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Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2024

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

Deadline for manuscript submissions: 15 December 2024 | Viewed by 11973

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Dr. Dejan Stojković

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Mycological Laboratory, Department of Plant Physiology, Institute for Biological Research "Siniša Stanković"—National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia
Interests: mushrooms; mycomedicines; mycofood
Special Issues, Collections and Topics in MDPI journals

Dr. Marina Soković

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Mycological Laboratory, Department of Plant Physiology, Institute for Biological Research "Siniša Stanković"—National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia
Interests: microfungi; macrofungi; antibacterial activity; antifungal activity; natural products
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Medicinal plants present a valuable source of chemicals with potential therapeutic properties. They are widely used in traditional medicine as supportive therapeutics for various conditions and diseases. In recent years, there have been extensive studies in the area of medicinal plant research dealing with their various pharmacological effects. Novel research on this subject is necessary, since this is an emerging and a rather interesting domain. Many in vitro studies describe the beneficial effects of plants for human health, highlighting promising pharmacological effects.

This Special Issue will cover the biological activity of medicinal plants and isolated compounds. Screening natural preparations for their biological activities is of prime importance, since natural raw material presents an excellent source of pharmaceuticals with a wide variety of different biologically active chemical structures. If your manuscript addresses plant mixtures, please do check the following:

https://www.mdpi.com/journal/pharmaceuticals/instructions#mixtures

The scope of this Special Issue includes, but is not limited to, the following:

Chemical characterization of natural preparations;
Therapeutic potential of natural matrices in cardiovascular diseases, diabetes, cancer, and neurodegenerative diseases;
Antimicrobial activity;
Antioxidant activity;
Anti-enzymatic activity;
Anti-inflammatory activity;
Mechanism of pharmacological actions;
Structure–activity studies.

Dr. Dejan Stojković
Dr. Marina Soković
Guest Editors

Manuscript Submission Information

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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.

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Published Papers (9 papers)

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Research

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20 pages, 3880 KiB

Open AccessArticle

Zingiber officinale Uncovered: Integrating Experimental and Computational Approaches to Antibacterial and Phytochemical Profiling

by Abdel Moneim Elhadi Sulieman, Safa Mustafa Ibrahim, Mamdouh Alshammari, Fahad Abdulaziz, Hajo Idriss, Naimah Asid H. Alanazi, Emad M. Abdallah, Arif Jamal Siddiqui, Sohair A. M. Shommo, Arshad Jamal and Riadh Badraoui

Pharmaceuticals 2024, 17(11), 1551; https://doi.org/10.3390/ph17111551 - 19 Nov 2024

Viewed by 625

Abstract

Background: Zingiber officinale rhizome is widely cultivated in the central region of Sudan (Gezira) and data on the biological properties of this variety grown in Sudan’s climate are scarce. This study aims to comprehensively analyze the antibacterial, antioxidant, phytochemical, and GC-MS properties of Zingiber officinale (ginger rhizome) to explore its potential applications. Methods and Results: The in vitro antibacterial assessment of the aqueous extract of Sudanese ginger revealed moderate activity against Staphylococcus aureus, Salmonella typhi, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumonia, as determined by the disc diffusion method. The inhibition zones ranged from 12.87 ± 0.11 mm to 14.5 ± 0.12 mm at 30 µg/disc. The minimum inhibitory concentration ranged from 6.25 to 25 µg/mL, while the MBC ranged from 25 to 50 µg/mL. The MBC/MIC exhibited a bactericidal effect against all tested bacteria. Phytochemical screening revealed the presence of various chemical constituents, such as saponins, flavonoids, glycosides, alkaloids, steroids, terpenoids, and the absence of tannins in Sudanese ginger rhizome. Furthermore, GC-MS analysis of ginger rhizome identified 22 chemical compounds with retention times ranging from 7.564 to 17.023 min. The identification of 22 chemical compounds through GC-MS analysis further underscores the prospect of harnessing ginger rhizome for the development of novel medications. Computational analyses showed that ginger compounds bind the Protein Data Bank (PDB) codes 1JIJ and 2QZW with high binding affinities, reaching −9.5 kcal/mol. Ginger compounds also established promising molecular interactions with some key residues, satisfactorily explaining the in vitro results and supporting the pharmacokinetic and experimental findings. Conclusions: This study lays the groundwork for future research and pharmaceutical exploration aimed at harnessing the beneficial properties of ginger rhizome for medicinal and therapeutic purposes, particularly its antimicrobial potential. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2024)

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24 pages, 2119 KiB

Open AccessArticle

Comparative Chemical Analysis and Bioactive Properties of Aqueous and Glucan-Rich Extracts of Three Widely Appreciated Mushrooms: Agaricus bisporus (J.E.Lange) Imbach, Laetiporus sulphureus (Bull.) Murill and Agrocybe aegerita (V. Brig.) Vizzini

by Jovana Petrović, Jasmina Glamočlija, Danijel D. Milinčić, Ana Doroški, Steva Lević, Slađana P. Stanojević, Aleksandar Ž. Kostić, Dušanka A. Popović Minić, Bojana B. Vidović, Ana Plećić, Viktor A. Nedović, Mirjana B. Pešić and Dejan Stojković

Pharmaceuticals 2024, 17(9), 1153; https://doi.org/10.3390/ph17091153 - 31 Aug 2024

Viewed by 1130

Abstract

Herein we describe the antioxidant, antimicrobial, antibiofilm, anti-inflammatory and wound-healing potential of aqueous and polysaccharide extracts from three widely appreciated mushrooms: Agrocybe aegerita, Laetiporus sulphureus and Agaricus bisporus. Moreover, we present their detailed phenolic, polysaccharide and protein profiles and ATR-FTIR spectra. The study found that polysaccharide extracts (PEs) from mushrooms had higher total and β-glucan levels than aqueous extracts (AEs), with A. aegerita showing the highest content. L. sulphureus had a higher total protein content, and A. aegerita AE had the highest phenolic content. Our results indicate that all the tested extracts have high potential regarding their bioactive properties, with A. aegerita being the most promising one. Namely, the antibacterial activity assay showed that the development of the skin-infection-causing agent, Staphylococcus aureus, was inhibited with a minimal inhibitory concentration of 4.00 mg/mL and minimal bactericidal concentration of 8.00 mg/mL, while the results regarding wound healing showed that, over the course of 24 h, the A. aegerita extract actively promoted wound closure in the HaCaT keratinocyte cell line model. The anti-inflammatory activity results clearly showed that when we used S. aureus as an inflammation-inducing agent and the A. aegerita aqueous extract in treatment, IL-6 levels reduced to the level of 4.56 pg/mL. The obtained data suggest that the tested mushroom extracts may serve as a source of bioactive compounds, with potential applications in the cosmeceutical, pharmaceutical and food industries. Furthermore, potential skin preparations carefully crafted with mushroom extract may help restore the skin’s barrier function, decrease the probability of staph infections and minimize skin irritation. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2024)

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21 pages, 4607 KiB

Open AccessArticle

Formulation of a Three-Component Essential Oil Mixture from Lavandula dentata, Rosmarinus officinalis, and Myrtus communis for Improved Antioxidant Activity

by Amine Elbouzidi, Mohamed Taibi, Naoufal El Hachlafi, Mounir Haddou, Mohamed Jeddi, Abdellah Baraich, Aya Aouraghe, Reda Bellaouchi, Ramzi A. Mothana, Mohammed F. Hawwal, François Mesnard, Christophe Hano, Abdeslam Asehraou, Khalid Chaabane, Bouchra El Guerrouj and Mohamed Addi

Pharmaceuticals 2024, 17(8), 1071; https://doi.org/10.3390/ph17081071 - 15 Aug 2024

Cited by 1 | Viewed by 1129

Abstract

The optimization of existing natural antioxidants that are highly effective is crucial for advancements in medicine and the food industry. Due to growing concerns regarding the safety of synthetic antioxidants, researchers are increasingly focusing on natural sources, particularly essential oils (EOs). Combining EOs might enhance antioxidant activity due to increased chemical diversity. This study investigates, for the first time, the antioxidant properties of EOs from Lavandula dentata, Rosmarinus officinalis, and Myrtus communis, both individually and in combination, using the augmented-simplex design methodology. The in vitro evaluation of the antioxidant activity was performed using DPPH and ABTS radical scavenging assays. Chromatography gas-mass spectrometry (CG-MS) revealed that 1,8-cineol (37.27%) and pinocarveol (12.67%) are the primary components of L. dentata; verbenone (16.90%), camphor (15.00%), and camphene (11.03%) are predominant in R. officinalis; while cineol (43.32%) is the main component of M. communis. The EOs showed varying scavenging activities against ABTS and DPPH radicals, with DPPH assay values ranging from 194.10 ± 3.01 to 541.19 ± 3.72 µg/mL and ABTS assay values ranging from 134.07 ± 1.70 to 663.42 ± 2.99 µg/mL. These activities were enhanced when the EOs were combined. The optimal antioxidant blend for DPPH_IC50 consisted of 20% L. dentata, 50% R. officinalis, and 30% M. communis. For the highest ABTS radical scavenging activity, the best combination was 18% L. dentata, 43% R. officinalis, and 40% M. communis. These results highlight the potential of EO combinations as new natural formulations for use in cosmeceutical, food, and pharmaceutical sectors. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2024)

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12 pages, 5159 KiB

Open AccessArticle

Ixeris polycephala Extract Alleviates Progression of Benign Prostatic Hyperplasia via Modification of Proliferation, Apoptosis, and Inflammation

by Eun-Bok Baek, Youn-Hwan Hwang, Eun-Ju Hong, Young-Suk Won and Hyo-Jung Kwun

Pharmaceuticals 2024, 17(8), 1032; https://doi.org/10.3390/ph17081032 - 5 Aug 2024

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Abstract

Benign prostatic hyperplasia (BPH) is a urogenital disorder that is common in aging men. Ixeris polycephala (IP) is used in traditional medicine and contains pharmacologically active compounds. However, the effect for BPH progression has not been elucidated. We herein examined the protective potential of IP extract on a testosterone-induced model of BPH in rats. To generate the BPH model, daily subcutaneous administration of testosterone was applied for 4 weeks. During this period, the rats were also administered a daily oral gavage of IP (150 mg/kg), finasteride (positive control), or vehicle. Testosterone treatment was associated with a significantly higher prostate-to-body weight ratio, serum dihydrotestosterone (DHT) level, and prostatic gene expression of 5α-reductase compared to untreated controls. Notably, IP plus testosterone co-treatment was associated with decreased epithelial thickness, down-regulation of proliferating cell nuclear antigen (PCNA) and cyclin D1, and upregulation of pro-apoptotic signaling molecules. IP co-treatment also down-regulated pro-inflammatory cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and decreased inflammatory cell infiltration compared to the levels seen in the testosterone-induced BPH. IP appears to protect rats against the progression of testosterone-induced BPH by alleviating prostate cell growth and inflammatory responses, and thus may have potential for clinical use against BPH progression. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2024)

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20 pages, 1446 KiB

Open AccessArticle

Nanoemulsified Essential Oil of Melaleuca leucadendron Leaves for Topical Application: In Vitro Photoprotective, Antioxidant and Anti-Melanoma Activities

by Lucas Resende Dutra Sousa, Maria Luiza da Costa Santos, Larissa Silva Sampaio, Clarisse Gaëlle Faustino, Mérine Lauriane Loïce Guigueno, Kátia Michelle Freitas, Miriam Teresa Paz Lopes, Gabriela Cristina Ferreira Mota, Viviane Martins Rebello dos Santos, Janaína Brandão Seibert, Tatiane Roquete Amparo, Paula Melo de Abreu Vieira, Orlando David Henrique dos Santos and Gustavo Henrique Bianco de Souza

Pharmaceuticals 2024, 17(6), 721; https://doi.org/10.3390/ph17060721 - 2 Jun 2024

Cited by 1 | Viewed by 1579

Abstract

Melanoma, primarily caused by solar ultraviolet (UV) radiation, can be prevented by the use of sunscreens. However, the use of synthetic sunscreens raises environmental concerns. Natural compounds with antioxidant photoprotective properties and cytotoxic effects against cancer cells can be promising for the prevention and treatment of melanoma with less environmental effect. This study focuses on Melaleuca leucadendron essential oil (EO) for photoprotection and antitumor applications. EO was hydrodistilled from M. leucadendron leaves with a 0.59% yield. Gas chromatography–mass spectrometry detected monoterpenes and sesquiterpenes. Nanoemulsions were prepared with (NE-EO) and without EO (NE-B) using the phase inversion method, showing good stability, spherical or oval morphology, and a pseudoplastic profile. Photoprotective activity assessed spectrophotometrically showed that the NE-EO was more effective than NE-B and free EO. Antioxidant activity evaluated by DPPH and ABTS methods indicated that pure and nanoemulsified EO mainly inhibited the ABTS radical, showing IC₅₀ 40.72 and 5.30 µg/mL, respectively. Cytotoxicity tests on L-929 mouse fibroblasts, NGM human melanocyte, B16-F10 melanoma, and MeWo human melanoma revealed that EO and NE-EO were more cytotoxic to melanoma cells than to non-tumor cells. The stable NE-EO demonstrates potential for melanoma prevention and treatment. Further research is required to gain a better understanding of these activities. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2024)

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13 pages, 1774 KiB

Open AccessArticle

Eugenol Inhibits Neutrophils Myeloperoxidase In Vitro and Attenuates LPS-Induced Lung Inflammation in Mice

by Amina Chniguir, Mohamed Hedi Saguem, Pham My-Chan Dang, Jamel El-Benna and Rafik Bachoual

Pharmaceuticals 2024, 17(4), 504; https://doi.org/10.3390/ph17040504 - 15 Apr 2024

Cited by 1 | Viewed by 1369

Abstract

Eugenol (Eug) is a polyphenol extracted from the essential oil of Syzygium aromaticum (L.) Merr. and Perry (Myrtaceae). The health benefits of eugenol in human diseases were proved in several studies. This work aims to evaluate the effect of eugenol on lung inflammatory disorders. For this, using human neutrophils, the antioxidant activity of eugenol was investigated in vitro. Furthermore, a model of LPS-induced lung injury in mice was used to study the anti-inflammatory effect of eugenol in vivo. Results showed that eugenol inhibits luminol-amplified chemiluminescence of resting neutrophils and after stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLF) peptide or phorbol myristate acetate (PMA). This effect was dose dependent and was significant from a low concentration of 0.1 µg/mL. Furthermore, eugenol inhibited myeloperoxidase (MPO) activity without affecting its degranulation. Eugenol has no scavenging effect on hydrogen peroxide (H₂O₂) and superoxide anion (O₂⁻). Pretreatment of mice with eugenol prior to the administration of intra-tracheal LPS significantly reduced neutrophil accumulation in the bronchoalveolar lavage fluid (BALF) and decreased total proteins concentration. Moreover, eugenol clearly inhibited the activity of matrix metalloproteinases MMP-2 (21%) and MMP-9 (28%), stimulated by LPS administration. These results suggest that the anti-inflammatory effect of eugenol against the LPS-induced lung inflammation could be exerted via inhibiting myeloperoxidase and metalloproteinases activity. Thus, eugenol could be a promising molecule for the treatment of lung inflammatory diseases. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2024)

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14 pages, 3526 KiB

Open AccessArticle

Comparative Antioxidant Potentials and Quantitative Phenolic Compounds Profiles among the Flowers and Leaves from Various Chrysanthemum morifolium Cultivars

by Tham Thi Mong Doan, Gia Han Tran, Toan Khac Nguyen, Ki Sung Kang, Jin Hee Lim and Sanghyun Lee

Pharmaceuticals 2024, 17(3), 340; https://doi.org/10.3390/ph17030340 - 6 Mar 2024

Cited by 2 | Viewed by 1326

Abstract

Chrysanthemum morifolium is a valuable plant that contains a wide range of phytochemical compounds and exhibits various biological activities. Ethanol extracts from both the leaves and flowers of 17 different cultivars of C. morifolium were tested for antioxidant activities using the 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) assays and were quantitatively analyzed for 12 phenolic compounds using high-performance liquid chromatography with diode-array detection. We found that the ‘Ford’ and ‘Raina’ cultivars demonstrated strong antioxidant abilities and high phenolic compound contents compared to other cultivars, while the flowers of ‘Cielo’ and the leaves of ‘White Cap’ exhibited low antioxidant capacity in both assays. The ‘Cielo’ cultivar also displayed the lowest compound contents. Additionally, in most samples, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid stood out as high-content compounds in the extracts. This study provides foundational knowledge that can be used for selecting appropriate C. morifolium cultivars for further research. Moreover, the ‘Ford’ and ‘Raina’ cultivars, containing high amounts of bioactive compounds and showing superior antioxidant ability, could be applied to produce health-beneficial products. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2024)

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13 pages, 2472 KiB

Open AccessArticle

Profiling the Phytochemicals of Orostachys margaritifolia: Biological Activities, LC-ESI/MS, and HPLC Analyses

by Nari Yoon, Hyeonjun Yu, Gia Han Tran, Chung Ho Ko, Hoon Kim, Mi Jeong Yoon and Sanghyun Lee

Pharmaceuticals 2024, 17(3), 290; https://doi.org/10.3390/ph17030290 - 23 Feb 2024

Cited by 1 | Viewed by 1251

Abstract

Orostachys margaritifolia Y. N. Lee (OMY) is an endemic Korean plant in the family Crassulaceae that is known to contain a variety of bioactive compounds. To assess the physiological activities of an OMY ethanol extract, ABTS⁺ and DPPH radical scavenging assays and a nitric oxide (NO) inhibition assay were conducted. The phytochemical makeup of the extract was profiled via liquid chromatography-mass spectrometry (LC-ESI/MS) and high-performance liquid chromatography with a photodiode array detector (HPLC/PDA). The OMY extract was found to have weaker ABTS⁺ and DPPH radical scavenging activities than the control group (green tea). In the NO inhibition assay, the OMY extract induced a significant increase in macrophage cell viability but showed a lower NO inhibitory activity than l-NAME, producing an IC₅₀ value of 202.6 μg/mL. The LC-ESI/MS and HPLC/PDA analyses identified isoquercitrin and astragalin in the OMY extract, quantifying their contents at 3.74 mg/g and 3.19 mg/g, respectively. The study revealed possibilities for the utilization of OMY as a future source of drugs for alleviating inflammation and diseases related to reactive oxygen species. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2024)

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Review

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35 pages, 4039 KiB

Open AccessReview

Jatropha Diterpenes: An Updated Review Concerning Their Structural Diversity, Therapeutic Performance, and Future Pharmaceutical Applications

by Thalisson A. de Souza, Luiz H. A. Pereira, Alan F. Alves, Douglas Dourado, Jociano da S. Lins, Marcus T. Scotti, Luciana Scotti, Lucas S. Abreu, Josean F. Tavares and Marcelo S. Silva

Pharmaceuticals 2024, 17(10), 1399; https://doi.org/10.3390/ph17101399 - 19 Oct 2024

Viewed by 1441

Abstract

The Euphorbiaceae family is a rich source of bioactive terpenoids. Among its genera, Jatropha is a conspicuous producer of diterpenes and includes approximately 175 species, many of which have medicinal uses. To date, 140 diterpenes from Jatropha (JTDs) have been reported. Given their structural diversity and notable biological activities, this work aims to highlight the pharmaceutical potential of JTDs. To achieve this goal, an extensive literature review was conducted, encompassing studies on structural elucidation through NMR and pharmacological assays, both in vitro and in vivo. Based on 132 selected papers, a thorough discussion is presented on the biosynthesis, extraction, isolation, and structural characterization of JTDs, including a compilation of their ¹³C NMR chemical shifts. The review also covers their synthetic production and biological effects. Additionally, an in silico analysis predicting the drug-likeness of 141 JTDs was carried out. Notably, the occurrence of macrocyclic diterpenes has doubled in the past decade, and the summary of their NMR data provides a useful resource for future research. Furthermore, 21 distinct pharmacological activities were identified, with potent cytotoxic effects targeting new molecular pathways being particularly significant. Recent advances highlight the contributions of modern approaches in organic synthesis and the pharmacological evaluation of natural products. The drug-likeness analysis identified JTD classes and compounds with favorable physicochemical and ADMET features for pharmaceutical development. In light of these findings, the use of nanotechnology is proposed as a future direction for continued research on JTDs, a fascinating class of natural compounds. This work opens up new avenues for the study of Euphorbiaceae species, particularly the Jatropha genus and its bioactive compounds. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2024)

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