Plant-based Natural Products as inhibitors for Efflux Pumps to Reverse Multidrug Resistance in Staphylococcus aureus: A Mini Review.

Wounds provide a favourable site for microbial infection. Wound infection makes the healing more complex and does not proceed in an orchestrated manner leading to the chronic wound. Clinically infected wounds require proper antimicrobial therapy. Broad-spectrum antibiotics are usually prescribed first before going to targeted therapy. The current conventional mode of therapy mainly depends on the use of antibiotics topically or systemically. Repeated and prolonged use of antibiotics, however, leads to multidrug resistance. Staphylococcus aureus is the most common multidrugresistant microorganism found in wounds. It effectively colonizes the wound and produces many toxins, thereby reducing the host immune response and causing recurrent infection, thus making the wound more complex. The overexpression of efflux pumps is one of the major reasons for the emergence of multidrug resistance. Inhibition of efflux pumps is, therefore, a potential strategy to reverse this resistance. The effective therapy to overcome this antibiotic resistance is to use combination therapy, namely the combination of an inhibitor, and a non-antibiotic compound with an antibiotic for their dual function. Many synthetic efflux pump inhibitors to treat wound infections are still under clinical trials. In this connection, several investigations have been carried out on plant-based natural products as multidrug resistance-modifying agents as they are believed to be safe, inexpensive and suitable for chronic wound infections.

1-Tetracosanol isolated from the leaves of Eupatorium glandulosum, accelerates wound healing by expressing inflammatory cytokines and matrix metalloproteinase.

ETHNOPHARMACOLOGICAL RELEVANCE: The leave paste of the plant, Eupatorium glandulosum H. B & K, has been traditionally used to treat cuts and wounds by the tribal community of the Nilgiris district of Tamilnadu, India. AIM OF THE STUDY: The present study was carried out to investigate the wound healing potential of this plant extract and the compound, 1-Tetracosanol, isolated from the ethyl acetate fraction. MATERIALS AND METHODS: An in vitro study was designed to compare the viability, migration and apoptosis of the fresh methanolic extract fractions and 1-Tetracosanol using mouse fibroblast NIH3T3 cell lines and human keratinocytes HaCaT cell lines, respectively. 1-Tetracosanol was evaluated for its viability, migration, qPCR analysis, in silico, in vitro and in vivo. RESULTS: 1-Tetracosanol at the concentration of 800, 1600, 3200 µM has significant wound closure of 99% at 24 h. The compound when screened in silico against various wound healing markers, TNF-α, IL-12, IL-18, GM-CSF and MMP-9, revealed high binding energy of -5, 4.9 and -6.4 kcal/mol for TNF-α, IL-18 and MMP-9, respectively. Gene expression and the release of cytokines increased at an early stage of the wound repair. 1-Tetracosanol, at 2% gel showed 97.35 ± 2.06% wound closure at 21st day. CONCLUSION: 1-Tetracosanol is a good lead for drug development targeted towards wound healing activity and work in this direction is in progress.

Repurposing of FDA Approved Drugs and Neuropep peptides as Anticancer Agents Against ErbB1 and ErbB2.

ErbB1 and ErbB2 are the most important biological targets in cancer drug discovery and development of dual inhibitors for the cancer therapy. FDA approved drugs and Neuropep peptides were used to fit into the ATP binding site of the tyrosine kinases; ErbB1 and ErbB2 proteins. Cytoscape, iGEMDOCK, HPEPDOCK and DataWarrior softwares were used to study the role of these agents as anticancer drugs. Eleven FDA approved drugs and eleven Neuropep peptides showed the strongest 2D interactions and significant binding energy with the proteins. Invitro MTT anticancer assay revealed that, the test compounds, peptide YSFGL and doxorubicin showed significant IC50 value (µM) of 26.417±0.660 and 7.675±0.278 respectively which are compared with the lapatinib standard IC50 value (µM) of 2.380±0.357 against A549 cells and IC50 value (µM) of 39.047±0.770 and 8.313±0.435 respectively which are compared with the lapatinib standard IC50 value (µM) of 3.026±0.180 against MDA-MB-231 cells.

Plant-based Natural Products for Wound Healing: A Critical Review.

Wound healing is an intricate process consisting of four overlapping phases, namely hemostasis, inflammation, proliferation, and remodelling. Effective treatment of wounds depends upon the interaction of appropriate cell types, cell surface receptors, and the extracellular matrix with the therapeutic agents. Several approaches currently used for treating wounds, such as advanced wound dressing, growth factor therapy, stem cell therapy, and gene therapy, are not very effective and lead to impaired healing. Further, repeated use of antibiotics to treat open wounds leads to multi- drug resistance. Today there is considerable interest in plant-based drugs as they are believed to be safe, inexpensive, and more suitable for chronic wounds. For example, a large number of plant- based extracts and their bioactive compounds have been investigated for wound healing. In recent years the structural and mechanistic diversity of natural products have become central players in the search for newer therapeutic agents. In the present review, a thorough critical survey of the traditionally used plant-based drugs used worldwide for wound healing with special reference to the natural products/bioactive compounds isolated and screened is presented. It is hoped that this review will attract the attention of the research community involved in newer drug design and development for wound healing.