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Parasitic nematodes infect almost all forms of life. In the human context, parasites are one of the major causative factors for physical and intellectual growth retardation in the developing world. In the agricultural setting, parasites have a great economic impact through a reduction in livestock performance or control cost. The main method of controlling these devastating conditions is the use of anthelmintic drugs. Unfortunately, there are only a few anthelmintic drug classes available in the market and significant resistance has developed in most of the parasitic species of livestock. Therefore, development of new anthelmintics with different modes of action is critical for sustainable parasitic control in the future. The drug development pipeline is broadly limited to two types of molecules, namely synthetic compounds and natural plant products. Compared to synthetic compounds, natural products are highly diverse, and many have historically proven valuable in folk medicine to treat various gastrointestinal ailments. This review focus on the use of traditional knowledge-based plant extracts in the development of new therapeutic leads, the approaches used as screening techniques, and common bottlenecks and opportunities in plant-based anthelmintic drug discovery.

Antimicrobial peptides (AMPs) have been established over millennia as powerful components of the innate immune system of many organisms. Due to their broad spectrum of activity and the development of host resistance against them being unlikely, AMPs are strong candidates for controlling drug-resistant pathogenic microbial pathogens. AMPs cause cell death through several independent or cooperative mechanisms involving membrane lysis, non-lytic activity, and/or intracellular mechanisms. Biochemical determinants such as peptide length, primary sequence, charge, secondary structure, hydrophobicity, amphipathicity and host cell membrane composition together influence the biological activities of peptides. A number of biophysical techniques have been used in recent years to study the mechanisms of action of AMPs. This work appraises the molecular parameters that determine the biocidal activity of AMPs and overviews their mechanisms of actions and the diverse biochemical, biophysical and microscopy techniques utilised to elucidate these.

Two new antimicrobial agents, neryl ferulate (1) and neryl p-coumarate (2), were identified using bioassay-guided isolation from the leaves of Eremophila longifolia, which is a medicinal plant used by some Australian Aboriginal communities. Although gradual autoxidation of the nerol subunit hindered the initial attempts to purify and characterize 1 and 2, it was found that the autoxidation could be stopped through storage under argon at -20 °C. Biological evaluation showed that neryl ferulate (1) had moderate activity against various Gram-positive bacteria, while neryl p-coumarate (2) was active only against Enterococcus faecium.

Drug-resistant microorganisms ('superbugs') present a serious challenge to the success of antimicrobial treatments. Subsequently, there is a crucial need for novel bio-control agents. Many antimicrobial peptides (AMPs) show a broad-spectrum activity against bacteria, fungi or viruses and are strong candidates to complement or substitute current antimicrobial agents. Some AMPs are also effective against protozoa or cancer cells. The tryptophan (Trp)-rich peptides (TRPs) are a subset of AMPs that display potent antimicrobial activity, credited to the unique biochemical properties of tryptophan that allow it to insert into biological membranes. Further, many Trp-rich AMPs cross bacterial membranes without compromising their integrity and act intracellularly, suggesting interactions with nucleic acids and enzymes. In this work, we overview some archetypal TRPs derived from natural sources, i.e., indolicidin, tritrpticin and lactoferricin, summarising their biochemical properties, structures, antimicrobial activities, mechanistic studies and potential applications.

The puroindoline proteins (PINA and PINB) of wheat display lipid-binding properties which affect the grain texture, a critical parameter for wheat quality. Interestingly, the same proteins also display antibacterial and antifungal properties, attributed mainly to their Tryptophan-rich domain (TRD). Synthetic peptides based on this domain also display selectivity towards bacterial and fungal cells and do not cause haemolysis of mammalian cells. However, the mechanisms of these activities are unclear, thus limiting our understanding of the in vivo roles of PINs and development of novel applications. This study investigated the mechanisms of antimicrobial activities of synthetic peptides based on the TRD of the PINA and PINB proteins. Calcein dye leakage tests and transmission electron microscopy showed that the peptides PuroA, Pina-M and Pina-W→F selectively permeabilised the large unilamellar vesicles (LUVs) made with negatively charged phospholipids mimicking bacterial membranes, but were ineffective against LUVs made with zwitterionic phospholipids mimicking eukaryotic membranes. Propidium iodide fluorescence tests of yeast (Saccharomyces cerevisiae) cells showed the peptides were able to cause loss of membrane integrity, PuroA and Pina-M being more efficient. Scanning electron micrographs of PINA-based peptide treated yeast cells showed the formation of pits or pores in cell membranes and release of cellular contents. Gel retardation assays indicated the peptides were able to bind to DNA in vitro, and the induction of filamental growth of E. coli cells indicated in vivo inhibition of DNA synthesis. Together, the results strongly suggest that the PIN-based peptides exert their antimicrobial effects by pore formation in the cell membrane, likely by a carpet-like mechanism, followed by intracellular mechanisms of activity.

Abstract: Experimental assays were carried out to validate traditional claims about medicinal plants collected by the Traditional Knowledge Documentation Program at the Sarawak Biodiversity Centre on the island of Borneo. The majority of the medicinal plants are utilised as traditional therapies for various diseases, including diarrhoea, food poisoning, vaginomycosis, sexually transmitted infections (gonorrhoea) and furunculosis. Six medicinal plants used as indigenous herbal medicines were individually screened for antimicrobial and antifungal effects using their crude extracts and were found to inhibit a broad range of pathogenic microorganisms. Plant extracts derived from Fibraurea tinctoria, Polyalthia hookeriana, Pyrenaria sp., Baccaurea lanceolata, Goniothalamus tapisoides and Goniothalamus velutinus were demonstrated to have the highest antimicrobial activities. Pyrenaria sp. showed significant antifungal activity against Candida albicans with minimum inhibitory and minimum fungicidal concentrations of 25μg/mL and 50μg/mL, respectively. The evidence in this study has highlighted the effectiveness of using the traditional knowledge approach to screen for antimicrobial and antifungal activity in plants to evaluate their potential as herbal remedies for human and animal protection against pathogens. [Copyright &y& Elsevier]