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Applied Sciences
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Novel Approaches for Natural Product-Derived Immunomodulators
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Novel Approaches for Natural Product-Derived Immunomodulators

A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Biomedical Engineering".

Deadline for manuscript submissions: 20 April 2024 | Viewed by 16700

Special Issue Editor

Dr. Owen Kavanagh

E-Mail Website
Guest Editor
Senior Lecturer in Biomedical Sciences, School of Science, Technology and Health, York St John University, Lord Mayor’s Walk, York YO31 7EX, UK
Interests: natural products; immunomodulators; vaccines; biomarkers in health and disease

Special Issue Information

Dear Colleagues,

Natural products are any molecule produced by a natural source and are the origin of many drugs used in modern human and veterinary medicine. In addition, there is a growing demand for novel drugs, especially in the face of major global health challenges such as antimicrobial resistance and limited efficacy of chemotherapeutics. This vast reservoir of natural biomolecules could be mined to reveal a plethora of new drugs needed to combat humanity’s greatest challenges. Furthermore, bioactive molecule efficacy can be enhanced by exploiting novel extraction, chemical and genomic techniques.

Immunomodulators are one such class of NP-derived biological response modifiers that can influence both arms of the vertebrate immune system positively (immunostimulant) or negatively (immunosuppressant). Immunostimulants can be used as vaccine adjuvants, anti-cancer agents and to prevent infections in humans and livestock, whereas immunosuppressants can counteract immune hypersensitivities, autoimmunity, cancer immunotherapy and organ transplant rejection. These drugs tend to be expensive and exhibit undesirable safety profiles and so new candidate therapeutics are urgently required.

In this context of this Special Issue, we invite authors to submit high-quality original research articles, comprehensive review papers or short communications on Novel Approaches for Natural Immunomodulators. Research articles that address all aspects this field using a combination of different novel technologies or combinations of novel with conventional technologies are also welcome.

Dr. Owen Kavanagh
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Applied Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • natural products
  • plants
  • phytochemical
  • bacteria
  • archaea
  • fungi
  • insects and arachnids
  • animals
  • marine organisms
  • immunostimulant
  • immunosuppressant
  • biological response modifiers

Published Papers (7 papers)

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Research

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18 pages, 10804 KiB  
Article
A Novel Approach for Fast Screening of a Complex Cyanobacterial Extract for Immunomodulatory Properties and Antibacterial Activity
by Ivanka Teneva, Tsvetelina Batsalova, Krum Bardarov, Dzhemal Moten and Balik Dzhambazov
Appl. Sci. 2022, 12(6), 2847; https://0-doi-org.brum.beds.ac.uk/10.3390/app12062847 - 10 Mar 2022
Cited by 2 | Viewed by 1551
Abstract
The filamentous cyanobacteria from genus Phormidium are rich natural sources of bioactive compounds that could be exploited as pharmaceuticals or nutraceuticals. In this study, we suggest a novel approach for assessing the immunomodulatory properties of the products derived from cyanobacteria. The influence of [...] Read more.
The filamentous cyanobacteria from genus Phormidium are rich natural sources of bioactive compounds that could be exploited as pharmaceuticals or nutraceuticals. In this study, we suggest a novel approach for assessing the immunomodulatory properties of the products derived from cyanobacteria. The influence of Phormidium papyraceum extract on the human leukocyte immunophenotype was evaluated by attempting to link this activity to certain putative compounds identified in the extract. By using three staining panels and flow cytometry, we found that the cyanobacterial extract affected mainly CD4+ T cells upregulating activated CD4+CD152+ T cells (15.75 ± 1.93% treated vs. 4.65 ± 1.41% control) and regulatory CD4+CD25+ T cells (5.36 ± 0.64% treated vs. 1.03 ± 0.08% control). Furthermore, P. papyraceum extract can modulate T cell subpopulations with a CD4+ effector/memory phenotype. Extract-treated cells showed increased production of IL-2 (55 ± 12 pg/mL) and IL-6 (493 ± 64 pg/mL) compared to the untreated, 21 ± 7 pg/mL and 250 ± 39 pg/mL, respectively. No significant changes were observed in the secretion of TNF-α. In addition, P. papyraceum extract displayed antibacterial activity against both Gram-negative (inhibition zone from 18.25 ± 0.50 mm to 20.28 ± 1.50 mm) and Gram-positive (inhibition zone from 10.86 ± 0.85 mm to 17.00 ± 0.82 mm) bacteria. The chemical profile of the cyanobacterial extract was determined using LC–ESI–MS/MS analysis, where at least 112 putative compounds were detected. Many of these compounds have proven different biological activities. We speculated that compounds such as betulin and the macrolide azithromycin (or their analogues) could be responsible for the immunomodulatory potential of the investigated extract. More studies are needed to determine and validate the biological activities of the determined putative compounds. Full article
(This article belongs to the Special Issue Novel Approaches for Natural Product-Derived Immunomodulators)
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Review

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21 pages, 1550 KiB  
Review
Is Probiotics Supplementation an Appropriate Strategy to Modulate Inflammation in Physically Active Healthy Adults or Athletes? A Systematic Review
by Diego Fernández-Lázaro, Nerea Sánchez-Serrano, Roshina Rabail, Rana Muhammad Aadil, Juan Mielgo-Ayuso, Krizia Radesca Fabiano and Evelina Garrosa
Appl. Sci. 2023, 13(6), 3448; https://0-doi-org.brum.beds.ac.uk/10.3390/app13063448 - 08 Mar 2023
Cited by 2 | Viewed by 1756
Abstract
Supplementation with probiotics in sports is on the rise with the aim of improving health and athletic performance. Since intense exercise-induced muscle damage leads to an inflammatory process by increasing circulating inflammatory cytokines, probiotic supplementation may modulate and correct the inflammation. We systematically [...] Read more.
Supplementation with probiotics in sports is on the rise with the aim of improving health and athletic performance. Since intense exercise-induced muscle damage leads to an inflammatory process by increasing circulating inflammatory cytokines, probiotic supplementation may modulate and correct the inflammation. We systematically reviewed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the Scopus, Web of Science, and Medline databases for the 10 years until January 2023. This review aimed to evaluate probiotic supplementation as a strategy for modulating inflammation in healthy physically active adults or athletes. Studies were indexed to assess the effect of probiotic supplementation on cytokine behavior in the inflammatory response in physically active individuals. Of the 136 studies identified in the search, 13 met the inclusion criteria, and their quality was assessed using the McMaster Critical Review Form. The results of these trials indicated a significant improvement in inflammatory cytokines in probiotic-supplemented participants, with a significant increase in anti-inflammatory cytokines (IL-10) and a significant decrease in proinflammatory cytokines (IL-6, TNF-α, and IL-8). This would create uncertainty about probiotics’ effect on interleukins’ behavior after exercise, and further clinical trials are needed to establish a solid basis. Full article
(This article belongs to the Special Issue Novel Approaches for Natural Product-Derived Immunomodulators)
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20 pages, 971 KiB  
Review
The Use of Phytochemicals to Improve the Efficacy of Immune Checkpoint Inhibitors: Opportunities and Challenges
by Deniz Can Guven, Taha Koray Sahin, Alessandro Rizzo, Angela Dalia Ricci, Sercan Aksoy and Kazim Sahin
Appl. Sci. 2022, 12(20), 10548; https://0-doi-org.brum.beds.ac.uk/10.3390/app122010548 - 19 Oct 2022
Viewed by 1768
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and reshaped medical oncology practice over the past decade. However, despite unprecedented and durable clinical responses, most patients eventually fail to respond to ICI therapy due to primary or acquired resistance. There is a great [...] Read more.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and reshaped medical oncology practice over the past decade. However, despite unprecedented and durable clinical responses, most patients eventually fail to respond to ICI therapy due to primary or acquired resistance. There is a great need for complementary alternative medicine, such as botanicals and nutritional supplements, because of their capability to modulate a myriad of molecular mechanisms to prevent immunotherapy resistance and reduce its adverse effects. Mounting evidence suggests that phytochemicals, biologically active compounds derived from plants, can favorably regulate key signaling pathways involved in tumor development and progression. In addition, phytochemicals have been found to exert anticancer effects by altering the expression of checkpoint inhibitors of the immune response. The immunomodulatory activity of phytochemicals in the tumor microenvironment has recently received immense interest. Based on these immunomodulatory activities, phytochemicals could be candidates for combination with ICIs in future clinical studies. The current review focuses on the available evidence for combining phytochemicals with a discussion on the promising opportunities to enhance the efficacy of immune checkpoint inhibitors and potential challenges resulting from these combinations. Full article
(This article belongs to the Special Issue Novel Approaches for Natural Product-Derived Immunomodulators)
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19 pages, 386 KiB  
Review
β-Glucans from Yeast—Immunomodulators from Novel Waste Resources
by Scintilla Thomas, Emanuele Rezoagli, Ismin Zainol Abidin, Ian Major, Patrick Murray and Emma J. Murphy
Appl. Sci. 2022, 12(10), 5208; https://0-doi-org.brum.beds.ac.uk/10.3390/app12105208 - 21 May 2022
Cited by 13 | Viewed by 4331
Abstract
β-glucans are a large class of complex polysaccharides with bioactive properties, including immune modulation. Natural sources of these compounds include yeast, oats, barley, mushrooms, and algae. Yeast is abundant in various processes, including fermentation, and they are often discarded as waste products. The [...] Read more.
β-glucans are a large class of complex polysaccharides with bioactive properties, including immune modulation. Natural sources of these compounds include yeast, oats, barley, mushrooms, and algae. Yeast is abundant in various processes, including fermentation, and they are often discarded as waste products. The production of biomolecules from waste resources is a growing trend worldwide with novel waste resources being constantly identified. Yeast-derived β-glucans may assist the host’s defence against infections by influencing neutrophil and macrophage inflammatory and antibacterial activities. β-glucans were long regarded as an essential anti-cancer therapy and were licensed in Japan as immune-adjuvant therapy for cancer in 1980 and new mechanisms of action of these molecules are constantly emerging. This paper outlines yeast β-glucans’ immune-modulatory and anti-cancer effects, production and extraction, and their availability in waste streams. Full article
(This article belongs to the Special Issue Novel Approaches for Natural Product-Derived Immunomodulators)
19 pages, 2156 KiB  
Review
Novel Insights into the Immunomodulatory Effects of Caryophyllane Sesquiterpenes: A Systematic Review of Preclinical Studies
by Marco Gullì, Ester Percaccio, Silvia Di Giacomo and Antonella Di Sotto
Appl. Sci. 2022, 12(5), 2292; https://0-doi-org.brum.beds.ac.uk/10.3390/app12052292 - 22 Feb 2022
Cited by 4 | Viewed by 1864
Abstract
Immunomodulation is a key factor in the homeostasis of organisms, both for physiological and inflammatory conditions. In this context, great attention has been devoted to immunomodulant agents, which can boost or modulate the immune system, thus favoring disease relief. The present systematic review [...] Read more.
Immunomodulation is a key factor in the homeostasis of organisms, both for physiological and inflammatory conditions. In this context, great attention has been devoted to immunomodulant agents, which can boost or modulate the immune system, thus favoring disease relief. The present systematic review is focused on the immunomodulatory properties of plant-based caryophyllane sesquiterpenes, which are unique natural compounds widely studied due to their multiple and pleiotropic bioactivities. Despite lacking clinical evidence, the selected studies highlighted the ability of these substances, especially β-caryophyllene and α-humulene, to modulate the immune system of both in vitro and in vivo models of disease, such as neurodegenerative and inflammatory-based diseases, cancer, and allergies; moreover, some mechanistic hypotheses have been made too. The present overview suggests a further interest in immunomodulation by caryophyllane sesquiterpenes as a possible novel strategy for immune-based diseases or as an adjuvant treatment and encourages further high-quality studies, using high-purity compounds, to better clarify the mechanisms accounting for these properties and to support a further pharmaceutical development. Full article
(This article belongs to the Special Issue Novel Approaches for Natural Product-Derived Immunomodulators)
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14 pages, 1887 KiB  
Review
Probiotic Molecules That Inhibit Inflammatory Diseases
by Jesus Zamora-Pineda, Olga Kalinina, Barbara A. Osborne and Katherine L. Knight
Appl. Sci. 2022, 12(3), 1147; https://0-doi-org.brum.beds.ac.uk/10.3390/app12031147 - 22 Jan 2022
Cited by 4 | Viewed by 2028
Abstract
Consumption of probiotics for health purposes has increased vastly in the past few decades, and yet the scientific evidence to support health benefits from probiotics is only beginning to emerge. As more probiotics are studied, we are beginning to understand the mechanisms of [...] Read more.
Consumption of probiotics for health purposes has increased vastly in the past few decades, and yet the scientific evidence to support health benefits from probiotics is only beginning to emerge. As more probiotics are studied, we are beginning to understand the mechanisms of action by which they benefit human health, as well as to identify the bacterial molecules responsible for these benefits. A new era of therapeutics is on the horizon in which purified molecules from probiotics will be used to prevent and treat diseases. In this review, we summarize the active molecules from probiotic bacteria that have been shown to affect innate and adaptive immunity and have health benefits in experimental settings. We focus particularly on the cellular and molecular mechanisms of the probiotic Bacillus subtilis and its active molecule, exopolysaccharide (ESPBs). Full article
(This article belongs to the Special Issue Novel Approaches for Natural Product-Derived Immunomodulators)
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Other

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16 pages, 608 KiB  
Systematic Review
Galleria mellonella as a Novel In Vivo Model to Screen Natural Product-Derived Modulators of Innate Immunity
by Claire Louise Wright and Owen Kavanagh
Appl. Sci. 2022, 12(13), 6587; https://0-doi-org.brum.beds.ac.uk/10.3390/app12136587 - 29 Jun 2022
Cited by 11 | Viewed by 2039
Abstract
Immunomodulators are drugs that either stimulate or suppress the immune system in response to an immunopathological disease or cancer. The majority of clinically approved immunomodulators are either chemically synthesised (e.g., dexamethasone) or protein-based (e.g., monoclonal antibodies), whose uses are limited due to toxicity [...] Read more.
Immunomodulators are drugs that either stimulate or suppress the immune system in response to an immunopathological disease or cancer. The majority of clinically approved immunomodulators are either chemically synthesised (e.g., dexamethasone) or protein-based (e.g., monoclonal antibodies), whose uses are limited due to toxicity issues, poor bioavailability, or prohibitive cost. Nature is an excellent source of novel compounds, as it is estimated that almost half of all licenced medicines are derived from nature or inspired by natural product (NP) structures. The clinical success of the fungal-derived immunosuppressant cyclosporin A demonstrates the potential of natural products as immunomodulators. Conventionally, the screening of NP molecules for immunomodulation is performed in small animal models; however, there is a growing impetus to replace animal models with more ethical alternatives. One novel approach is the use of Galleria melonella larvae as an in vivo model of immunity. Despite lacking adaptive antigen-specific immunity, this insect possesses an innate immune system comparable to mammals. In this review, we will describe studies that have used this alternative in vivo model to assess the immunomodulating activity of synthetic and NP-derived compounds, outline the array of bioassays employed, and suggest strategies to enhance the use of this model in future research. Full article
(This article belongs to the Special Issue Novel Approaches for Natural Product-Derived Immunomodulators)
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