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Bioactive Phytochemicals in Health and Disease

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (25 May 2020) | Viewed by 102955

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Special Issue Editors

Prof. Dr. Natália Cruz-Martins

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Guest Editor

1. Faculty of Medicine, University of Porto, 4099-002 Porto, Portugal
2. Institute for Research and Innovation in Health (i3S), University of Porto, 4099-002 Porto, Portugal
3. Institute of Research and Advanced Training in Health Sciences and Technologies, CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal
4. TOXRUN - Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, Portugal
Interests: evidence-based medicine; phytochemistry; phytopharmacology; drug discovery; natural products biochemistry; bioactive molecules; functional foods; nutraceuticals
Special Issues, Collections and Topics in MDPI journals

Dr. Célia Fortuna Rodrigues

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Guest Editor

Toxicology Research Unit, Cooperativa de Ensino Superior Politécnico e Universitário—CESPU, Gandra, Portugal
Interests: biofilms; Candida; AMR; fungal infection; polymicrobial biofilms; alternatives to antifungals
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Prof. Dr. Marcello Iriti

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Guest Editor

Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, 20133 Milan, Italy
Interests: essential oils; bioactive phytochemicals; ethnopharmacology; antimicrobial resistance; one health; food security
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Special Issue Information

Dear Colleagues,

Environmental factors, oxidative stress, microbial invasion (e.g., bacteria, fungi, and viruses), aging, and even physiopathological processes stimulate inflammation, which is an important defensive mechanism of the host immune system. However, it is recognized that a long-lasting persistent and excessive inflammatory response is a significant risk factor for developing various chronic inflammatory and infectious diseases.

Nutritional deficiencies, and different nutritional and dietary lifestyles, whether poor or absent of essential nutrients, aside from excess intake, can lead to inflammatory complications and loss of function. Bioactive compounds are non-nutritional components derived from plants, foods, and beverages with a multitude of biological effects. The improvement of analytical techniques has allowed scientific community to state that the regular consumption of bioactive phytochemicals is related to the prevention of numerous pathologies, through mechanisms that involve oxidative stress reduction, gene expression modulation, and even enzymatic activation inhibition.

In this way, and despite the high advances stated in this field, further investigations mechanistically linking disease prevention/treatment with bioactive phytochemicals, but driving from pre-clinical to clinical studies, are still needed. Furthermore, pre-clinical studies focusing on understanding signaling pathways, the molecular and biochemical mechanisms behind the clinical efficacy of bioactive compounds on inflammatory and infectious diseases, preventive and therapeutic modalities, and even novel diagnostic techniques are also of utmost interest.

This Special Issue aims to publish pre-clinical findings and clinical trials in this area. We welcome original studies and review articles exploring the impact of bioactive compounds, both on health and disease.

Potential topics include, but are not limited to, the following:

- Nutraceuticals
- Bioactive compounds
- Phytochemicals
- Immunomodulation
- Infectious diseases
- Oxidative stress
- Resistant microorganisms

Prof. Dr. Natália Martins
Prof. Dr. Marcello Iriti
Dr. Célia Rodrigues
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. Journal of Clinical Medicine 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 2600 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

nutraceuticals
bioactive compounds
phytochemicals
immunomodulation
infectious diseases
oxidative stress
resistant microorganisms

Published Papers (11 papers)

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Editorial

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7 pages, 642 KiB

Open AccessEditorial

Telomeres, DNA Damage and Ageing: Potential Leads from Ayurvedic Rasayana (Anti-Ageing) Drugs

by Rohit Sharma and Natália Martins

J. Clin. Med. 2020, 9(8), 2544; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082544 - 06 Aug 2020

Cited by 36 | Viewed by 9809

Abstract

Ageing, while a relentless, unidirectional and pleiotropic phenomenon of life, is a key trigger for several age-related disorders, such as cancer, cataract, osteoporosis, hypertension, cardiovascular (CV), metabolic and even neurodegenerative ailments, including Alzheimer’s (AD) and Parkinson’s (PD) disease [...] Full article

(This article belongs to the Special Issue Bioactive Phytochemicals in Health and Disease)

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Research

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14 pages, 3026 KiB

Open AccessArticle

Kurarinone Inhibits HCoV-OC43 Infection by Impairing the Virus-Induced Autophagic Flux in MRC-5 Human Lung Cells

by Jung Sun Min, Dong Eon Kim, Young-Hee Jin and Sunoh Kwon

J. Clin. Med. 2020, 9(7), 2230; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9072230 - 14 Jul 2020

Cited by 17 | Viewed by 3392

Abstract

Kurarinone is a prenylated flavonone isolated from the roots of Sophora flavescens. Among its known functions, kurarinone has both anti-apoptotic and anti-inflammatory properties. Coronaviruses (CoVs), including HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2, are the causative agents of respiratory virus infections that range in severity from the common cold to severe pneumonia. There are currently no effective treatments for coronavirus-associated diseases. In this report, we examined the anti-viral impact of kurarinone against infection with the human coronavirus, HCoV-OC43. We found that kurarinone inhibited HCoV-OC43 infection in human lung fibroblast MRC-5 cells in a dose-dependent manner with an IC₅₀ of 3.458 ± 0.101 µM. Kurarinone inhibited the virus-induced cytopathic effect, as well as extracellular and intracellular viral RNA and viral protein expression. Time-of-addition experiments suggested that kurarinone acted at an early stage of virus infection. Finally, we found that HCoV-OC43 infection increased the autophagic flux in MRC-5 cells; kurarinone inhibited viral replication via its capacity to impair the virus-induced autophagic flux. As such, we suggest that kurarinone may be a useful therapeutic for the treatment of diseases associated with coronavirus infection. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals in Health and Disease)

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17 pages, 1497 KiB

Open AccessArticle

Antibacterial Activity of Some Flavonoids and Organic Acids Widely Distributed in Plants

by Artur Adamczak, Marcin Ożarowski and Tomasz M. Karpiński

J. Clin. Med. 2020, 9(1), 109; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9010109 - 31 Dec 2019

Cited by 300 | Viewed by 13348

Abstract

Among natural substances widespread in fruits, vegetables, spices, and medicinal plants, flavonoids and organic acids belong to the promising groups of bioactive compounds with strong antioxidant and anti-inflammatory properties. The aim of the present work was to evaluate the antibacterial activity of 13 common flavonoids (flavones, flavonols, flavanones) and 6 organic acids (aliphatic and aromatic acids). The minimal inhibitory concentrations (MICs) of selected plant substances were determined by the micro-dilution method using clinical strains of four species of pathogenic bacteria. All tested compounds showed antimicrobial properties, but their biological activity was moderate or relatively low. Bacterial growth was most strongly inhibited by salicylic acid (MIC = 250–500 μg/mL). These compounds were generally more active against Gram-negative bacteria: Escherichia coli and Pseudomonas aeruginosa than Gram-positive ones: Enterococcus faecalis and Staphylococcus aureus. An analysis of the antibacterial effect of flavone, chrysin, apigenin, and luteolin showed that the presence of hydroxyl groups in the phenyl rings A and B usually did not influence on the level of their activity. A significant increase in the activity of the hydroxy derivatives of flavone was observed only for S. aureus. Similarly, the presence and position of the sugar group in the flavone glycosides generally had no effect on the MIC values. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals in Health and Disease)

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11 pages, 6001 KiB

Open AccessArticle

Ulmus parvifolia Accelerates Skin Wound Healing by Regulating the Expression of MMPs and TGF-β

by Min Cheol Kang, Silvia Yumnam, Woo Sung Park, Hae Min So, Ki Hyun Kim, Meong Cheol Shin, Mi-Jeong Ahn and Sun Yeou Kim

J. Clin. Med. 2020, 9(1), 59; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9010059 - 26 Dec 2019

Cited by 11 | Viewed by 4073

Abstract

Ulmus parvifolia is one of the medicinal plants used traditionally for treatment of wounds. We intended to investigate the wound healing effect of the powder of Ulmus parvifolia (UP) root bark in a mouse wound healing model. We also determined the mechanisms of effects of U. parvifolia in skin and skin wound healing effects using a keratinocyte model. Animal experiments showed that the wound lesions in the mice decreased with 200 mesh U. parvifolia root bark powder and were significantly reduced with treatment by UP, compared with those treated with Ulmus macrocarpa (UM). Results from in vitro experiments also revealed that UP extract promoted the migration of human skin keratinocytes. UP powder treatment upregulated the expression of the matrix metalloproteinase-2 and -9 protein and significantly increased transforming growth factor (TGF)-β levels. We confirmed that topical administration of the bark powder exerted a significant effect on skin wound healing by upregulating the expression of MMP and transforming growth factor-β. Our study suggests that U. parvifolia may be a potential candidate for skin wound healing including epidermal skin rejuvenation. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals in Health and Disease)

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17 pages, 2241 KiB

Open AccessArticle

Radioprotective and Antimutagenic Effects of Pycnanthus angolensis Warb Seed Extract against Damage Induced by X rays

by Daniel Gyingiri Achel, Miguel Alcaraz-Saura, Julián Castillo, Amparo Olivares and Miguel Alcaraz

J. Clin. Med. 2020, 9(1), 6; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9010006 - 18 Dec 2019

Cited by 9 | Viewed by 2571

Abstract

Although different studies have demonstrated different applications of Pycnanthus angolensis extracts in traditional African and Asian medicine, its possible antimutagenic or genoprotective capacities have never been explored. We studied these capabilities of Pycnanthus angolensis seed extract (PASE) by means of the two micronucleus assays, determining the frequency of micronucleus (MN) yield in mouse bone marrow (in vivo) and in human lymphocytes blocked by cytochalasin B (in vitro). PASE exhibited a significant genoprotective capacity (p < 0.001) against X-rays with a protection factor of 35% in both in vivo and in vitro assays. Further, its radioprotective effects were determined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) cell viability test in two cell lines: one being radiosensitive (i.e., human prostate epithelium (PNT2) cells) and the other being radioresistant (i.e., B16F10 melanoma cells). In the radiosensitive cells, PASE showed a protection factor of 35.5%, thus eliminating 43.8% of X-ray-induced cell death (p < 0.001) and a dose reduction factor of 2.5. In the radioresistant cells, a protection factor of 29% (p < 0.001) with a dose reduction factor of 4 was realized. PASE elicited a greater radioprotective capacity than the substances currently used in radiation oncology and, thus, could be developed as a nutraceutical radioprotectant for workers and patients exposed to ionizing radiation. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals in Health and Disease)

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Review

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45 pages, 6871 KiB

Open AccessReview

Role of Vacha (Acorus calamus Linn.) in Neurological and Metabolic Disorders: Evidence from Ethnopharmacology, Phytochemistry, Pharmacology and Clinical Study

by Vineet Sharma, Rohit Sharma, DevNath Singh Gautam, Kamil Kuca, Eugenie Nepovimova and Natália Martins

J. Clin. Med. 2020, 9(4), 1176; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9041176 - 19 Apr 2020

Cited by 48 | Viewed by 13331

Abstract

Vacha (Acorus calamus Linn. (Acoraceae)) is a traditional Indian medicinal herb, which is practiced to treat a wide range of health ailments, including neurological, gastrointestinal, respiratory, metabolic, kidney, and liver disorders. The purpose of this paper is to provide a comprehensive up-to-date report on its ethnomedicinal use, phytochemistry, and pharmacotherapeutic potential, while identifying potential areas for further research. To date, 145 constituents have been isolated from this herb and identified, including phenylpropanoids, sesquiterpenoids, and monoterpenes. Compelling evidence is suggestive of the biopotential of its various extracts and active constituents in several metabolic and neurological disorders, such as anticonvulsant, antidepressant, antihypertensive, anti-inflammatory, immunomodulatory, neuroprotective, cardioprotective, and anti-obesity effects. The present extensive literature survey is expected to provide insights into the involvement of several signaling pathways and oxidative mechanisms that can mitigate oxidative stress, and other indirect mechanisms modulated by active biomolecules of A. calamus to improve neurological and metabolic disorders. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals in Health and Disease)

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23 pages, 3253 KiB

Open AccessReview

Pharmacological Therapeutics Targeting RNA-Dependent RNA Polymerase, Proteinase and Spike Protein: From Mechanistic Studies to Clinical Trials for COVID-19

by Jiansheng Huang, Wenliang Song, Hui Huang and Quancai Sun

J. Clin. Med. 2020, 9(4), 1131; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9041131 - 15 Apr 2020

Cited by 112 | Viewed by 20642

Abstract

An outbreak of novel coronavirus-related pneumonia COVID-19, that was identified in December 2019, has expanded rapidly, with cases now confirmed in more than 211 countries or areas. This constant transmission of a novel coronavirus and its ability to spread from human to human have prompted scientists to develop new approaches for treatment of COVID-19. A recent study has shown that remdesivir and chloroquine effectively inhibit the replication and infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCov) in vitro. In the United States, one case of COVID-19 was successfully treated with compassionate use of remdesivir in January of 2020. In addition, a clinically proven protease inhibitor, camostat mesylate, has been demonstrated to inhibit Calu-3 infection with SARS-CoV-2 and prevent SARS-2-spike protein (S protein)-mediated entry into primary human lung cells. Here, we systemically discuss the pharmacological therapeutics targeting RNA-dependent RNA polymerase (RdRp), proteinase and S protein for treatment of SARS-CoV-2 infection. This review should shed light on the fundamental rationale behind inhibition of SARS-CoV-2 enzymes RdRp as new therapeutic approaches for management of patients with COVID-19. In addition, we will discuss the viability and challenges in targeting RdRp and proteinase, and application of natural product quinoline and its analog chloroquine for treatment of coronavirus infection. Finally, determining the structural-functional relationships of the S protein of SARS-CoV-2 will provide new insights into inhibition of interactions between S protein and angiotensin-converting enzyme 2 (ACE2) and enable us to develop novel therapeutic approaches for novel coronavirus SARS-CoV-2. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals in Health and Disease)

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25 pages, 1584 KiB

Open AccessReview

Therapeutic Applications of Curcumin Nanomedicine Formulations in Cardiovascular Diseases

by Bahare Salehi, María L. Del Prado-Audelo, Hernán Cortés, Gerardo Leyva-Gómez, Zorica Stojanović-Radić, Yengkhom Disco Singh, Jayanta Kumar Patra, Gitishree Das, Natália Martins, Miquel Martorell, Marzieh Sharifi-Rad, William C. Cho and Javad Sharifi-Rad

J. Clin. Med. 2020, 9(3), 746; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9030746 - 10 Mar 2020

Cited by 57 | Viewed by 11207

Abstract

Cardiovascular diseases (CVD) compromises a group of heart and blood vessels disorders with high impact on human health and wellbeing. Curcumin (CUR) have demonstrated beneficial effects on these group of diseases that represent a global burden with a prevalence that continues increasing progressively. Pre- and clinical studies have demonstrated the CUR effects in CVD through its anti-hypercholesterolemic and anti-atherosclerotic effects and its protective properties against cardiac ischemia and reperfusion. However, the CUR therapeutic limitation is its bioavailability. New CUR nanomedicine formulations are developed to solve this problem. The present article aims to discuss different studies and approaches looking into the promising role of nanotechnology-based drug delivery systems to deliver CUR and its derivatives in CVD treatment, with an emphasis on their formulation properties, experimental evidence, bioactivity, as well as challenges and opportunities in developing these systems. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals in Health and Disease)

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28 pages, 1321 KiB

Open AccessReview

Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence

by Jadwiga Jodynis-Liebert and Małgorzata Kujawska

J. Clin. Med. 2020, 9(3), 718; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9030718 - 06 Mar 2020

Cited by 61 | Viewed by 6314

Abstract

Many phytochemicals demonstrate nonmonotonic dose/concentration-response termed biphasic dose-response and are considered to be hormetic compounds, i.e., they induce biologically opposite effects at different doses. In numerous articles the hormetic nature of phytochemicals is declared, however, no experimental evidence is provided. Our aim was to present the overview of the reports in which phytochemical-induced biphasic dose-response is experimentally proven. Hence, we included in the current review only articles in which the reversal of response between low and high doses/concentrations of phytochemicals for a single endpoint was documented. The majority of data on biphasic dose-response have been found for phytoestrogens; other reports described these types of effects for resveratrol, sulforaphane, and natural compounds from various chemical classes such as isoquinoline alkaloid berberine, polyacetylenes falcarinol and falcarindiol, prenylated pterocarpan glyceollin1, naphthoquinones plumbagin and naphazarin, and panaxatriol saponins. The prevailing part of the studies presented in the current review was performed on cell cultures. The most common endpoint tested was a proliferation of tumor and non-cancerous cells. Very few experiments demonstrating biphasic dose-response induced by phytochemicals were carried out on animal models. Data on the biphasic dose-response of various endpoints to phytochemicals may have a potential therapeutic or preventive implication. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals in Health and Disease)

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35 pages, 4459 KiB

Open AccessReview

Curcumin’s Nanomedicine Formulations for Therapeutic Application in Neurological Diseases

by Bahare Salehi, Daniela Calina, Anca Oana Docea, Niranjan Koirala, Sushant Aryal, Domenico Lombardo, Luigi Pasqua, Yasaman Taheri, Carla Marina Salgado Castillo, Miquel Martorell, Natália Martins, Marcello Iriti, Hafiz Ansar Rasul Suleria and Javad Sharifi-Rad

J. Clin. Med. 2020, 9(2), 430; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9020430 - 05 Feb 2020

Cited by 120 | Viewed by 9848

Abstract

The brain is the body’s control center, so when a disease affects it, the outcomes are devastating. Alzheimer’s and Parkinson’s disease, and multiple sclerosis are brain diseases that cause a large number of human deaths worldwide. Curcumin has demonstrated beneficial effects on brain health through several mechanisms such as antioxidant, amyloid β-binding, anti-inflammatory, tau inhibition, metal chelation, neurogenesis activity, and synaptogenesis promotion. The therapeutic limitation of curcumin is its bioavailability, and to address this problem, new nanoformulations are being developed. The present review aims to summarize the general bioactivity of curcumin in neurological disorders, how functional molecules are extracted, and the different types of nanoformulations available. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals in Health and Disease)

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23 pages, 2429 KiB

Open AccessReview

Potential Therapeutic Targets of Quercetin and Its Derivatives: Its Role in the Therapy of Cognitive Impairment

by Md. Jakaria, Shofiul Azam, Song-Hee Jo, In-Su Kim, Raju Dash and Dong-Kug Choi

J. Clin. Med. 2019, 8(11), 1789; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm8111789 - 25 Oct 2019

Cited by 34 | Viewed by 7029

Abstract

Quercetin (QC) is a flavonoid and crucial bioactive compound found in a variety of vegetables and fruits. In preclinical studies, QC has demonstrated broad activity against several diseases and disorders. According to recent investigations, QC is a potential therapeutic candidate for the treatment of nervous system illnesses because of its protective role against oxidative damage and neuroinflammation. QC acts on several molecular signals, including ion channels, neuroreceptors, and inflammatory receptor signaling, and it also regulates neurotrophic and anti-oxidative signaling molecules. While the study of QC in neurological disorders has focused on numerous target molecules, the role of QC on certain molecular targets such as G-protein coupled and nuclear receptors remains to be investigated. Our analysis presents several molecular targets of QC and its derivatives that demonstrate the pharmacological potential against cognitive impairment. Consequently, this article may guide future studies using QC and its analogs on specific signaling molecules. Finding new molecular targets of QC and its analogs may ultimately assist in the treatment of cognitive impairment. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals in Health and Disease)

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