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Pharmaceuticals
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The 20th Anniversary of Pharmaceuticals—Advances in Natural Products
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The 20th Anniversary of Pharmaceuticals—Advances in Natural Products

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 13285

Special Issue Editors

Dr. Daniela De Vita

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Guest Editor
Department of Environmental Biology, Sapienza University of Rome, Rome, Italy
Interests: medicinal plants; alkaloids; phytochemistry; HPLC; LC-MS; antiviral agents; antifungal agents; anticancer agents; Alzheimer’s disease; cholinesterases
Special Issues, Collections and Topics in MDPI journals
Dr. Marianna Carbone

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Guest Editor
National Research Council (CNR) - Institute of Biomolecular Chemistry (ICB), Pozzuoli, Italy
Interests: marine natural compounds; marine ecology; drug discovery; organic chemistry; NMR
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Historically, natural products (NPs) have been used as remedies for many diseases and illnesses. Even today, with their high structural, physicochemical diversity and health benefits, NPs are suitable for use not only as therapeutic agents but also as cosmetics and food. This Special Issue aims to discuss all the new aspects related to NPs with pharmaceutical applications.

The topics of the Special Issue include but are not limited to in vitro and in vivo evaluation of the biological activities, bioavailability, investigation of the mechanisms of action and pharmaceutical formulations of characterized herbal extracts, pure isolated compounds and/or semisynthetic derivatives. Authors are invited to submit original research articles, reviews, and short communications exploring the recent advances in this field.

Dr. Daniela De Vita
Dr. Marianna Carbone
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. Pharmaceuticals is an international peer-reviewed open access monthly 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 2900 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.

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

Published Papers (7 papers)

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Research

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20 pages, 11381 KiB  
Article
Sesquiterpene Coumarins, Chromones, and Acetophenone Derivatives with Selective Cytotoxicities from the Roots of Ferula caspica M. Bieb. (Apiaceae)
by Fadıl Kaan Kuran, Gülsüm Altıparmak Ülbegi, Gülşah Gamze Arcan, Fatma Memnune Eruçar, Şule Nur Karavuş, Pınar Aksoy Sağırlı, Nur Tan and Mahmut Miski
Pharmaceuticals 2024, 17(10), 1254; https://doi.org/10.3390/ph17101254 - 24 Sep 2024
Viewed by 819
Abstract
In search of selective cytotoxic compounds from Ferula species as potential leads for the treatment of various cancer diseases, a bioactivity-guided isolation study was performed on the roots of Ferula caspica M. Bieb. COLO 205 (colon), K-562 (leukemia), and MCF-7 (breast) cancer cell [...] Read more.
In search of selective cytotoxic compounds from Ferula species as potential leads for the treatment of various cancer diseases, a bioactivity-guided isolation study was performed on the roots of Ferula caspica M. Bieb. COLO 205 (colon), K-562 (leukemia), and MCF-7 (breast) cancer cell lines were used to monitor the cytotoxic activity of column fractions and determine the IC50 value of the active compounds. In addition to the seven known (5–11) compounds, four previously unknown compounds: kayserin A (1), kayserin B (2), 8′-epi-kayserin B angelate (3), and 3-epi-ferulin D (4) were isolated from the dichloromethane extract of the roots of F. caspica. Structure elucidation of the isolated compounds was carried out by extensive spectroscopic analyses such as 1D- and 2D-NMR spectroscopy, High-Resolution Mass Spectroscopy (HRMS), IR spectroscopy, and UV spectroscopy. Although all of the isolated compounds showed various degrees of cytotoxic activity on COLO 205, K-562, and MCF-7 cancer cell lines, the most potent compounds were identified in the following order: 1-Hydroxy-1-(1′-farnesyl)-4,6-dihydroxyacetophenone (HFDHAP, 11), 3-epi-ferulin D (3EFD, 4), and 7-desmethylferulin D (7DMFD, 6). The cytotoxic activities of all three compounds were more potent than that of the reference compound cisplatin (Cis) against all tested cancer cell lines. Still, only HFDHAP (11) was more potent than the reference compound doxorubicin (Dox) against the MCF-7 cancer cell line. The mechanism of action of these three compounds was investigated on the COLO 205 cell line. The results indicated that compounds 4, 6, and 11 trigger caspase-3/8/9 activation and suppress the anti-apoptotic protein, Bcl-xL. Molecular docking studies confirmed the interactions of the three cytotoxic molecules with the active site of the Bcl-xL protein. Full article
(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—Advances in Natural Products)
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19 pages, 4491 KiB  
Article
Myrtus communis L. Essential Oil Exhibits Antiviral Activity against Coronaviruses
by Dar-Yin Li, Matthew G. Donadu, Taylor Shue, Georgios Dangas, Antonis Athanasiadis, Shuiyun Lan, Xin Wen, Basem Battah, Stefania Zanetti, Vittorio Mazzarello, Stefan G. Sarafianos, Marco Ferrari and Eleftherios Michailidis
Pharmaceuticals 2024, 17(9), 1189; https://doi.org/10.3390/ph17091189 - 10 Sep 2024
Viewed by 949
Abstract
Human coronaviruses are a continuous threat to the human population and have limited antiviral treatments, and the recent COVID-19 pandemic sparked interest in finding new antiviral strategies, such as natural products, to combat emerging coronaviruses. Rapid efforts in the scientific community to identify [...] Read more.
Human coronaviruses are a continuous threat to the human population and have limited antiviral treatments, and the recent COVID-19 pandemic sparked interest in finding new antiviral strategies, such as natural products, to combat emerging coronaviruses. Rapid efforts in the scientific community to identify effective antiviral agents for coronaviruses remain a focus to minimize mortalities and global setbacks. In this study, an essential oil derived from Myrtus communis L. (MEO) is effective against HCoV-229E and HCoV-OC43 virus infections in comparison to two FDA-approved drugs, Remdesivir and Nirmatrelvir. Gas-chromatography and mass spectrometry were used to identify the chemical composition of MEO. Slight antioxidant activity was observed in MEO, indicating a role in oxidative stress. A dose–response curve measuring the EC50 indicates a high potency against HCoV-229E and HCoV-OC43 virus infections on Huh7.5 cells with low cytotoxicity using a PrestoBlue cell viability assay. Our findings demonstrate that MEO exhibits potent antiviral activity against HCoV-229E and HCoV-OC43 on Huh7.5 cells within a low-cytotoxicity range, but not on SARS-CoV-2. Artificial bacterial chromosome plasmids that expressed SARS-CoV-2 used for replicon—to determine viral replication and viral assembly/egress on HEK293T/17 cells—and virus-like particles on Huh7.5-AT cells—to determine viral entry and assembly/egress—showed no antiviral activity with MEO in comparison to Remdesivir. This study reveals the potential effectiveness of MEO as an alternative natural remedy to treat human coronaviruses and a potential antiviral agent for future coronavirus infections. Full article
(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—Advances in Natural Products)
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24 pages, 7441 KiB  
Article
The Bioactive Compounds of Epimedium and Their Potential Mechanism of Action in Treating Osteoporosis: A Network Pharmacology and Experimental Validation Study
by Huizhong Dong, Fen Tang, Zilu Zhao, Wenxuan Huang, Xiangyang Wan, Zhanying Hong, Ying Liu, Xin Dong and Si Chen
Pharmaceuticals 2024, 17(6), 706; https://doi.org/10.3390/ph17060706 - 29 May 2024
Viewed by 1546
Abstract
Osteoporosis is a global health challenge characterized by bone loss and microstructure deterioration, which urgently requires the development of safer and more effective treatments due to the significant adverse effects and limitations of existing drugs for long-term treatment. Traditional Chinese medicine, like Epimedium [...] Read more.
Osteoporosis is a global health challenge characterized by bone loss and microstructure deterioration, which urgently requires the development of safer and more effective treatments due to the significant adverse effects and limitations of existing drugs for long-term treatment. Traditional Chinese medicine, like Epimedium, offers fewer side effects and has been used to treat osteoporosis, yet its active compounds and pharmacological mechanisms remain unclear. In this study, 65 potential active compounds, 258 potential target proteins, and 488 pathways of Epimedium were identified through network pharmacology analysis. Further network analysis and review of the literature identified six potential active compounds and HIF-1α for subsequent experimental validation. In vitro experiments confirmed that 2″-O-RhamnosylIcariside II is the most effective compound among the six potential active compounds. It can promote osteoblast differentiation, bind with HIF-1α, and inhibit both HIF-1α gene and protein expression, as well as enhance COL1A1 protein expression under hypoxic conditions. In vivo experiments demonstrated its ability to improve bone microstructures and reduce bone loss by decreasing bone marrow adipose tissue, enhancing bone formation, and suppressing HIF-1α protein expression. This study is the first to describe the therapeutic effects of 2-O-RhamnosylIcariside II on osteoporosis, which was done, specifically, through a mechanism that targets and inhibits HIF-1α. This study provides a scientific basis for the clinical application of Epimedium and offers a new candidate drug for the treatment of osteoporosis. Additionally, it provides new evidence supporting HIF-1α as a therapeutic target for osteoporosis. Full article
(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—Advances in Natural Products)
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18 pages, 3949 KiB  
Article
Protective Effects of Dietary Vitamin D3, Turmeric Powder, and Their Combination against Gasoline Intoxication in Rats
by Gulfira A. Yestemirova, Zura B. Yessimsiitova and Michael Danilenko
Pharmaceuticals 2024, 17(5), 619; https://doi.org/10.3390/ph17050619 - 10 May 2024
Viewed by 1379
Abstract
The inhalation of gasoline vapors (GV) is associated with developing various pathologies. Particularly, oil refinery and gas station workers are at a greater risk of developing lung cancer, kidney cancer, bladder cancer, and hematological disorders, including acute myeloid leukemia. Therefore, preventing the harmful [...] Read more.
The inhalation of gasoline vapors (GV) is associated with developing various pathologies. Particularly, oil refinery and gas station workers are at a greater risk of developing lung cancer, kidney cancer, bladder cancer, and hematological disorders, including acute myeloid leukemia. Therefore, preventing the harmful effects of GV and alleviating their consequences appear to be important and timely issues. In this study, we investigated the potential of vitamin D3, turmeric powder, and their combination to ameliorate the toxicity of gasoline fumes in rats. Separate groups of animals fed with a standard rodent diet, with or without the supplementation of vitamin D3 (750 IU/kg body weight) and/or turmeric powder (0.5%, w/w, in food), were untreated or treated with GV (11.5 ± 1.3 cm3/h/m3/day) for 30, 60, or 90 days. Changes in the body weight were monitored weekly. Histological, biochemical, and hematological parameters were determined at the end of each treatment period. While the exposure of rats to GV resulted in a time-dependent reduction in body weight, supplementation with vitamin D3, but not with turmeric root powder or their combination, partially prevented weight loss. Macroscopical and histological analyses showed pronounced time-dependent changes in the organs and tissues of GV-treated rats. These included alveolar wall collapse in the lungs, the destruction of the lobular structure and hepatocytolysis in the liver, the shrinkage and fragmentation of glomeruli in the kidneys, and the disorganization of the lymphoid follicles in the spleen. However, co-treatment with the nutritional supplements tested, especially vitamin D3, noticeably alleviated the above conditions. This was accompanied by a significant improvement in the blood chemistry and hematological parameters. Collectively, our results demonstrate that the harmful effects of environmental exposure to GV can be reduced upon supplementation of vitamin D3. The fact that the protective activity of vitamin D3 alone was higher than that of turmeric root powder or the combined treatment suggests that combinations of these supplements may not always be more beneficial than each agent applied separately. Full article
(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—Advances in Natural Products)
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19 pages, 15454 KiB  
Article
Enhancing Therapeutic Efficacy of Donepezil, an Alzheimer’s Disease Drug, by Diplazium esculentum (Retz.) Sw. and Its Phytochemicals
by Woorawee Inthachat, Boonrat Chantong, Pornsiri Pitchakarn, Chawalit Takoon, Jirarat Karinchai, Uthaiwan Suttisansanee and Piya Temviriyanukul
Pharmaceuticals 2024, 17(3), 341; https://doi.org/10.3390/ph17030341 - 6 Mar 2024
Cited by 1 | Viewed by 1940
Abstract
Alzheimer’s disease (AD) is the most common type of dementia and a significant concern to global public health due to the prevalence of aging populations. Donepezil is one of only a few medications approved for use as an anti-AD agent but all have [...] Read more.
Alzheimer’s disease (AD) is the most common type of dementia and a significant concern to global public health due to the prevalence of aging populations. Donepezil is one of only a few medications approved for use as an anti-AD agent but all have adverse side effects. Reducing the dosage of AD drugs with plant extracts (phytotherapy) while maintaining efficacy is one strategy to minimize adverse side effects. We previously reported the anti-AD properties of an edible fern, Diplazium esculentum (Retz.) Sw. (DE), which inhibited key enzymes involved in AD pathogenesis including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase 1 (BACE-1). This study aimed to determine whether DE exhibited a synergistic effect with donepezil. The enzyme inhibitory assay showed that DE extract and its bioactive compounds, kaempferol, and quercetin, slightly impeded AChE inhibition with donepezil, while DE extract and quercetin showed synergistic or additive effects with donepezil against BChE and BACE-1, respectively. DE extract combined with donepezil also improved eye phenotypes in a Drosophila model of AD by preventing ommatidia atrophia and bristle breakages. Furthermore, the DE extract exhibited no genotoxic activities, as determined by the Ames test. Our data revealed that DE extract showed promise when combined with donepezil during AD treatment by targeting BChE and BACE-1. Full article
(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—Advances in Natural Products)
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16 pages, 712 KiB  
Article
Anti-Coccal Activity and Composition of the Essential Oils and Methanolic Extracts Obtained from Brewing Quality Humulus lupulus L. Hop Pellets
by Bartłomiej Piasecki, Anna Biernasiuk and Agnieszka Ludwiczuk
Pharmaceuticals 2023, 16(8), 1098; https://doi.org/10.3390/ph16081098 - 3 Aug 2023
Cited by 1 | Viewed by 1308
Abstract
This study examined the chemical composition and anti-coccal properties of essential oils and methanolic extracts of six different Humulus lupulus L. varieties from Poland: Iunga, Marynka, Sybilla, Magnum, Tradition and Chinook. The activity of an α-acid-enriched fraction of methanolic extracts was also studied. [...] Read more.
This study examined the chemical composition and anti-coccal properties of essential oils and methanolic extracts of six different Humulus lupulus L. varieties from Poland: Iunga, Marynka, Sybilla, Magnum, Tradition and Chinook. The activity of an α-acid-enriched fraction of methanolic extracts was also studied. The chemical composition of essential oils and extracts was determined by gas chromatography–mass spectrometry (GC/MS) and liquid chromatography–mass spectrometry (LC/MS) techniques. The compounds characteristic to H. lupulus extracts include xanthohumol, α-acids, β-acids, and prenylated flavonoids. Essential oil compositions showed a high prevalence of monoterpene hydrocarbon, myrcene and sesquiterpene hydrocarbons, α-humulene and β-caryophyllene. The antimicrobial activity was investigated against eight human cocci pathogenic strains: Staphylococcus aureus MRSA (ATCC 43300), S. aureus MRSA (29213), S. aureus MSSA (ATCC 29213), S. epidermidis (ATCC 12228), Enterococcus faecalis (ATCC 29212), E. faecalis VRE (ATCC 51299), E. faecium (ATCC 19434) and Micrococcus luteus (ATCC 10240). The lowest minimum inhibitory concentrations (MIC) were obtained for extracts and essential oils from Iunga hop samples. Extracts were significantly more active than essential oils. The most susceptible strain to both essential oils and extracts was M. luteus, whilst the least susceptible was E. faecium. The antimicrobial activity correlated with a high concentration of xanthohumol of active extracts rather than with the content of α-acids. Xanthohumol showed considerable activity against MRSA with an MIC value of 3.9 µg/mL. The activity of the α-acid-enriched fraction was mediocre compared to the results of all extracts. Full article
(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—Advances in Natural Products)
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Review

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20 pages, 521 KiB  
Review
Therapeutic Potential and Mechanisms of Bee Venom Therapy: A Comprehensive Review of Apitoxin Applications and Safety Enhancement Strategies
by Maksymilian Stela, Natalia Cichon, Aleksandra Spławska, Monika Szyposzynska and Michal Bijak
Pharmaceuticals 2024, 17(9), 1211; https://doi.org/10.3390/ph17091211 - 14 Sep 2024
Viewed by 4333
Abstract
Apitoxin therapy (BVT—bee venom therapy) is an emerging complementary treatment utilizing bee venom for various medical conditions. This review explores the potential and therapeutic mechanisms of bee venom, focusing on its chemical composition and the methods for its extraction and purification to enhance [...] Read more.
Apitoxin therapy (BVT—bee venom therapy) is an emerging complementary treatment utilizing bee venom for various medical conditions. This review explores the potential and therapeutic mechanisms of bee venom, focusing on its chemical composition and the methods for its extraction and purification to enhance safety while maintaining bioactivity. Bee venom contains amphipathic peptides such as melittin and apamin, enzymes like phospholipase A2, and bioamines including histamine and catecholamines, contributing to its pleiotropic effects. The therapeutic applications of bee venom span anti-inflammatory, analgesic, antimicrobial, antiviral, neuroprotective, anti-arthritic, and anti-cancer activities. Clinical and laboratory studies have demonstrated its efficacy in treating chronic and autoimmune diseases, pain management, and improving quality of life. The immunogenic properties of bee venom necessitate ongoing research to mitigate allergic reactions, ensuring its safe and effective use in medical practice. This review summarizes the current state of research on bee venom therapy, highlighting its potential benefits and future research directions. Full article
(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—Advances in Natural Products)
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