Screening of potential phytomolecules against MurG as drug target in nosocomial pathogen Pseudomonas aeruginosa: perceptions from computational campaign.

The nosocomial infection outbreak caused by Pseudomonas aeruginosa remains a public health concern. Multi-drug resistant (MDR) strains of P. aeruginosa are rapidly spreading leading to a huge mortality rate because of the unavailability of promising antimicrobials. MurG glycotransferase [UDP-N-acetylglucosamine-N-acetylmuramyl (pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase] is located at the plasma membrane and plays a key role in murein (peptidoglycan) biosynthesis in bacteria. Since MurG is required for bacterial cell wall synthesis and is non-homologous to Homo sapiens; it can be a potential target for the antagonist to treat P. aeruginosa infection. The discovery of high-resolution crystal structure of P. aeruginosa MurG offers an opportunity for the computational identification of its prospective inhibitors. Therefore, in the present study, the crystal structure of MurG (PDB ID: 3S2U) from P. aeruginosa was selected, and computational docking analyses were performed to search for functional inhibitors of MurG. IMPPAT (Indian medicinal plants, phytochemicals and therapeutic) phytomolecule database was screened by computational methods with MurG catalytic site. Docking results identified Theobromine (-8.881 kcal/mol), demethoxycurcumin (-8.850 kcal/mol), 2-alpha-hydroxycostic acid (-8.791 kcal/mol), aurantiamide (-8.779 kcal/mol) and petasiphenol (-8.685 kcal/mol) as a potential inhibitor of the MurG activity. Further, theobromine and demethoxycurcumin were subjected to MDS (molecular dynamics simulation) and free energy (MM/GBSA) analysis to comprehend the physiological state and structural stability of MurG-phytomolecules complexes. The outcomes suggested that these two phytomolecules could act as most favorable natural hit compounds for impeding the enzymatic action of MurG in P. aeruginosa, and thus it needs further validation by both in vitro and in vivo analysis. HIGHLIGHTSThe top phytomolecules such as theobromine, demethoxycurcumin, 2-alpha-hydroxycostic acid, aurantiamide and petasiphenol displayed promising binding with MurG catalytic domain.MurG complexed with theobromine and demethoxycurcumin showed the best interaction and stable by MD simulation at 100 ns.The outcome of MurG binding phytomolecules has expanded the possibility of hit phytomolecules validation.Communicated by Ramaswamy H. Sarma.

Nigella sativa and its nano-mediated approach toward management of neurodegenerative disorders: A review.

Nigella sativa L., also known as black seed or black cumin, is a plant that has been used for centuries. In the past, this flowering plant was used as a food preservative and medicinal herb. A vital component of Nigella sativa, thymoquinone (TQ), plays a significant therapeutic role in the management of most diseases, including cancer, diabetes mellitus, hypertension, inflammation, gastrointestinal disorders, and neurodegenerative disorders. Neurodegenerative disorders are primarily caused by neurotransmitter hypoactivity, particularly insufficient serotonin activity. It has been discovered that many medicinal herbs and their active compounds have therapeutic value. Black cumin seeds have been used to heal ailments and its history traces back to ancient times such as ancient Babylonia. They can be used applied to alleviate edema, hair loss, and bruising, and consumd to treat stomach issues. It is one of the most feasible and effective medicinal plants. The use of nanoformulations based on Nigella sativa and TQ to treat neurodegenerative diseases (NDs) has yielded promising outcomes. Customized administration of nanoparticle (NP) systems and nanomedicine are two of the many options for drug delivery to the central nervous system (CNS) that are attracting increasing interest. Delivering a therapeutic and diagnostic substance to a particular location is the core target of NPs. Because of their distinct cell uptake and trafficking mechanisms, NPs can reduce the amount that accumulates in undesirable organs. The focus of the current review is on recent studies on the various neuroprotective properties of Nigella sativa as well as nanoformulations for NDs and the brain's uptake of NPs. The review summarizes the In vivo, In vitro, and In silico studies on the protective effects of black cumin against neurodegenerative disorders.

In vitro callus induction and estimation of plumbagin content from Plumbago auriculata Lam.

The medicinal plant Plumbago contains a very potent secondary metabolite, plumbagin having many therapeutic properties. Callus culture was induced using explants, leaf, stem and shoot apex, from P. auriculata. Murashige and Skoog media fortified with various growth hormones like NAA, IAA, IBA and 2, 4-D individually and in various combinations were checked for callus induction. Among the growth hormones used, 1 mg/L 2, 4-D showed best callusing. The hormonal combinations of 1 mg/L IAA and 1.5 mg/L NAA in the media exhibited best callus induction using stem internode as an explant. Plumbagin content from root, stem, leaf and callus was analyzed by using thin layer chromatographic technique. The callus derived from stem showed comparable plumbagin content to the in vivo plant parts. Quantitative spectrophotometric analysis of plumbagin from plant samples and callus indicated that plumbagin content was maximum in roots which was followed by callus, stem and leaf samples respectively. Generation of in vitro sources for p!umbagin, for therapeutic applications will serve as a continuous supply and will contribute to preserve the natural plant recourses.