Cationic host defence peptides (CHDP), also known as antimicrobial peptides, are naturally occurring peptides that can combat infections through their direct microbicidal properties and/or by influencing the host's immune responses. The unique ability of CHDP to control infections as well as resolve harmful inflammation has generated interest in harnessing the properties of these peptides to develop new therapies for infectious diseases, chronic inflammatory disorders and wound healing. Various strategies have been used to design synthetic optimized peptides, with negligible toxicity. Here, we focus on the progress made in understanding the scope of functions of CHDP and the emerging potential clinical applications of CHDP-based therapies.

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Antimicrobial host defence peptides: functions and clinical potential

Milk bioactive peptide database: A comprehensive database of milk protein-derived bioactive peptides and novel visualization

Antibiotics are essential drugs used to treat pathogenic bacteria, but their prolonged use contributes to the development and spread of drug-resistant microorganisms. Antibiotic resistance is a serious challenge and has led to the need for new alternative molecules less prone to bacterial resistance. Antimicrobial peptides (AMPs) have aroused great interest as potential next-generation antibiotics, since they are bioactive small proteins, naturally produced by all living organisms, and representing the first line of defense against fungi, viruses and bacteria. AMPs are commonly classified according to their sources, which are represented by microorganisms, plants and animals, as well as to their secondary structure, their biosynthesis and their mechanism of action. They find application in different fields such as agriculture, food industry and medicine, on which we focused our attention in this review. Particularly, we examined AMP potential applicability in wound healing, skin infections and metabolic syndrome, considering their ability to act as potential Angiotensin-Converting Enzyme I and pancreatic lipase inhibitory peptides as well as antioxidant peptides. Moreover, we argued about the pharmacokinetic and pharmacodynamic approaches to develop new antibiotics, the drug development strategies and the formulation approaches which need to be taken into account in developing clinically suitable AMP applications.

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Antimicrobial Peptides: A New Hope in Biomedical and Pharmaceutical Fields

Bioprotective mechanisms of lactic acid bacteria against fungal spoilage of food.

Fungi have been used since ancient times in food and beverage-making processes and, more recently, have been harnessed for the production of antibiotics and in processes of relevance to the bioeconomy. Moreover, they are starting to gain attention as a key component of the human microbiome. However, fungi are also responsible for human infections. The incidence of community-acquired and nosocomial fungal infections has increased considerably in recent decades. Antibiotic resistance development, the increasing number of immunodeficiency- and/or immunosuppression-related diseases and limited therapeutic options available are triggering the search for novel alternatives. These new antifungals should be less toxic for the host, with targeted or broader antimicrobial spectra (for diseases of known and unknown etiology, respectively) and modes of actions that limit the potential for the emergence of resistance among pathogenic fungi. Given these criteria, antimicrobial peptides with antifungal properties, i.e., antifungal peptides (AFPs), have emerged as powerful candidates due to their efficacy and high selectivity. In this review, we provide an overview of the bioactivity and classification of AFPs (natural and synthetic) as well as their mode of action and advantages over current antifungal drugs. Additionally, natural, heterologous and synthetic production of AFPs with a view to greater levels of exploitation is discussed. Finally, we evaluate the current and potential applications of these peptides, along with the future challenges relating to antifungal treatments.

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Antifungal Peptides as Therapeutic Agents.

Antimicrobial peptides (AMPs) represent a vast array of molecules produced by virtually all living organisms as natural barriers against infection. Among AMP sources, an interesting class regards the food-derived bioactive agents. The whey protein lactoferrin (Lf) is an iron-binding glycoprotein that plays a significant role in the innate immune system, and is considered as an important host defense molecule. In search for novel antimicrobial agents, Lf offers a new source with potential pharmaceutical applications. The Lf-derived peptides Lf(1-11), lactoferricin (Lfcin) and lactoferrampin exhibit interesting and more potent antimicrobial actions than intact protein. Particularly, Lfcin has demonstrated strong antibacterial, anti-fungal and antiparasitic activity with promising applications both in human and veterinary diseases (from ocular infections to osteo-articular, gastrointestinal and dermatological diseases).

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Antimicrobial Activity of Lactoferrin-Related Peptides and Applications in Human and Veterinary Medicine.

Leishmaniasis is a vector-borne zoonotic disease caused by protozoan parasites of the genus Leishmania, which are responsible for numerous clinical manifestations, such as cutaneous, visceral, and mucocutaneous leishmaniasis, depending on the site of infection for particular species. These complexities threaten 350 million people in 98 countries worldwide. Amastigotes living within macrophage phagolysosomes are the principal target of antileishmanial treatment, but these are not an easy target as drugs must overcome major structural barriers. Furthermore, limitations on current therapy are related to efficacy, toxicity, and cost, as well as the length of treatment, which can increase parasitic resistance. Nanotechnology has emerged as an attractive alternative as conventional drugs delivered by nanosized carriers have improved bioavailability and reduced toxicity, together with other characteristics that help to relieve the burden of this disease. The significance of using colloidal carriers loaded with active agents derives from the physiological uptake route of intravenous administered nanosystems (the phagocyte system). Nanosystems are thus able to promote a high drug concentration in intracellular mononuclear phagocyte system (MPS)-infected cells. Moreover, the versatility of nanometric drug delivery systems for the deliberate transport of a range of molecules plays a pivotal role in the design of therapeutic strategies against leishmaniasis. This review discusses studies on nanocarriers that have greatly contributed to improving the efficacy of antileishmaniasis drugs, presenting a critical review and some suggestions for improving drug delivery.

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Nanostructured delivery systems with improved leishmanicidal activity: a critical review.

Preparation and characterization of cyclodextrin nanosponges for organic toxic molecule removal.

Background: Liver pathology in cats represents a frequent clinical condition occurring in animals of any age. Dietary supplementation with hepatoprotective and antioxidant products could represent a beneficial strategy to prevent and treat these disorders. We evaluated the tolerability and efficacy of long-term treatment with a multi-component, dietary supplement containing functional natural ingredients with recognized hepatoprotective properties in cats suffering from liver diseases Methods: 20 European domestic cats of either gender, 10 with hepatic lipidosis and 10 with cholangitis received for 180 consecutive days a multi-component formulation based on the silibinin-phosphatidylcholine complex as paste or tablet. Clinical assessment and blood and urine parameters were evaluated at T0 (inclusion time) and after 7, 28, 60, 90 and 180 days from the initiation of the study. Results: The oral supplementation with the silibinin-phosphatidylcholine complex significantly reduced the activity of liver enzymes in serum (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ -glutamyl transferase) and the content of total bilirubin, albumin, preand postbile acids, in cats with hepatic lipidosis or cholangitis, normalizing their liver function parameters. Moreover, following the supplementation, the appetite was restored in all cats and the frequent episodes of diarrhea and vomit reported at inclusion almost disappeared. Discussion: Dietary supplementation with the silibinin-phosphatidylcholine complex containing functional natural ingredients with recognized hepatoprotective and antioxidant actions might represent an effective strategy to improve the conditions of liver dysfunction, such as hepatitis lipidosis and cholangitis, in cats.

Leonardo Giraudo

Papers

Antimicrobial Activity of Lactoferrin-Related Peptides and Applications in Human and Veterinary Medicine.

Nanostructured delivery systems with improved leishmanicidal activity: a critical review.

Preparation and characterization of cyclodextrin nanosponges for organic toxic molecule removal.

Effect of an oral dietary supplementation by a formulation based on silibinin-phosphatidylcholine complex in cats with liver diseases