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Host defence peptides (HDPs) are integral components of innate immunity across all living organisms. These peptides can exert direct antibacterial effects, targeting planktonic cells (referred to as antimicrobial peptides), and exhibit antibiofilm (referred to as antibiofilm peptides), antiviral, antifungal and host-directed immunomodulatory activities. In this Review, we discuss how the complex functional attributes of HDPs provide many opportunities for the development of antimicrobial therapeutics, focusing particularly on their emerging antibiofilm properties. The mechanisms of action of antibiofilm peptides are compared and contrasted with those of antimicrobial peptides. Furthermore, obstacles for the practical translation of candidate peptides into therapeutics and the potential solutions are discussed. Critically, HDPs have the value-added assets of complex functional attributes, particularly antibiofilm and anti-inflammatory activities and their synergy with conventional antibiotics.In this Review, Hancock, Alford and Haney discuss how the complex functional attributes of host defence peptides provide many opportunities for the development of antimicrobial therapeutics, focusing on their emerging antibiofilm properties.

Sesquiterpene lactones (SL), characterized by their high prevalence in the Asteraceae family, are one of the major groups of secondary metabolites found in plants. Researchers from distinct research fields, including pharmacology, medicine, and agriculture, are interested in their biological potential. With new SL discovered in the last years, new biological activities have been tested, different action mechanisms (synergistic and/or antagonistic effects), as well as molecular structure–activity relationships described. The review identifies the main sesquiterpene lactones with interconnections between immune responses and anti-inflammatory actions, within different cellular models as well in in vivo studies. Bioaccessibility and bioavailability, as well as molecular structure–activity relationships are addressed. Additionally, plant metabolic engineering, and the impact of sesquiterpene lactone extraction methodologies are presented, with the perspective of biological activity enhancement. Sesquiterpene lactones derivatives are also addressed. This review summarizes the current knowledge regarding the therapeutic potential of sesquiterpene lactones within immune and inflammatory activities, highlighting trends and opportunities for their pharmaceutical/clinical use.

Food components have long been recognized to play a fundamental role in the growth and development of the human body, conferring protective functionalities against foreign matter that can be severe public health problems. Micronutrients such as vitamins and minerals are essential to the human body, and individuals must meet their daily requirements through dietary sources. Micronutrients act as immunomodulators and protect the host immune response, thus preventing immune evasion by pathogenic organisms. Several experimental investigations have been undertaken to appraise the immunomodulatory functions of vitamins and minerals. Based on these experimental findings, this review describes the immune-boosting functionalities of micronutrients and the mechanisms of action through which these functions are mediated. Deficiencies of vitamins and minerals in plasma concentrations can lead to a reduction in the performance of the immune system functioning, representing a key contributor to unfavorable immunological states. This review provides a descriptive overview of the characteristics of the immune system and the utilization of micronutrients (vitamins and minerals) in preventative strategies designed to reduce morbidity and mortality among patients suffering from immune invasions or autoimmune disorders.

Acne is a chronic inflammatory skin disease with a recurring nature that seriously impacts patients’ quality of life. Currently, antibiotic resistance has made it less effective in treating acne. However, Paris polyphylla (P. polyphylla) is a valuable medicinal plant with a wide range of chemical components. Of these, P. polyphylla saponins modulate the effects in vivo and in vitro through antibacterial, anti-inflammatory, immunomodulatory, and antioxidant effects. Acne is primarily associated with inflammatory reactions, abnormal sebum function, micro-ecological disorders, hair follicle hyperkeratosis, and, in some patients, immune function. Therefore, the role of P. polyphylla saponins and their values in treating acne is worthy of investigation. Overall, this review first describes the distribution and characteristics of P. polyphylla and the pathogenesis of acne. Then, the potential mechanisms of P. polyphylla saponins in treating acne are listed in detail (reduction in the inflammatory response, antibacterial action, modulation of immune response and antioxidant effects, etc.). In addition, a brief description of the chemical composition of P. polyphylla saponins and its available extraction methods are described. We hope this review can serve as a quick and detailed reference for future studies on their potential acne treatment.

The review presents the latest data on the role of selenium-containing agents in the regulation of diseases of the immune system. We mainly considered the contributions of selenium-containing compounds such as sodium selenite, methylseleninic acid, selenomethionine, and methylselenocysteine, as well as selenoproteins and selenium nanoparticles in the regulation of defense mechanisms against various viral infections, including coronavirus infection (COVID-19). A complete description of the available data for each of the above selenium compounds and the mechanisms underlying the regulation of immune processes with the active participation of these selenium agents, as well as their therapeutic and pharmacological potential, is presented. The main purpose of this review is to systematize the available information, supplemented by data obtained in our laboratory, on the important role of selenium compounds in all of these processes. In addition, the presented information makes it possible to understand the key differences in the mechanisms of action of these compounds, depending on their chemical and physical properties, which is important for obtaining a holistic picture and prospects for creating drugs based on them.

The use of deer antlers dates back thousands of years in Chinese history. Deer antlers have antitumor, anti-inflammatory, and immunomodulatory properties and can be used in treating neurological diseases. However, only a few studies have reported the immunomodulatory mechanism of deer antler active compounds. Using network pharmacology, molecular docking, and molecular dynamics simulation techniques, we analyzed the underlying mechanism by which deer antlers regulate the immune response. We identified 4 substances and 130 core targets that may play immunomodulatory roles, and the beneficial and non-beneficial effects in the process of immune regulation were analyzed. The targets were enriched in pathways related to cancer, human cytomegalovirus infection, the PI3K-Akt signaling pathway, human T cell leukemia virus 1 infection, and lipids and atherosclerosis. Molecular docking showed that AKT1, MAPK3, and SRC have good binding activity with 17 beta estradiol and estrone. Additionally, the molecular dynamics simulation of the molecular docking result using GROMACS software (version: 2021.2) was performed and we found that the AKT1–estrone complex, 17 beta estradiol–AKT1 complex, estrone–MAPK3 complex, and 17 beta estradiol–MAPK3 complex had relatively good binding stability. Our research sheds light on the immunomodulatory mechanism of deer antlers and provides a theoretical foundation for further exploration of their active compounds.

The rapid rise of multidrug-resistant (MDR) bacteria has once again caused bacterial infections to become a global health concern. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), offer a viable solution to these pathogens due to their diverse mechanisms of actions, which include direct killing as well as immunomodulatory properties (e.g., anti-inflammatory activity). HDPs may hence provide a more robust treatment of bacterial infections. In this review, the advent of and the mechanisms that lead to antibiotic resistance will be described. HDP mechanisms of antibacterial and immunomodulatory action will be presented, with specific examples of how the HDP aurein 2.2 and a few of its derivatives, namely peptide 73 and cG4L73, function. Finally, resistance that may arise from a broader use of HDPs in a clinical setting and methods to improve biocompatibility will be briefly discussed.

Pleurotus citrinopileatus, a valuable edible fungus characterized by its distinctive light yellow coloration and saprophytic growth on elm wood, has garnered increasing scientific interest due to its diverse bioactive constituents. Among these, polysaccharides derived from P. citrinopileatus (PCPs) have received the most extensive research attention. This review summarizes recent advances in the chemical structure and biological activities of PCPs. Structurally, PCPs are primarily composed of repeating units such as →3)-α-D-Glcp-(1→ and →6)-α-D-Galp-(1→. Functionally, PCPs exhibit a range of bioactivities, including immunomodulatory, hypoglycemic, and antitumor effects. Furthermore, the underlying mechanisms associated with these biological activities are also explored. This review aims to provide a comprehensive reference for future studies and facilitate the development and application of PCPs as potential functional food ingredients or therapeutic agents.

Peptides derived from non-immune proteins showed potent in vitro antimicrobial activity.Nearly 90% of peptides tested exhibited immunomodulatory effects.Lead peptides displayed anti-infective efficacy in preclinical mouse models, effectively reducing infections. Encrypted peptides (EPs) have been recently described as a new class of antimicrobial molecules. They have been found in numerous organisms and have been proposed to have a role in host immunity and as alternatives to conventional antibiotics. Intriguingly, many of these EPs are found embedded in proteins unrelated to the immune system, suggesting that immunological responses extend beyond traditional host immunity proteins. To test this idea, we synthesized and analyzed representative peptides derived from non-immune human proteins for their ability to exert antimicrobial and immunomodulatory properties. Most of the tested peptides from non-immune proteins, derived from structural proteins as well as proteins from the nervous and visual systems, displayed potent in vitro antimicrobial activity. These molecules killed bacterial pathogens by targeting their membrane, and those originating from the same region of the body exhibited synergistic effects when combined. Beyond their antimicrobial properties, nearly 90% of the peptides tested exhibited immunomodulatory effects, modulating inflammatory mediators, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein-1 (MCP-1). Moreover, eight of the peptides identified, collagenin-3 and 4, zipperin-1 and 2, and immunosin-2, 3, 12, and 13, displayed anti-infective efficacy in two different preclinical mouse models, reducing bacterial infections by up to four orders of magnitude. Altogether, our results support the hypothesis that peptides from non-immune proteins may have a role in host immunity. These results potentially expand our notion of the immune system to include previously unrecognized proteins and peptides that may be activated upon infection to confer protection to the host. [Display omitted] The exploration of encrypted peptides and their antimicrobial properties has progressed over nearly a decade, now achieving Technology Readiness Levels 3/4 in laboratory settings. While these advances are promising, significant challenges must be addressed before full-scale implementation is feasible. The primary challenge lies in experimentally validating the in vivo expression and cleavage of parent proteins into encrypted peptides, either individually or in combination, at levels sufficient to exhibit antimicrobial activity. Key areas for further investigation include: (i) Overexpression studies: non-immune-related parent proteins should be overexpressed to determine whether the encrypted peptides exhibit the expected antimicrobial activity when produced at physiological levels. (ii) Knockout models: developing knockout models lacking the parent proteins of encrypted peptides could provide direct evidence of their functional roles by observing whether bacterial proliferation increases in their absence. (iii) In vivo experiments: using knockout mouse strains in in vivo experiments could reveal whether these animals show increased susceptibility to pathogenic infections, thereby validating the protective role of these peptides. Additionally, these peptides can be further explored and chemically modified to create more stable derivatives for direct application in clinical infection scenarios. However, transitioning from laboratory research to practical applications will require addressing key challenges, including optimizing peptide stability, bioavailability, and safety. Encrypted peptides derived from non-immune proteins exhibit potent antimicrobial and immunomodulatory properties. These peptides effectively kill bacterial pathogens, modulate immune mediators, and show anti-infective efficacy in preclinical models. The findings suggest that host immunity extends beyond traditional immune proteins, potentially broadening our current understanding of the immune system.

A robust, well-functioning immune system is the cornerstone of good health. Various factors may influence the immune system’s effectiveness, potentially leading to immune system failure. This review aims to provide an overview of the structure and action of immunomodulators isolated from African medicinal plants. The research was conducted according to PRISMA guidelines. Full-text access research articles published in English up to December 2023, including plant characteristics, isolated phytochemicals, and immuno-modulatory activities, were screened. The chemical structures of the isolated compounds were generated using ChemDraw® (version 12.0.1076), and convergent and distinctive signaling pathways were highlighted. These phytochemicals with demonstrated immunostimulatory activity include alkaloids (berberine, piperine, magnoflorine), polysaccharides (pectin, glucan, acemannan, CALB-4, GMP90-1), glycosides (syringin, cordifolioside, tinocordiside, aucubin), phenolic compounds (ferulic acid, vanillic acid, eupalitin), flavonoids (curcumin, centaurein, kaempferin, luteolin, guajaverin, etc.), terpenoids (oleanolic acid, ursolic acid, betulinic acid, boswellic acids, corosolic acid, nimbidin, andrographolides). These discussed compounds exert their effects through various mechanisms, targeting the modulation of MAPKs, PI3K-Akt, and NF-kB. These mechanisms can support the traditional use of medicinal plants to treat immune-related diseases. The outcomes of this overview are to provoke structural action optimization, to orient research on particular natural chemicals for managing inflammatory, infectious diseases and cancers, or to boost vaccine immunogenicity.