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Pharmaceuticals
Special Issues
Bioactive Compounds Derived from Plants and Their Medicinal Potential
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Bioactive Compounds Derived from Plants and Their Medicinal Potential

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

Deadline for manuscript submissions: 5 October 2024 | Viewed by 4388

Special Issue Editors

Dr. Maria de Lourdes Pereira

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Guest Editor
CICECO-Aveiro Institute of Materials and Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal
Interests: chromium compounds; food supplements; obesogenic; natural compounds
Special Issues, Collections and Topics in MDPI journals
Dr. Veeranoot Nissapatorn

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Guest Editor
School of Allied Health Sciences, Southeast Asia Water Team, World Union for Herbal Drug Discovery, and Research Excellence Center for Innovation and Health Products, Walailak University, Nakhon Si Thammarat, Thailand
Interests: parasitology; waterborne parasites; tropical diseases; Acanthamoeba; infectious disease epidemiology; natural products
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ana Paula Girol

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Guest Editor
Pro-Rector of Research and Post-Graduation UNIFIPA, Catanduva, SP, Brazil
Interests: herbal medicines and biomaterials in inflammatory and tumor processes; mast cells; annexin A1 protein
Special Issues, Collections and Topics in MDPI journals
Dr. Sónia M. R. Oliveira

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Guest Editor
Faculty of Dental Medicine, Catholic University of Portugal, 3504-505 Viseu, Portugal
Interests: neurophysiology; cancer biology; reproductive biology; cellular biology; biomimetic systems; rare diseases; eHealth; histology; molecular biology; biomedicine; infections; public health
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Medicinal plants offer a rich source of pharmaceutical compounds with demonstrated potential to improve and address human and animal diseases, offering important avenues for drug discovery. These bioactive compounds have diverse properties, such as antimicrobial, larvicidal, antioxidant, anticancer, and immunomodulatory activities. Advancements in experimental methodologies, ranging from experimental models and culture systems to microfluidic platforms, have facilitated the study of the bioactivity and pharmacology of these compounds with greater precision and efficiency.

As there have been advances in different technologies, such as data science and machine learning, that have begun to transform evidence-based medicine, particularly at the diagnostics level, we gain a ‘glimpse’ of what next-generation medicine and pharmacy can offer. Despite these advances, in both basic science and technology, clinical translations remain scarce or lagging.

This Special Issue aims to comprehensively gather reports on the bioactivity of several medicinal plants through rigorous experimentation (e.g., in vitro, ex vivo, and in vivo) and advance the development of evidence-based pharmaceutical interventions. The reports can explore various aspects of natural product pharmacology, including the identification of novel compounds, mechanistic studies, synergistic effects, formulation development, and clinical trials. In this collection, we would like to promote some positive paradigm shifts towards more natural and patient-centric therapeutics. Original research and review articles are welcome.

Dr. Maria de Lourdes Pereira
Dr. Veeranoot Nissapatorn
Prof. Dr. Ana Paula Girol
Dr. Sónia M. R. Oliveira
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.

Keywords

  • phytopharmaceutical drugs
  • activity screening (antimicrobial, antioxidant, anticancer, and immunomodulatory activity)
  • experimental models (in vitro, ex vivo, in vivo, etc.)
  • microfluidic systems

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Published Papers (7 papers)

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Research

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19 pages, 4126 KiB  
Article
Thymol Protects against 5-Fluorouracil-Induced Hepatotoxicity via the Regulation of the Akt/GSK-3β Pathway in In Vivo and In Silico Experimental Models
by Yasmen F. Mahran, Amira M. Badr, Layla A. Al-Kharashi, Hanaa N. Alajami, Nouf T. Aldamry, Nervana Moustafa Bayoumy, Elshaymaa I. Elmongy and Sahar Soliman
Pharmaceuticals 2024, 17(8), 1094; https://doi.org/10.3390/ph17081094 - 21 Aug 2024
Viewed by 459
Abstract
Background: 5-fluorouracil (5-FU) is a widely used, highly effective chemotherapeutic agent. However, its therapeutic efficacy is often limited by associated adverse effects, with hepatotoxicity being frequently reported with 5-FU therapy. Thymol is a monoterpene found in thyme (Thymus vulgaris L., Lamiaceae) and [...] Read more.
Background: 5-fluorouracil (5-FU) is a widely used, highly effective chemotherapeutic agent. However, its therapeutic efficacy is often limited by associated adverse effects, with hepatotoxicity being frequently reported with 5-FU therapy. Thymol is a monoterpene found in thyme (Thymus vulgaris L., Lamiaceae) and is known for its antioxidant, anti-apoptotic, and anticancer activities. This study aimed to explore the hepatoprotective activity of thymol against 5-FU-induced liver injury. Methods: Rats received two intraperitoneal doses of 5-FU (150 mg/kg) either alone or in combination with thymol at doses of 60 mg/kg or 120 mg/kg. Liver enzymes, oxidative stress, and apoptotic markers, in addition to histopathological changes, were assessed. Results: 5-FU induced marked liver injuries as evidenced by elevated liver enzymes and histopathological changes, in addition to abnormalities of oxidative and apoptotic markers. The administration of thymol ameliorated the 5-FU-induced oxidative damage through increasing hepatic antioxidants and lowering lipid peroxidation. Apoptotic response markers such as Bax, Bcl-2, Bax/Bcl-2 ratio, and PARP were also improved. Furthermore, Western blotting analysis showed that thymol modulated the 5-FU-induced changes in the expression of Akt/GSK-3β and p44/42 MAPK (ERK1/2) signaling pathways. Conclusions: Our research is the first to shed light on thymol’s potential protective effect against 5-FU- induced hepatotoxicity by inhibiting oxidative and apoptotic pathways and modulating the Akt/ GSK-3β as well as p44/42 MAPK (ERK1/2) signaling pathways. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)
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22 pages, 3434 KiB  
Article
Antinociceptive and Anti-Inflammatory Activities of Acetonic Extract from Bougainvillea x buttiana (var. Rose)
by Gabriela Castañeda-Corral, Mayra Cedillo-Cortezano, Magdalena Aviles-Flores, Misael López-Castillo, Juan José Acevedo-Fernández and Vera L. Petricevich
Pharmaceuticals 2024, 17(8), 1037; https://doi.org/10.3390/ph17081037 - 6 Aug 2024
Viewed by 712
Abstract
Background:Bougainvillea x buttiana is an ornamental plant with antioxidant, anti-inflammatory, and cytotoxic activities, which has been traditionally used to treat respiratory diseases. This study aimed to investigate whether the acetonic extract of Bougainvillea x buttiana var. Rose (BxbRAE-100%) has analgesic and anti-inflammatory [...] Read more.
Background:Bougainvillea x buttiana is an ornamental plant with antioxidant, anti-inflammatory, and cytotoxic activities, which has been traditionally used to treat respiratory diseases. This study aimed to investigate whether the acetonic extract of Bougainvillea x buttiana var. Rose (BxbRAE-100%) has analgesic and anti-inflammatory properties and its potential action mechanisms. Methods: Analgesic and anti-inflammatory activities were evaluated using three murine pain models and two acute inflammation models. In vitro, the ability of the extract to inhibit proteolytic activity and the activities of the enzymes phospholipase A2 (PLA2) and cyclooxygenase (COX) were evaluated. In silico analysis was performed to predict the physicochemical and Absorption, distribution, metabolism, and excretion (ADME) profiles of the compounds previously identified in BxbRAE-100%. Results: In vivo BxbRAE-100% decreased the nociceptive behaviors in the writhing model, the tail immersion, and the formalin test, suggesting that the extract has the potential to relieve pain at peripheral and central levels. Additionally, topical or oral BxbRAE-100% treatment reduced dose-dependent 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation and carrageenan-induced paw edema, respectively. In vitro, BxbRAE-100% significantly inhibited proteolytic activity and PLA2, COX-1 and COX-2 activities. In silico, the compounds previously identified in BxbRAE-100% met Lipinski’s rule of five and showed adequate ADME properties. Conclusions: These results support the use of B. x buttiana in Traditional Mexican Medicine and highlight its potential for the development of new treatments for pain and inflammation. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)
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19 pages, 11500 KiB  
Article
Ethanolic Extracts of Cupressaceae Species Conifers Provide Rapid Protection against Barium Chloride-Induced Cardiac Arrhythmia
by Meng-Ting Zeng, Li-Yue Huang, Xiao-Hui Zheng, Yan-Qi Fu and Ching-Feng Weng
Pharmaceuticals 2024, 17(8), 1003; https://doi.org/10.3390/ph17081003 - 29 Jul 2024
Viewed by 550
Abstract
Sudden cardiac death (SCD) is responsible for a high percentage of cardiovascular fatalities, with ventricular arrhythmias being the most common cause. Despite numerous clinically available antiarrhythmic drugs (AADs), AADs retain some undesirable arrhythmic effects, and their inappropriate use can lead to severe adverse [...] Read more.
Sudden cardiac death (SCD) is responsible for a high percentage of cardiovascular fatalities, with ventricular arrhythmias being the most common cause. Despite numerous clinically available antiarrhythmic drugs (AADs), AADs retain some undesirable arrhythmic effects, and their inappropriate use can lead to severe adverse reactions. The exploration of new therapeutic options against arrhythmias with fewer unreceptive effects is of utmost importance. The ethanolic extracts of seven Cupressaceae species, namely, Chamaecyparis obtusa, Juniperus chinensis (L.) Ant., Sabina chinensis (L.) Ant. cv. Kaizuca, Platycladus orientalis (L.) Franco, Juniperus sabina L., Fokienia hodginsii, and Juniperus chinensis ‘Pyramidalis’ were investigated for their pharmacological effects on barium chloride (BaCl2)-induced arrhythmia using normal II lead electrocardiogram (ECG) measurements in a mouse model. According to the ECG profiles, pretreatment with C. obtusa, P. orientalis, and J. sabina extracts provoked dose-dependent protection against BaCl2-induced arrhythmia, while pretreatment with the other four species and amiodarone did not exert cardioprotective effects. The treatment effects were confirmed using a rat model. The therapeutic effects of C. obtusa, P. orientalis, and J. sabina extracts on the M2 and M3 receptors but not the M1 receptor were mediated by the inhibition of the M2 receptor blocker (methoctramine tetrahydrochloride), M3 antagonist (4-DAMP), or M1 receptor blocker (pirenzepine dihydrochloride). This first-line evidence illustrates that certain Cupressaceae species possess active antiarrhythmic components. The first line of key findings revealed that active components of certain Cupressaceae species have cardioprotective effects, suggesting that these innovative phytochemicals have promising potential for preventing the occurrence of cardiac arrhythmia and reducing sudden cardiac death. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)
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22 pages, 7552 KiB  
Article
Evaluation of Crocetin as a Protective Agent in High Altitude Hypoxia-Induced Organ Damage
by Jun Yang, Kai Luo, Ziliang Guo, Renjie Wang, Qingyuan Qian, Shuhe Ma, Maoxing Li and Yue Gao
Pharmaceuticals 2024, 17(8), 985; https://doi.org/10.3390/ph17080985 - 25 Jul 2024
Viewed by 537
Abstract
Crocetin is an aglycone of crocin naturally occurring in saffron and has been proved to have antioxidant, anti-inflammatory, and antibacterial activities. In this experiment, the protective effect of crocetin on vital organs in high-altitude hypoxia rats was studied. Crocetin was prepared from gardenia [...] Read more.
Crocetin is an aglycone of crocin naturally occurring in saffron and has been proved to have antioxidant, anti-inflammatory, and antibacterial activities. In this experiment, the protective effect of crocetin on vital organs in high-altitude hypoxia rats was studied. Crocetin was prepared from gardenia by the alkaline hydrolysis method, and its reducing ability and free radical scavenging ability were tested. The in vitro anti-hypoxia vitality was studied on PC12 cells. The anti-hypoxic survival time of mice was determined in several models. The acute hypoxic injury rat model was established by simulating the hypoxic environment of 8000 m-high altitude for 24 h, and the anti-hypoxia effect of crocetin was evaluated by intraperitoneal injection with the doses of 10, 20, and 40 mg/kg. The water contents of the brain and lung were determined, and the pathological sections in the brain, lung, heart, liver, and kidney were observed by HE staining. The levels of oxidative stress (SOD, CAT, H2O2, GSH, GSH-Px, MDA) and inflammatory factors (IL-1β, IL-6, TNF-α, VEGF) in rat brain, lung, heart, liver, and kidney tissues were detected by ELISA. The results indicated that crocetin exhibited strong reducing ability and free radical scavenging ability and could improve the activity of PC12 cells under hypoxia. After intraperitoneal injection with crocetin, the survival time of mice was prolonged, and the pathological damage, oxidative stress, and inflammation in rats’ tissue were ameliorated. The protective activity of crocetin on vital organs in high-altitude hypoxia rats may be related to reducing oxidative stress and inhibiting inflammatory response. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)
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Review

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21 pages, 1438 KiB  
Review
Exploring the Comprehensive Neuroprotective and Anticancer Potential of Afzelin
by Mateusz Kciuk, Nitika Garg, Sanchit Dhankhar, Monika Saini, Somdutt Mujwar, Sushma Devi, Samrat Chauhan, Thakur Gurjeet Singh, Randhir Singh, Beata Marciniak, Adrianna Gielecińska and Renata Kontek
Pharmaceuticals 2024, 17(6), 701; https://doi.org/10.3390/ph17060701 - 28 May 2024
Viewed by 987
Abstract
Neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and others) and cancer, seemingly disparate in their etiology and manifestation, exhibit intriguing associations in certain cellular and molecular processes. Both cancer and neurodegenerative diseases involve the deregulation of cellular processes such as apoptosis, proliferation, [...] Read more.
Neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and others) and cancer, seemingly disparate in their etiology and manifestation, exhibit intriguing associations in certain cellular and molecular processes. Both cancer and neurodegenerative diseases involve the deregulation of cellular processes such as apoptosis, proliferation, and DNA repair and pose a significant global health challenge. Afzelin (kaempferol 3-O-rhamnoside) is a flavonoid compound abundant in various plant sources. Afzelin exhibits a diverse range of biological activities, offering promising prospects for the treatment of diseases hallmarked by oxidative stress and deregulation of cell death pathways. Its protective potential against oxidative stress is also promising for alleviating the side effects of chemotherapy. This review explores the potential therapeutic implications of afzelin, including its capacity to mitigate oxidative stress, modulate inflammation, and promote cellular regeneration in neurodegenerative and cancer diseases. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)
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Other

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15 pages, 2873 KiB  
Systematic Review
Unveiling the Neuroprotective Potential of Date Palm (Phoenix dactylifera): A Systematic Review
by Syed Mohammed Basheeruddin Asdaq, Abdulaziz Ali Almutiri, Abdullah Alenzi, Maheen Shaikh, Mujeeb Ahmed Shaik, Sultan Alshehri and Syed Imam Rabbani
Pharmaceuticals 2024, 17(9), 1221; https://doi.org/10.3390/ph17091221 (registering DOI) - 17 Sep 2024
Abstract
Background: Neurodegenerative diseases primarily afflict the elderly and are characterized by a progressive loss of neurons. Oxidative stress is intricately linked to the advancement of these conditions. This study focuses on Phoenix dactylifera (P. dactylifera; Family: Arecaceae), commonly known as “Ajwa,” [...] Read more.
Background: Neurodegenerative diseases primarily afflict the elderly and are characterized by a progressive loss of neurons. Oxidative stress is intricately linked to the advancement of these conditions. This study focuses on Phoenix dactylifera (P. dactylifera; Family: Arecaceae), commonly known as “Ajwa,” a globally cultivated herbal plant renowned for its potent antioxidant properties and reported neuroprotective effects in pharmacological studies. Method: This comprehensive systematic review delves into the antioxidant properties of plant extracts and their phytochemical components, with a particular emphasis on P. dactylifera and its potential neuroprotective benefits. Preferred reporting items for systemic reviews and meta-analysis (PRISMA) were employed to review the articles. Results: The study includes 269 articles published in the literature and 17 were selected after qualitative analysis. The growing body of research underscores the critical role of polyphenolic compounds found in P. dactylifera, which significantly contribute to its neuroprotective effects through antioxidant mechanisms. Despite emerging insights into the antioxidant actions of P. dactylifera, further investigation is essential to fully elucidate the specific pathways through which it confers neuroprotection. Conclusions: Like many other plant-based supplements, P. dactylifera’s antioxidant effects are likely mediated by synergistic interactions among its diverse bioactive compounds, rather than by any single constituent alone. Therefore, additional preclinical and clinical studies are necessary to explore P. dactylifera’s therapeutic potential comprehensively, especially in terms of its targeted antioxidant activities aimed at mitigating neurodegenerative processes. Such research holds promise for advancing our understanding and potentially harnessing the therapeutic benefits of P. dactylifera in neuroprotection. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)
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8 pages, 648 KiB  
Brief Report
In Vitro Evaluation of the Combinatorial Effect of Naringenin and Miltefosine against Leishmania amazonensis
by Vinícius Lopes Lessa, Gustavo Gonçalves, Beatriz Santos, Victoria Cruz Cavalari, Rafael Felipe da Costa Vieira and Fabiano Borges Figueiredo
Pharmaceuticals 2024, 17(8), 1014; https://doi.org/10.3390/ph17081014 - 1 Aug 2024
Viewed by 484
Abstract
Leishmania amazonensis causes a clinical form called diffuse cutaneous leishmaniasis (DCL) with challenges to treatment, like low efficiency and drug toxicity. Therefore, it is necessary to investigate new therapies using less toxic leishmanicidal compounds, such as flavonoids like naringenin, and their combination with [...] Read more.
Leishmania amazonensis causes a clinical form called diffuse cutaneous leishmaniasis (DCL) with challenges to treatment, like low efficiency and drug toxicity. Therefore, it is necessary to investigate new therapies using less toxic leishmanicidal compounds, such as flavonoids like naringenin, and their combination with conventional drugs, such as miltefosine. Antileishmanial dose/response activity, isobologram, calculation of dose reduction index (DRI), and fractional inhibitory concentration index (FICI) tests were performed on in vitro assays using reference promastigote forms of L. amazonensis (IFLA/BR/67/PH8) to assess the combinatorial effect between naringenin and miltefosine. The in vitro results of isobologram, DRI, and FICI calculations showed that the combination of the compounds had an additive effect and was able to reduce the half maximal inhibitory concentration (IC50) of miltefosine in the promastigote forms of the parasite compared to the treatment of the drug alone. This study demonstrated in vitro the viability of a combination action of the flavonoid with the treatment with miltefosine, opening space for further investigations on the association of natural compounds with the drugs used for the treatment of L. amazonensis. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)
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