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The Role of Natural Products in the Health System

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (15 January 2024) | Viewed by 7186

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Prof. Dr. Balik Dzhambazov

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Faculty of Biology, Plovdiv University “Paisii Hilendarski”, 24 Tsar Assen Str., 4000 Plovdiv, Bulgaria
Interests: cell biology; immunology; immunomodulation; biomarkers; autoimmune diseases; allergy; cytotoxicity; anticancer activity; natural products; probiotics; prebiotics; nanoparticles
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Dear Colleagues,

Natural products are individual molecules or a complex of compounds isolated from natural sources that possess certain valuable properties or biological activity. A large part of natural products are used as medicines for the treatment of various diseases, and another part is used in the food and cosmetic industry to improve one’s quality of life.

This Special Issue aims to publish original studies related to the isolation and characterization of new natural products and the determination of their biological or immunomodulatory activity, as well as their molecular mechanisms of action or effects on specific systems, metabolic or signaling pathways. Authors are invited to submit their high-quality articles, reviews or short communications on this topic. Multidisciplinary studies that involve in vitro and/or in vivo experiments aimed at specifically improving health status by using various new technologies based on natural products are also welcome.

Importantly, active natural molecules/compounds must be identified and characterized. Papers that describe the effects of mixed plant extracts will not be accepted.

Prof. Dr. Balik Dzhambazov
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
bioactivity
anticancer activity
apoptosis
immunomodulation
proliferation
probiotics
phytomolecules
nanoparticles
drug delivery

Published Papers (6 papers)

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Research

15 pages, 1387 KiB

Open AccessArticle

Effect of Caffeine on the Inflammatory-Dependent Changes in the GnRH/LH Secretion in a Female Sheep Model

by Andrzej Przemysław Herman, Monika Tomczyk, Maciej Wójcik, Joanna Bochenek, Hanna Antushevich, Anna Herman, Wiktoria Wiechetek, Aleksandra Szczepkowska, Elżbieta Marciniak and Dorota Tomaszewska-Zaremba

Int. J. Mol. Sci. 2024, 25(5), 2663; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25052663 - 25 Feb 2024

Viewed by 600

Abstract

Caffeine is one of the most widely consumed psychoactive drugs in the world. It easily crosses the blood–brain barrier, and caffeine-interacting adenosine and ryanodine receptors are distributed in various areas of the brain, including the hypothalamus and pituitary. Caffeine intake may have an impact on reproductive and immune function. Therefore, in the present study performed on the ewe model, we decided to investigate the effect of peripheral administration of caffeine (30 mg/kg) on the secretory activity of the hypothalamic–pituitary unit which regulates the reproductive function in females during both a physiological state and an immune/inflammatory challenge induced by lipopolysaccharide (LPS; 400 ng/kg) injection. It was found that caffeine stimulated (p < 0.01) the biosynthesis of gonadotropin-releasing hormone (GnRH) in the hypothalamus of ewe under both physiological and inflammatory conditions. Caffeine also increased (p < 0.05) luteinizing hormone (LH) secretion in ewes in a physiological state; however, a single administration of caffeine failed to completely release the LH secretion from the inhibitory influence of inflammation. This could result from the decreased expression of GnRHR in the pituitary and it may also be associated with the changes in the concentration of neurotransmitters in the median eminence (ME) where GnRH neuron terminals are located. Caffeine and LPS increased (p < 0.05) dopamine in the ME which may explain the inhibition of GnRH release. Caffeine treatment also increased (p < 0.01) cortisol release, and this stimulatory effect was particularly evident in sheep under immunological stress. Our studies suggest that caffeine affects the secretory activity of the hypothalamic–pituitary unit, although its effect appears to be partially dependent on the animal’s immune status. Full article

(This article belongs to the Special Issue The Role of Natural Products in the Health System)

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15 pages, 1437 KiB

Open AccessArticle

Cannabidiol at Nanomolar Concentrations Negatively Affects Signaling through the Adenosine A_2A Receptor

by Iu Raïch, Jaume Lillo, Carlos Ferreiro-Vera, Verónica Sánchez de Medina, Gemma Navarro and Rafael Franco

Int. J. Mol. Sci. 2023, 24(24), 17500; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242417500 - 15 Dec 2023

Viewed by 888

Abstract

Cannabidiol (CBD) is a phytocannabinoid with potential as a therapy for a variety of diseases. CBD may act via cannabinoid receptors but also via other G-protein-coupled receptors (GPCRs), including the adenosine A_2A receptor. Homogenous binding and signaling assays in Chinese hamster ovary (CHO) cells expressing the human version of the A_2A receptor were performed to address the effect of CBD on receptor functionality. CBD was not able to compete for the binding of a SCH 442416 derivative labeled with a red emitting fluorescent probe that is a selective antagonist that binds to the orthosteric site of the receptor. However, CBD reduced the effect of the selective A_2A receptor agonist, CGS 21680, on G_s-coupling and on the activation of the mitogen activated kinase signaling pathway. It is suggested that CBD is a negative allosteric modulator of the A_2A receptor. Full article

(This article belongs to the Special Issue The Role of Natural Products in the Health System)

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14 pages, 4781 KiB

Open AccessArticle

Fisetin Inhibits UVA-Induced Expression of MMP-1 and MMP-3 through the NOX/ROS/MAPK Pathway in Human Dermal Fibroblasts and Human Epidermal Keratinocytes

by Hye-Yeon Jang, Gi-Beum Kim, Jeong-Mi Kim, Sang Yull Kang, Hyun-Jo Youn, Jinny Park, Su Yeon Ro, Eun-Yong Chung, Kwang-Hyun Park and Jong-Suk Kim

Int. J. Mol. Sci. 2023, 24(24), 17358; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242417358 - 11 Dec 2023

Viewed by 1068

Abstract

Fisetin is a flavonoid found in plants and has been reported to be effective in various human diseases. However, the effective mechanisms of ultraviolet-A (UVA)-mediated skin damage are not yet clear. In this study, we investigated the protective mechanisms of fisetin regarding UVA-induced human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs) damages. Fisetin showed a cytoprotective effect against UVA irradiation and suppressed matrix metalloproteinases (MMPs), MMP-1, and MMP-3 expression. In addition, fisetin was rescued, which decreased mRNA levels of pro-inflammatory cytokines, reactive oxygen species production, and the downregulation of MAPK/AP-1 related protein and NADPH oxidase (NOX) mRNA levels. Furthermore, UVA-induced MMP-1 and MMP-3 were effectively inhibited by siRNAs to NOX 1 to 5 in HDFs and HEKs. These results indicate that fisetin suppresses UVA-induced damage through the NOX/ROS/MAPK pathway in HDFs and HEKs. Full article

(This article belongs to the Special Issue The Role of Natural Products in the Health System)

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23 pages, 3993 KiB

Open AccessArticle

Lentinula edodes Cultured Extract and Rouxiella badensis subsp. acadiensis (Canan SV-53) Intake Alleviates Immune Deregulation and Inflammation by Modulating Signaling Pathways and Epigenetic Mechanisms

by Roghayeh Shahbazi, Hamed Yasavoli-Sharahi, Nawal Alsadi, Farzaneh Sharifzad, Sandra Fang, Cyrille Cuenin, Vincent Cahais, Felicia Fei-Lei Chung, Zdenko Herceg and Chantal Matar

Int. J. Mol. Sci. 2023, 24(19), 14610; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241914610 - 27 Sep 2023

Viewed by 1290

Abstract

Puberty is a critical developmental period of life characterized by marked physiological changes, including changes in the immune system and gut microbiota development. Exposure to inflammation induced by immune stressors during puberty has been found to stimulate central inflammation and lead to immune disturbance at distant sites from the gut; however, its enduring effects on gut immunity are not well explored. Therefore, in this study, we used a pubertal lipopolysaccharides (LPS)-induced inflammation mouse model to mimic pubertal exposure to inflammation and dysbiosis. We hypothesized that pubertal LPS-induced inflammation may cause long-term dysfunction in gut immunity by enduring dysregulation of inflammatory signaling and epigenetic changes, while prebiotic/probiotic intake may mitigate the gut immune system deregulation later in life. To this end, four-week-old female Balb/c mice were fed prebiotics/probiotics and exposed to LPS in the pubertal window. To better decipher the acute and enduring immunoprotective effects of biotic intake, we addressed the effect of treatment on interleukin (IL)-17 signaling related-cytokines and pathways. In addition, the effect of treatment on gut microbiota and epigenetic alterations, including changes in microRNA (miRNA) expression and DNA methylation, were studied. Our results revealed a significant dysregulation in selected cytokines, proteins, and miRNAs involved in key signaling pathways related to IL-17 production and function, including IL-17A and F, IL-6, IL-1β, transforming growth factor-β (TGF-β), signal transducer and activator of transcription-3 (STAT3), p-STAT3, forkhead box O1 (FOXO1), and miR-145 in the small intestine of adult mice challenged with LPS during puberty. In contrast, dietary interventions mitigated the lasting adverse effects of LPS on gut immune function, partly through epigenetic mechanisms. A DNA methylation analysis demonstrated that enduring changes in gut immunity in adult mice might be linked to differentially methylated genes, including Lpb, Rorc, Runx1, Il17ra, Rac1, Ccl5, and Il10, involved in Th17 cell differentiation and IL-17 production and signaling. In addition, prebiotic administration prevented LPS-induced changes in the gut microbiota in pubertal mice. Together, these results indicate that following a healthy diet rich in prebiotics and probiotics is an optimal strategy for programming immune system function in the critical developmental windows of life and controlling inflammation later in life. Full article

(This article belongs to the Special Issue The Role of Natural Products in the Health System)

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14 pages, 504 KiB

Open AccessArticle

Glycosylation of Quercetin by Selected Entomopathogenic Filamentous Fungi and Prediction of Its Products’ Bioactivity

by Tomasz Tronina, Mateusz Łużny, Monika Dymarska, Monika Urbaniak, Ewa Kozłowska, Michał Piegza, Łukasz Stępień and Tomasz Janeczko

Int. J. Mol. Sci. 2023, 24(14), 11857; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241411857 - 24 Jul 2023

Cited by 3 | Viewed by 1160

Abstract

Quercetin is the most abundant flavonoid in food products, including berries, apples, cauliflower, tea, cabbage, nuts, onions, red wine and fruit juices. It exhibits various biological activities and is used for medical applications, such as treating allergic, inflammatory and metabolic disorders, ophthalmic and cardiovascular diseases, and arthritis. However, its low water solubility may limit quercetin’s therapeutic potential. One method of increasing the solubility of active compounds is their coupling to polar molecules, such as sugars. The attachment of a glucose unit impacts the stability and solubility of flavonoids and often determines their bioavailability and bioactivity. Entomopathogenic fungi are biocatalysts well known for their ability to attach glucose and its 4-O-methyl derivative to bioactive compounds, including flavonoids. We investigated the ability of cultures of entomopathogenic fungi belonging to Beauveria, Isaria, Metapochonia, Lecanicillium and Metarhizium genera to biotransform quercetin. Three major glycosylation products were detected: (1), 7-O-β-D-(4″-O-methylglucopyranosyl)-quercetin, (2) 3-O-β-D-(4″-O-methylglucopyranosyl)-quercetin and (3) 3-O-β-D-(glucopyranosyl)-quercetin. The results show evident variability of the biotransformation process, both between strains of the tested biocatalysts from different species and between strains of the same species. Pharmacokinetic and pharmacodynamic properties of the obtained compounds were predicted with the use of cheminformatics tools. The study showed that the obtained compounds may have applications as effective modulators of intestinal flora and may be stronger hepato-, cardio- and vasoprotectants and free radical scavengers than quercetin. Full article

(This article belongs to the Special Issue The Role of Natural Products in the Health System)

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11 pages, 1224 KiB

Open AccessCommunication

Ethyl Caffeate Can Inhibit Aryl Hydrocarbon Receptor (AhR) Signaling and AhR-Mediated Potentiation of Mast Cell Activation

by Phuc-Tan Nguyen, Yuki Nakamura, Nguyen Quoc Vuong Tran, Kayoko Ishimaru, Thuy-An Nguyen, Yoshiaki Kobayashi, Fumie Watanabe-Saito, Tohru Okuda, Nobuhiro Nakano and Atsuhito Nakao

Int. J. Mol. Sci. 2023, 24(12), 9997; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24129997 - 10 Jun 2023

Viewed by 1289

Abstract

Ethyl caffeate (EC) is a natural phenolic compound that is present in several medicinal plants used to treat inflammatory disorders. However, its anti-inflammatory mechanisms are not fully understood. Here, we report that EC inhibits aryl hydrocarbon receptor (AhR) signaling and that this is associated with its anti-allergic activity. EC inhibited AhR activation, induced by the AhR ligands FICZ and DHNA in AhR signaling-reporter cells and mouse bone marrow-derived mast cells (BMMCs), as assessed by AhR target gene expressions such as CYP1A1. EC also inhibited the FICZ-induced downregulation of AhR expression and DHNA-induced IL-6 production in BMMCs. Furthermore, the pretreatment of mice with orally administered EC inhibited DHNA-induced CYP1A1 expression in the intestine. Notably, both EC and CH-223191, a well-established AhR antagonist, inhibited IgE-mediated degranulation in BMMCs grown in a cell culture medium containing significant amounts of AhR ligands. Furthermore, oral administration of EC or CH-223191 to mice inhibited the PCA reaction associated with the suppression of constitutive CYP1A1 expression within the skin. Collectively, EC inhibited AhR signaling and AhR-mediated potentiation of mast cell activation due to the intrinsic AhR activity in both the culture medium and normal mouse skin. Given the AhR control of inflammation, these findings suggest a novel mechanism for the anti-inflammatory activity of EC. Full article

(This article belongs to the Special Issue The Role of Natural Products in the Health System)

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