease and spike protein. Molecular Dynamic simulations integrated with MM-PBSA calculations have identified In silico potential inhibitors ZINC05135012 and ZINC59378113 against the main protease with −185.171 ± 16.388, −130.759 ± 15.741 kJ/mol respectively, ZINC16638693 and ZINC59378113 against spike protein −141.425 ± 22.447, −129.149 ± 11.449 kJ/mol. Identified Hit molecules had demonstrated Drug Likeliness features, PASS values and ADMET predictions with no violations. Communicated by Ramaswamy H. Sarma HighlightsDrug repurposing and drug-related compounds have become an emerging tactic to fight COVID-19.Hydroxychloroquine analogues were retrieved from the ZINC database through ZINCPharmer and used for docking with Main protease and Spike proteins of SARS-CoV-2.However, the binding energies of the compounds ZINC05135012 and ZINC59378113 were found lower compared to Hydroxychloroquine.Both the hit molecules have cleared drug-likeness features and AMDET predictions with no violations Drug repurposing and drug-related compounds have become an emerging tactic to fight COVID-19. Hydroxychloroquine analogues were retrieved from the ZINC database through ZINCPharmer and used for docking with Main protease and Spike proteins of SARS-CoV-2. However, the binding energies of the compounds ZINC05135012 and ZINC59378113 were found lower compared to Hydroxychloroquine. Both the hit molecules have cleared drug-likeness features and AMDET predictions with no violations

Cinnamon has been utilized to remedy a lot of afflictions of humans. Literary works illustrate that it possesses numerous biological activities. Our research study is intended to recognize the phyto-derived antiviral substances from Cinnamon against COVID-19 main protease enzyme and to understand the in silico molecular basis of its activity. In the present study, 48 isolates compounds from Cinnamon retrieved from the PubMed database, are subjected to docking analysis. Docking study was performed using Autodock vina and PyRx software. Afterwards, admetSAR, as well as DruLiTo servers, were used to investigate drug-likeness prophecy. Our study shows that the nine phytochemicals of Cinnamon are very likely against the main protease enzyme of COVID-19. Further MD simulations could identify Tenufolin (TEN) and Pavetannin C1 (PAV) as hit compounds. Utilizing contemporary strategies, these phyto-compounds from a natural origin might establish a reliable medication or support lead identification. Identified hit compounds can be further taken for in vitro and in vivo studies to examine their effectiveness versus COVID-19., Graphical Abstract Communicated by Ramaswamy H. Sarma