Muhammad Mohtasheemul Hasan

Introduction: Study was taken with an objective to investigate the inhibitory effect of Phaseolus lunatus seeds extract on three enzymes (α-amylase, maltase and glucoamylase) which are involved in diabetes. The disadvantages related with the use of synthetic drugs make it necessary to search for alternative drugs from medicinal plants. One therapeutic approach for the treatment of postprandial hyperglycaemia is to decrease the plasma glucose level which can be attained by lowering the starch hydrolysis by digestive enzymes such as α-amylase, maltase and glucoamylase. The use of synthetic antidiabetic agents caused gastrointestinal side effects. Methods: Hence, the research was aimed to evaluate the potential of Phaseolus lunatus seeds extract to inhibit α-amylase, maltase and glucoamylase as a possible mechanism of hypoglycemia caused by this plant with less side effects. Phaseolus lunatus, also known as Lima bean, is native to Tropical America and are grown throughout the world. Lima bean has been prescribed traditionally to treat different diseases including diabetes. Result: The results of the present study showed that Phaseolus lunatus seeds extract have exerted both time and concentration dependent significant inhibitory effect on these digestive enzymes which might be due to cumulative effect of phytoconstituents present in the plant extract. Conclusion: Therefore, it can be said that the part of mechanisms by which Phaseolus lunatus exhibited its antidiabetic activity might be through the inhibition of these digestive enzyme.

Prevalence of oral infections in diabetic patients is a health challenge due to persistent hyperglycemia. However, despite great concerns, limited treatment options are available. We therefore aimed to develop nanoemulsion gel (NEG) for oral bacterial infections based on essential oils. Clove and cinnamon essential oils based nanoemulgel were prepared and characterized. Various physicochemical parameters of optimized formulation including viscosity (65311 mPa·S), spreadability (36 g·cm/s), and mucoadhesive strength 42.87 N/cm²) were within prescribed limits. The drug contents of the NEG were 94.38 ± 1.12% (cinnamaldehyde) and 92.96 ± 2.08% (clove oil). A significant concentration of clove (73.9%) and cinnamon essential oil (71.2 %) was released from a polymer matrix of the NEG till 24 h. The ex vivo goat buccal mucosa permeation profile revealed a significant (52.7–54.2%) permeation of major constituents which occurred after 24 h. When subjected to antimicrobial testing, significant inhibition was observed for several clinical strains, namely Staphylococcus aureus (19 mm), Staphylococcus epidermidis (19 mm), and Pseudomonas aeruginosa (4 mm), as well as against Bacillus chungangensis (2 mm), whereas no inhibition was detected for Bacillus paramycoides and Paenibacillus dendritiformis when NEG was utilized. Likewise promising antifungal (Candida albicans) and antiquorum sensing activities were observed. It was therefore concluded that cinnamon and clove oil-based NEG formulation presented significant antibacterial-, antifungal, and antiquorum sensing activities.

Euphorbia nivulia-Ham (EN) is a neglected medicinal plant traditionally used for a number of pathologies, but it has not been explored scientifically. In the current study, its various fractions were assessed for their phenolic and flavonoid content, radical scavenging, as well as its enzyme inhibitory potential. The hydro-alcoholic crude extract (ENCr) was subjected to a fractionation scheme to obtain different fractions, namely n-hexane (ENHF), chloroform (ENCF), n-butanol (ENBF), and aqueous fraction (ENAF). The obtained results revealed that the highest phenolic and flavonoid content, maximum radical scavenging potential (91 ± 0.55%), urease inhibition (54.36 ± 1.47%), and α-glucosidase inhibition (97.84 ± 1.87%) were exhibited by ENCr, while the ENBF fraction exhibited the highest acetylcholinestrase inhibition (57.32 ± 0.43%). Contrary to these, hydro-alcoholic crude as well as the other fractions showed no significant butyrylcholinestrases (BChE) and carbonic anhydrase inhibition activity. Conclusively, it was found that EN possesses a significant radical scavenging and enzyme inhibitory potential. Thus, the study may be regarded a step forward towards evidence-based phyto-medicine.

In this research, structure of SARS-CoV-2 spike glycoprotein S1 and S2 along with TMPRSS2, TMPRSS4, TMPRSS11A, TMPRSS11D and TMPRSS11E serine protease (which activates S1 and S2) are used for docking with repurposed inhibitor drug molecules. We searched for a universally active drug molecule which binds with glycoproteins and serine protease with binding energy above a pre-set threshold value, thus single handedly inhibits the virus glycoprotein interaction with ACE-II receptor on human cell preventing the virus RNA transfer to human cell. Through data analysis performed on binding energies of the selected repurposed inhibitors, we found out five molecules to have high binding energies on both spike glycoproteins and serine protease, while showing less variance in their binding energies. Among these five, Edoxaban is an FDA approved commercially available drug molecule. Hence, high binding molecular inhibitors for spike glycoprotein and serine protease for treatment of SARS-CoV-2 were identified.

In this research we used the structure of SARS-CoV-2 related, recently mapped, atomic structure of nsp10/16 proteins for docking with some known drug molecular structures at pH 7 and 5. Chosen molecules were azo -N=N- and -COOH derivatives. It was revealed that the molecules showed good binding energy with nsp10/16 protein at both pH. These molecules can act as protein-nucleic acid interface (PNAI) inhibitor drug molecules. Such molecules can be used in combination with polymerase and protease inhibitors for treatment of SARS-CoV-2.

In this research we used the structure of SARS-CoV-2 main protease (Mpro) for docking with Anti-HIV protease inhibitor drug molecules within pH 4-8. By carrying out the variance analysis of binding energies at pH 4-8, it was revealed that the binding energy and mode of interaction of the potential ligands with SARS-CoV-2 Mpro, was dependent on variation of pH. We found out that two of the selected protease inhibitors have differential binding characteristics with changing pH hence their binding energies and mode of interaction depends upon intracellular pH. This differential binding behavior can lead to development of pH selective potent drug molecules for binding with viral protease at lowered intracellular pH of virus infected cell.

The objective was to use caffeine and Soluplus® to improve the dissolution rate and to maintain a concentration of BCS Class II rosuvastatin calcium that exceeds its solubility. Caffeine and Soluplus® together substantially improved the dissolution rate and the extent of rosuvastatin release. Formulations for direct compression tablets included Formulation F1, a control with drug but with neither caffeine nor Soluplus® present; F2 with drug-caffeine complex; F3 with drug and Soluplus® and F4 with drug-caffeine complex and Soluplus®. Each formulation blend provided satisfactory flow properties. Tablets were comparable in mass, hardness and friability. A marked decrease in disintegration time occurred when the hydrotropic or micellar agent was included in the formulation. Assay (98-100%) and content uniformity (99-100%) results met requirements. Release studies in pH 1.2, 6.6, and 6.8 buffers revealed the superiority of F4. At 45 min sampling time, F3 and F4 tablets each provided a cumulative drug release greater than 70% in each medium. F2 tablets exhibited compliance to official standards in pH 6.6 and 6.8 buffers but not in pH 1.2 buffer, whereas tablets based on F1 failed in each medium. Two-factor ANOVA of the release data revealed a statistical difference across the four formulations in each release medium. Pairwise comparison of release profiles demonstrated that, of the four formulations, F4 provided the most effectively enhanced dissolution rate, improvement to the extent of drug release and support of a concentration higher than the solubility of rosuvastatin calcium.