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Biological Properties of Secondary Metabolites and Natural Compounds
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Biological Properties of Secondary Metabolites and Natural Compounds

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

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 80830

Special Issue Editors

Dr. Ignazio Barbagallo

E-Mail Website1 Website2
Guest Editor
Department of Drug Science, Biochemistry Section, University of Catania, Catania, Italy
Interests: inflammation; cell differentiation; butrition; oxidative stress; natural compounds in cancer; degenerative and metabolic disease; aging
Dr. Rosa Palmeri

E-Mail Website
Guest Editor
Department of Agriculture Food and Environment (Di3A), University of Catania, Catania, Italy
Interests: food science and technology; food industry applications; plant extracts; shelf life; food quality; microbial safety
Special Issues, Collections and Topics in MDPI journals
Dr. Aldo Todaro

E-Mail Website
Guest Editor
Dipartimento di Agricoltura, Alimentazione e Ambiente, University of Catania, Via S. Sofia 100, 95123 Catania, Italy
Interests: fruit quality; horticultural physiology and preservation recovery of high value compounds from food processing wastes; fruit processing
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Barbara Tomasello

E-Mail Website1 Website2
Guest Editor
1. Department of Drug and Health Sciences, Section of Biochemistry, University of Catania, 95125 Catania, Italy
2. Research Center on Nutraceuticals and Health Products (CERNUT), University of Catania, 95125 Catania, Italy
3. Molecular, Preclinical and Translational Imaging Research Centre (IMPRONTE), University of Catania, 95125 Catania, Italy
Interests: nutraceuticals; cancer biology; biomarkers; oxidative stress and natural compounds in cancer, aging, degenerative and metabolic disease; cancer epigenetics; DNA damage and comet assay; inflammation; nanosystem for drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Currently, there is a growing interest in finding new bioactive natural compounds that can be exploited for their potential role in counteracting human diseases and certain types of cancer. Bioactive natural compounds are secondary metabolites synthesized from plants, bacteria, or fungi, often synthetized in response to stress conditions. They include different classes of compounds with different chemical structures, including polyphenols, carotenoids, tocopherols, phytosterols, organosulfur compounds, and others.

Several studies have focused on beneficial effects in vitro, in vivo, and in clinical studies of natural compounds and secondary metabolites in order to determine the effects on health/disease risk endpoints.

This Special Issue welcomes both original papers and reviews focusing on use or potential of bioactive natural compounds in human disease prevention and therapy.

The following keywords may be useful in selecting a paper topic:

  • botanical compounds
  • oxidative stress
  • inflammation
  • infection
  • metabolic syndrome
  • cancer
  • chronic disorders
  • neurodegenerative diseases
  • aging-associated disorders
  • gastrointestinal dysfunction
  • integrative medicine
  • functional food

Dr. Ignazio Barbagallo
Prof. Rosa Palmeri
Prof. Aldo Todaro
Prof. Barbara Tomasello
Guest Editors

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.

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (8 papers)

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Research

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11 pages, 1284 KiB  
Article
Baicalin-Induced Autophagy Preserved LPS-Stimulated Intestinal Cells from Inflammation and Alterations of Paracellular Permeability
by Valentina Rizzo, Nadia Ferlazzo, Monica Currò, Gaetano Isola, Marco Matarese, Maria Paola Bertuccio, Daniela Caccamo, Giovanni Matarese and Riccardo Ientile
Int. J. Mol. Sci. 2021, 22(5), 2315; https://doi.org/10.3390/ijms22052315 - 26 Feb 2021
Cited by 38 | Viewed by 4055
Abstract
Several studies have demonstrated a relevant role of intestinal epithelial cells in the immune response and in chronic inflammatory conditions, including ulcers, colitis, and Crohn’s disease. Baicalin (BA), extracted from the root of Scutellaria baicalensis, has various beneficial healthy effects, including anti-inflammatory activity. [...] Read more.
Several studies have demonstrated a relevant role of intestinal epithelial cells in the immune response and in chronic inflammatory conditions, including ulcers, colitis, and Crohn’s disease. Baicalin (BA), extracted from the root of Scutellaria baicalensis, has various beneficial healthy effects, including anti-inflammatory activity. However, few studies have evaluated BA effects on autophagic signaling in epithelial cell response to inflammatory stimuli. To explore possible beneficial effects of BA, HT-29 cells were exposed to lipopolysaccharide (LPS), in presence or absence of BA, for 4 h. We evaluated mRNA levels of autophagy-related genes and cytokines, triggering inflammatory response. Furthermore, the expression of claudin 1, involved in the regulation of paracellular permeability was analyzed. BA treatment repressed LPS-induced expression of TNF-α and IL-1β. The down-regulation of autophagy-related genes induced by LPS was counteracted by cell pretreatment with BA. Under these conditions, BA reduced the NF-κB activation caused by LPS. Also, BA restored mRNA and protein levels of claudin 1, which were reduced by LPS. In conclusion, in intestinal epithelial cells BA regulates the NF-κB activation and modulates both autophagic and inflammatory processes, leading to an improvement of paracellular permeability. These results suggest that the anti-inflammatory effects of BA can be associated to the regulation of autophagic flux. Full article
(This article belongs to the Special Issue Biological Properties of Secondary Metabolites and Natural Compounds)
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25 pages, 5167 KiB  
Article
Rapha Myr®, a Blend of Sulforaphane and Myrosinase, Exerts Antitumor and Anoikis-Sensitizing Effects on Human Astrocytoma Cells Modulating Sirtuins and DNA Methylation
by Barbara Tomasello, Maria Domenica Di Mauro, Giuseppe Antonio Malfa, Rosaria Acquaviva, Fulvia Sinatra, Giorgia Spampinato, Samuele Laudani, Giusy Villaggio, Anna Bielak-Zmijewska, Wioleta Grabowska, Ignazio Alberto Barbagallo, Maria Teresa Liuzzo, Elisabetta Sbisà, Maria Grazia Forte, Claudia Di Giacomo, Massimo Bonucci and Marcella Renis
Int. J. Mol. Sci. 2020, 21(15), 5328; https://doi.org/10.3390/ijms21155328 - 27 Jul 2020
Cited by 14 | Viewed by 4541
Abstract
Brain and other nervous system cancers are the 10th leading cause of death worldwide. Genome instability, cell cycle deregulation, epigenetic mechanisms, cytoarchitecture disassembly, redox homeostasis as well as apoptosis are involved in carcinogenesis. A diet rich in fruits and vegetables is inversely related [...] Read more.
Brain and other nervous system cancers are the 10th leading cause of death worldwide. Genome instability, cell cycle deregulation, epigenetic mechanisms, cytoarchitecture disassembly, redox homeostasis as well as apoptosis are involved in carcinogenesis. A diet rich in fruits and vegetables is inversely related with the risk of developing cancer. Several studies report that cruciferous vegetables exhibited antiproliferative effects due to the multi-pharmacological functions of their secondary metabolites such as isothiocyanate sulforaphane deriving from the enzymatic hydrolysis of glucosinolates. We treated human astrocytoma 1321N1 cells for 24 h with different concentrations (0.5, 1.25 and 2.5% v/v) of sulforaphane plus active myrosinase (Rapha Myr®) aqueous extract (10 mg/mL). Cell viability, DNA fragmentation, PARP-1 and γH2AX expression were examined to evaluate genotoxic effects of the treatment. Cell cycle progression, p53 and p21 expression, apoptosis, cytoskeleton morphology and cell migration were also investigated. In addition, global DNA methylation, DNMT1 mRNA levels and nuclear/mitochondrial sirtuins were studied as epigenetic biomarkers. Rapha Myr® exhibited low antioxidant capability and exerted antiproliferative and genotoxic effects on 1321N1 cells by blocking the cell cycle, disarranging cytoskeleton structure and focal adhesions, decreasing the integrin α5 expression, renewing anoikis and modulating some important epigenetic pathways independently of the cellular p53 status. In addition, Rapha Myr® suppresses the expression of the oncogenic p53 mutant protein. These findings promote Rapha Myr® as a promising chemotherapeutic agent for integrated cancer therapy of human astrocytoma. Full article
(This article belongs to the Special Issue Biological Properties of Secondary Metabolites and Natural Compounds)
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21 pages, 2512 KiB  
Article
A Global Cndp1-Knock-Out Selectively Increases Renal Carnosine and Anserine Concentrations in an Age- and Gender-Specific Manner in Mice
by Tim Weigand, Florian Colbatzky, Tilman Pfeffer, Sven F. Garbade, Kristina Klingbeil, Florian Colbatzky, Michael Becker, Johanna Zemva, Ruben Bulkescher, Robin Schürfeld, Christian Thiel, Nadine Volk, David Reuss, Georg F. Hoffmann, Marc Freichel, Markus Hecker, Tanja Poth, Thomas Fleming, Gernot Poschet, Claus P. Schmitt and Verena Petersadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2020, 21(14), 4887; https://doi.org/10.3390/ijms21144887 - 10 Jul 2020
Cited by 12 | Viewed by 4208
Abstract
Carnosinase 1 (CN1) is encoded by the Cndp1 gene and degrades carnosine and anserine, two natural histidine-containing dipeptides. In vitro and in vivo studies suggest carnosine- and anserine-mediated protection against long-term sequelae of reactive metabolites accumulating, e.g., in diabetes mellitus. We have characterized [...] Read more.
Carnosinase 1 (CN1) is encoded by the Cndp1 gene and degrades carnosine and anserine, two natural histidine-containing dipeptides. In vitro and in vivo studies suggest carnosine- and anserine-mediated protection against long-term sequelae of reactive metabolites accumulating, e.g., in diabetes mellitus. We have characterized the metabolic impact of CN1 in 11- and 55-week-old Cndp1-knockout (Cndp1-KO) mice and litter-matched wildtypes (WT). In Cndp1-KO mice, renal carnosine and anserine concentrations were gender-specifically increased 2- to 9-fold, respectively in the kidney and both most abundant in the renal cortex, but remained unchanged in all other organs and in serum. Renal oxidized/reduced glutathione concentrations, renal morphology and function were unaltered. In Cndp1-KO mice at week 11, renal asparagine, serine and glutamine levels and at week 55, renal arginine concentration were reduced. Renal heat-shock-protein 70 (Hspa1a/b) mRNA declined with age in WT but not in Cndp1-KO mice, transcription factor heat-shock-factor 1 was higher in 55-week-old KO mice. Fasting blood glucose concentrations decreased with age in WT mice, but were unchanged in Cndp1-KO mice. Blood glucose response to intraperitoneal insulin was gender- but not genotype-dependent, the response to intraperitoneal glucose injection was similar in all groups. A global Cndp1-KO selectively, age- and gender-specifically, increases renal carnosine and anserine concentrations, alters renal amino acid- and HSP70 profile and modifies systemic glucose homeostasis. Increase of the natural occurring carnosine and anserine levels in the kidney by modulation of CN1 represents a promising therapeutic approach to mitigate or prevent chronic kidney diseases such as diabetic nephropathy. Full article
(This article belongs to the Special Issue Biological Properties of Secondary Metabolites and Natural Compounds)
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Review

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19 pages, 805 KiB  
Review
Xanthohumol for Human Malignancies: Chemistry, Pharmacokinetics and Molecular Targets
by Vancha Harish, Effi Haque, Magdalena Śmiech, Hiroaki Taniguchi, Sarah Jamieson, Devesh Tewari and Anupam Bishayee
Int. J. Mol. Sci. 2021, 22(9), 4478; https://doi.org/10.3390/ijms22094478 - 25 Apr 2021
Cited by 57 | Viewed by 7321
Abstract
Xanthohumol (XH) is an important prenylated flavonoid that is found within the inflorescence of Humulus lupulus L. (Hop plant). XH is an important ingredient in beer and is considered a significant bioactive agent due to its diverse medicinal applications, which include anti-inflammatory, antimicrobial, [...] Read more.
Xanthohumol (XH) is an important prenylated flavonoid that is found within the inflorescence of Humulus lupulus L. (Hop plant). XH is an important ingredient in beer and is considered a significant bioactive agent due to its diverse medicinal applications, which include anti-inflammatory, antimicrobial, antioxidant, immunomodulatory, antiviral, antifungal, antigenotoxic, antiangiogenic, and antimalarial effects as well as strong anticancer activity towards various types of cancer cells. XH acts as a wide ranging chemopreventive and anticancer agent, and its isomer, 8-prenylnaringenin, is a phytoestrogen with strong estrogenic activity. The present review focuses on the bioactivity of XH on various types of cancers and its pharmacokinetics. In this paper, we first highlight, in brief, the history and use of hops and then the chemistry and structure–activity relationship of XH. Lastly, we focus on its prominent effects and mechanisms of action on various cancers and its possible use in cancer prevention and treatment. Considering the limited number of available reviews on this subject, our goal is to provide a complete and detailed understanding of the anticancer effects of XH against different cancers. Full article
(This article belongs to the Special Issue Biological Properties of Secondary Metabolites and Natural Compounds)
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30 pages, 408 KiB  
Review
Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials
by Giuseppe Venturella, Valeria Ferraro, Fortunato Cirlincione and Maria Letizia Gargano
Int. J. Mol. Sci. 2021, 22(2), 634; https://doi.org/10.3390/ijms22020634 - 10 Jan 2021
Cited by 264 | Viewed by 37055
Abstract
Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment [...] Read more.
Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment from the scientific community to expand clinical trials and to propose supplements of safe origin and genetic purity. Bioactive compounds of selected medicinal mushrooms and their effects and mechanisms in in vitro and in vivo clinical studies are reported in this review. Besides, we analyzed the therapeutic use and pharmacological activities of mushrooms. Full article
(This article belongs to the Special Issue Biological Properties of Secondary Metabolites and Natural Compounds)
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18 pages, 1838 KiB  
Review
Curcumin Metabolite Tetrahydrocurcumin in the Treatment of Eye Diseases
by Yu-Wen Kao, Sheng-Kai Hsu, Jeff Yi-Fu Chen, I-Ling Lin, Kuo-Jen Chen, Po-Yen Lee, Hui-Suan Ng, Chien-Chih Chiu and Kai-Chun Cheng
Int. J. Mol. Sci. 2021, 22(1), 212; https://doi.org/10.3390/ijms22010212 - 28 Dec 2020
Cited by 32 | Viewed by 6339
Abstract
Curcumin is one of the most valuable natural products due to its pharmacological activities. However, the low bioavailability of curcumin has long been a problem for its medicinal use. Large studies have been conducted to improve the use of curcumin; among these studies, [...] Read more.
Curcumin is one of the most valuable natural products due to its pharmacological activities. However, the low bioavailability of curcumin has long been a problem for its medicinal use. Large studies have been conducted to improve the use of curcumin; among these studies, curcumin metabolites have become a relatively new research focus over the past few years. Additionally, accumulating evidence suggests that curcumin or curcuminoid metabolites have similar or better biological activity than the precursor of curcumin. Recent studies focus on the protective role of plasma tetrahydrocurcumin (THC), a main metabolite of curcumin, against tumors and chronic inflammatory diseases. Nevertheless, studies of THC in eye diseases have not yet been conducted. Since ophthalmic conditions play a crucial role in worldwide public health, the prevention and treatment of ophthalmic diseases are of great concern. Therefore, the present study investigated the antioxidative, anti-inflammatory, antiangiogenic, and neuroprotective effects of THC on four major ocular diseases: age-related cataracts, glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). While this study aimed to show curcumin as a promising potential solution for eye conditions and discusses the involved mechanistic pathways, further work is required for the clinical application of curcumin. Full article
(This article belongs to the Special Issue Biological Properties of Secondary Metabolites and Natural Compounds)
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16 pages, 2857 KiB  
Review
Natural Salicylates and Their Roles in Human Health
by Fatema Yeasmin and Hyong Woo Choi
Int. J. Mol. Sci. 2020, 21(23), 9049; https://doi.org/10.3390/ijms21239049 - 28 Nov 2020
Cited by 33 | Viewed by 9490
Abstract
Salicylic acid (SA) is a plant hormone which plays a crucial role in the plant defense against various pathogens and abiotic stresses. Increasing reports suggest that this phenolic compound and its derivatives, collectively termed salicylates, not only regulate plant defense but also have [...] Read more.
Salicylic acid (SA) is a plant hormone which plays a crucial role in the plant defense against various pathogens and abiotic stresses. Increasing reports suggest that this phenolic compound and its derivatives, collectively termed salicylates, not only regulate plant defense but also have beneficial effects on human health. Both natural and synthetic salicylates are known to have multiple targets in humans, thereby exhibiting various appreciating pharmacological roles, including anti-inflammatory, anticancer, neuroprotective, antidiabetic effects, and so on. The role of some salicylates, such as acetylsalicylic acid (aspirin), 5-aminosalicylic acid (mesalazine), and amorfrutins in human diseases has been well studied in vitro. However, their clinical significance in different diseases is largely unknown. Based on recent studies, five natural salicylates, including amorfrutin, ginkgolic acid, grifolic acid, tetrahydrocannabinolic acid, and cannabidiolic acid, showed potential roles in different challenging human diseases. This review summarizes together some of the recent information on multitarget regulatory activities of these natural salicylates and their pharmacological roles in human health. Full article
(This article belongs to the Special Issue Biological Properties of Secondary Metabolites and Natural Compounds)
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28 pages, 576 KiB  
Review
Advances in Chemistry and Bioactivity of Magnoflorine and Magnoflorine-Containing Extracts
by Estera Okon, Wirginia Kukula-Koch, Agata Jarzab, Marta Halasa, Andrzej Stepulak and Anna Wawruszak
Int. J. Mol. Sci. 2020, 21(4), 1330; https://doi.org/10.3390/ijms21041330 - 16 Feb 2020
Cited by 48 | Viewed by 6663
Abstract
The review collects together some recent information on the identity and pharmacological properties of magnoflorine, a quaternary aporphine alkaloid, that is widely distributed within the representatives of several botanical families like Berberidaceae, Magnoliaceae, Papaveraceae, or Menispermaceae. Several findings published in the scientific publications [...] Read more.
The review collects together some recent information on the identity and pharmacological properties of magnoflorine, a quaternary aporphine alkaloid, that is widely distributed within the representatives of several botanical families like Berberidaceae, Magnoliaceae, Papaveraceae, or Menispermaceae. Several findings published in the scientific publications mention its application in the treatment of a wide spectrum of diseases including inflammatory ones, allergies, hypertension, osteoporosis, bacterial, viral and fungal infections, and some civilization diseases like cancer, obesity, diabetes, dementia, or depression. The pharmacokinetics and perspectives on its introduction to therapeutic strategies will also be discussed. Full article
(This article belongs to the Special Issue Biological Properties of Secondary Metabolites and Natural Compounds)
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