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Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022
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Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022

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

Deadline for manuscript submissions: closed (15 August 2023) | Viewed by 53842

Special Issue Editors

Dr. Dejan Stojković

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Guest Editor
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

E-Mail Website
Guest Editor
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 a hot topic field. Many in vitro studies describe the beneficial effects of plants for human health, highlighting promising pharmacological effects.

This thematic 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 includes plant mixtures, please do check the following:

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

The scope of the thematic issue will cover but is not limited to:

  • - 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

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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15 pages, 3939 KiB  
Article
Anti-Inflammatory Effect of Cinnamomum japonicum Siebold’s Leaf through the Inhibition of p38/JNK/AP-1 Signaling
by Ji Min Kim, In A Jung, Jae Min Kim, Moon-Hee Choi and Ji Hye Yang
Pharmaceuticals 2023, 16(10), 1402; https://doi.org/10.3390/ph16101402 - 03 Oct 2023
Cited by 1 | Viewed by 806
Abstract
Cinnamomum japonicum Siebold (CJ) branch bark, commonly known as Japanese cinnamon, has been used for various culinary and medicinal applications for many centuries. Although the efficacy of CJ branch bark’s anti-inflammatory and antioxidant activity for the treatment of various diseases has been confirmed, [...] Read more.
Cinnamomum japonicum Siebold (CJ) branch bark, commonly known as Japanese cinnamon, has been used for various culinary and medicinal applications for many centuries. Although the efficacy of CJ branch bark’s anti-inflammatory and antioxidant activity for the treatment of various diseases has been confirmed, the efficacy of CJ leaves (CJLs) has not been examined. We therefore investigated whether CJL3, an ethyl acetate extract of a 70% ethanol CJL extract, exerts anti-inflammatory effects on lipopolysaccharide (LPS)-activated Kupffer cells, specialized macrophages found in the liver. Liver inflammation can activate Kupffer cells, inducing the release of pro-inflammatory molecules that contribute to tissue damage. We found that CJL3 has high 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) radical-scavenging activity. Among the CJL extracts, CJL3 exhibited the greatest polyphenol content, with protocatechuic acid and 4-hydroxybenzoic acid being the most abundant. In addition, we verified that CJL3, which has strong antioxidant properties, ameliorates LPS-induced pro-inflammatory responses by inhibiting p38/JNK/AP-1 signaling. CJL3 therefore has potential for treating liver disease, including hepatitis. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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12 pages, 1424 KiB  
Article
The Adapted POM Analysis of Avenanthramides In Silico
by Tibor Maliar, Mária Maliarová, Andrea Purdešová, Timotej Jankech, Ivana Gerhardtová, Patrik Beňovič, Václav Dvořáček, Michal Jágr and Jana Viskupičová
Pharmaceuticals 2023, 16(5), 717; https://doi.org/10.3390/ph16050717 - 09 May 2023
Cited by 6 | Viewed by 1605
Abstract
POM analysis and related approaches are significant tools based on calculating various physico-chemical properties and predicting biological activity, ADME parameters, and toxicity of a molecule. These methods are used to evaluate a molecule’s potential to become a drug candidate. Avenanthramides (AVNs) are promising [...] Read more.
POM analysis and related approaches are significant tools based on calculating various physico-chemical properties and predicting biological activity, ADME parameters, and toxicity of a molecule. These methods are used to evaluate a molecule’s potential to become a drug candidate. Avenanthramides (AVNs) are promising secondary metabolites specific to Avena spp. (oat). They comprise the amides of anthranilic acid linked to various polyphenolic acids with or without post-condensation molecule transformation. These natural compounds have been reported to exert numerous biological effects, including antioxidant, anti-inflammatory, hepatoprotective, antiatherogenic, and antiproliferative properties. To date, almost 50 various AVNs have been identified. We performed a modified POM analysis of 42 AVNs using MOLINSPIRATION, SWISSADME, and OSIRIS software. The evaluation of primary in silico parameters revealed significant differences among individual AVNs, highlighting the most promising candidates. These preliminary results may help coordinate and initiate other research projects focused on particular AVNs, especially those with predicted bioactivity, low toxicity, optimal ADME parameters, and promising perspectives. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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25 pages, 5536 KiB  
Article
Biomarker Quantification, Spectroscopic, and Molecular Docking Studies of the Active Compounds Isolated from the Edible Plant Sisymbrium irio L.
by Shaza M. Al-Massarani, Latifah S. Aldurayhim, Ibtisam A. Alotaibi, Mostafa W. M. Abdelmageed, Md Tabish Rehman, Omer A. Basudan, Maged S. Abdel-Kader, Mohamed F. Alajmi, Fatma M. Abdel Bar, Perwez Alam, Maram M. Al Tamimi and Ali A. El Gamal
Pharmaceuticals 2023, 16(4), 498; https://doi.org/10.3390/ph16040498 - 27 Mar 2023
Viewed by 1490
Abstract
Phytochemical investigation of the ethanolic extract of the aerial parts of Sisymbrium irio L. led to the isolation of four unsaturated fatty acids (1–4), including a new one (4), and four indole alkaloids (5–8 [...] Read more.
Phytochemical investigation of the ethanolic extract of the aerial parts of Sisymbrium irio L. led to the isolation of four unsaturated fatty acids (1–4), including a new one (4), and four indole alkaloids (5–8). The structures of the isolated compounds were characterized with the help of spectroscopic techniques such as 1D, 2D NMR, and mass spectroscopy, and by correlation with the known compounds. In terms of their notable structural diversity, a molecular docking approach with the AutoDock 4.2 program was used to analyze the interactions of the identified fatty acids with PPAR-γ and the indole alkaloids with 5-HT1A and 5-HT2A, subtypes of serotonin receptors, respectively. Compared to the antidiabetic drug rivoglitazone, compound 3 acted as a potential PPAR-γ agonist with a binding energy of −7.4 kcal mol−1. Moreover, compound 8 displayed the strongest affinity, with binding energies of −6.9 kcal/mol to 5HT1A and −8.1 kcal/mol to 5HT2A, using serotonin and the antipsychotic drug risperidone as positive controls, respectively. The results of docked conformations represent an interesting target for developing novel antidiabetic and antipsychotic drugs and warrant further evaluation of these ligands in vitro and in vivo. On the other hand, an HPTLC method was developed to quantify α-linolenic acid in the hexane fraction of the ethanol extract of S. irio. The regression equation/correlation coefficient (r2) for linolenic acid was Y = 6.49X + 2310.8/0.9971 in the linearity range of 100–1200 ng/band. The content of α-linolenic acid in S. irio aerial parts was found to be 28.67 μg/mg of dried extract. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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18 pages, 8448 KiB  
Article
The In Vitro Anti-Parasitic Activities of Emodin toward Toxoplasma gondii
by Oluyomi Stephen Adeyemi, Kosei Ishii and Kentaro Kato
Pharmaceuticals 2023, 16(3), 447; https://doi.org/10.3390/ph16030447 - 16 Mar 2023
Viewed by 1568
Abstract
Currently, toxoplasmosis affects nearly one-third of the world’s population, but the available treatments have several limitations. This factor underscores the search for better therapy for toxoplasmosis. Therefore, in the current investigation, we investigated the potential of emodin as a new anti-Toxoplasma gondii [...] Read more.
Currently, toxoplasmosis affects nearly one-third of the world’s population, but the available treatments have several limitations. This factor underscores the search for better therapy for toxoplasmosis. Therefore, in the current investigation, we investigated the potential of emodin as a new anti-Toxoplasma gondii while exploring its anti-parasitic mechanism of action. We explored the mechanisms of action of emodin in the presence and absence of an in vitro model of experimental toxoplasmosis. Emodin showed strong anti-T. gondii action with an EC50 value of 0.03 µg/mL; at this same effective anti-parasite concentration, emodin showed no appreciable host cytotoxicity. Likewise, emodin showed a promising anti-T. gondii specificity with a selectivity index (SI) of 276. Pyrimethamine, a standard drug for toxoplasmosis, had an SI of 2.3. The results collectively imply that parasite damage was selective rather than as a result of a broad cytotoxic effect. Furthermore, our data confirm that emodin-induced parasite growth suppression stems from parasite targets and not host targets, and indicate that the anti-parasite action of emodin precludes oxidative stress and ROS production. Emodin likely mediates parasite growth suppression through means other than oxidative stress, ROS production, or mitochondrial toxicity. Collectively, our findings support the potential of emodin as a promising and novel anti-parasitic agent that warrants further investigation. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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17 pages, 1387 KiB  
Article
Solvent System-Guided Extraction of Centaurium spicatum (L.) Fritch Provides Optimized Conditions for the Biological and Chemical Characteristics of the Herbal Extracts
by Jelena Božunović, Marija Ivanov, Jovana Petrović, Uroš Gašić, Đura Nakarada, Milica Milutinović, Neda Aničić, Zlatko Giba, Danijela Mišić and Dejan Stojković
Pharmaceuticals 2023, 16(2), 245; https://doi.org/10.3390/ph16020245 - 06 Feb 2023
Cited by 1 | Viewed by 1377
Abstract
Spiked centaury (Centaurium spicatum) is a well-known medicinal plant from the Mediterranean region with various bioactivities, but there are no studies addressing the use of different solvent systems to improve its pharmacological potential. Nine extraction procedures were adapted to study the [...] Read more.
Spiked centaury (Centaurium spicatum) is a well-known medicinal plant from the Mediterranean region with various bioactivities, but there are no studies addressing the use of different solvent systems to improve its pharmacological potential. Nine extraction procedures were adapted to study the effects of solvent composition on the content of bioactive compounds in C. spicatum extracts and on corresponding bioactivities. Targeted metabolomics was performed to obtain information on the chemical composition of extracts. Ethanol-water-based extraction procedures were the most efficient in isolating polyphenols, while less polar butanol extract contained the highest amount of iridoids. Antioxidant potential analysis revealed stronger activity in extracts with higher polyphenol content. Bacillus cereus and Staphylococus aureus were designated as the most sensitive bacterial strains to the activity of extracts, while among the micromycetes tested, Penicillium funiculosum was the most susceptible strain. Butanol extract showed antivirulence potential on Candida albicans morphological transition from yeast to hyphal form, and selected extracts were effective against biofilm formation in two Candida species. All the extracts tested in this study showed no cytotoxic activity to immortalize human skin keratinocyte cell line (HaCaT), whereas extracts obtained by ethanol-water extraction stand out for their potent wound healing effects. Moreover, the influence of the extraction solvent system on various bioactivities of C. spicatum is reported herein for the first time. Overall, the results presented in this study promote the use of C. spicatum as a source of natural products with potential antioxidant, wound healing, and antimicrobial applications that are potentially safe for human use. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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17 pages, 2008 KiB  
Article
Exploration of the Antioxidant and Anti-inflammatory Potential of Cassia sieberiana DC and Piliostigma thonningii (Schumach.) Milne-Redh, Traditionally Used in the Treatment of Hepatitis in the Hauts-Bassins Region of Burkina Faso
by Eliasse Zongo, Anna Busuioc, Roland Nâg-Tiero Meda, Andreea Veronica Botezatu, Maria Daniela Mihaila, Ana-Maria Mocanu, Sorin Marius Avramescu, Benjamin Kouliga Koama, Sami Eric Kam, Hadidiatou Belem, Franck Le Sage Somda, Clarisse Ouedraogo, Georges Anicet Ouedraogo and Rodica Mihaela Dinica
Pharmaceuticals 2023, 16(1), 133; https://doi.org/10.3390/ph16010133 - 16 Jan 2023
Cited by 2 | Viewed by 2850
Abstract
Inflammation is the supreme biological response to illness. In the Hauts-Bassins region, in traditional medicine, all parts of Cassia sieberiana and Piliostigma thonningii are used to treat hepatitis and inflammation. The aim of this study was to evaluate the in vitro antioxidant and [...] Read more.
Inflammation is the supreme biological response to illness. In the Hauts-Bassins region, in traditional medicine, all parts of Cassia sieberiana and Piliostigma thonningii are used to treat hepatitis and inflammation. The aim of this study was to evaluate the in vitro antioxidant and anti-inflammatory activities of their aqueous extracts. High performance liquid chromatography with photodiode array (HPLC-DAD) and ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-MS/MS) analyses highlighted the presence of polyphenols and flavonoids. Antioxidant and anti-inflammatory activities were measured by various methods such as DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), TAC (total antioxidant capacity), anti-protease, anti-lipoxygenase, and membrane stabilization. The best antioxidant activity was observed in the bark (DPPH: IC50 = 13.45 ± 0.10 µg/mL) and roots (TAC = 29.68 ± 1.48 mg AAE/g DW) of Piliostigma thonningii and in the roots (ABTS: IC50 = 1.83 ± 0.34 µg/mL) of Cassia sieberiana. The best anti-inflammatory activity was observed in the bark (anti-lipoxygenase: IC50 = 13.04 ± 1.99 µg/mL) and leaves (anti-proteases: IC50 = 75.74 ± 1.07 µg/mL, membrane stabilization: IC50 = 48.32 ± 6.39 µg/mL) of Cassia sieberiana. Total polyphenols (ABTS: r = −0.679, TAC: r = 0.960) and condensed tannins (ABTS: r = −0.702, TAC: r = 0.701) were strongly correlated with antioxidant activity. Total flavonoids (anti-proteases: r = −0.729), condensed tannins (anti-proteases: r = 0.698), and vitamin C (anti-proteases: r = −0.953) were strongly correlated with anti-inflammatory activity. Total polyphenols, flavonoids, condensed tannins, and vitamin C could contribute to the antioxidant and anti-inflammatory activities of the two studied plants. These results could validate the traditional use of these plants to treat various inflammatory diseases. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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11 pages, 2471 KiB  
Article
Role of Herbal Extracts of Catechu from Uncaria gambir in the Treatment of Chronic Diabetic Wounds
by Tsung-Jung Ho, Pei-Hsuan Tsai, Chia-Ho Hsieh, Jung-Hsing Lin, Yu-Wei Lin, Jia-Ru Wu and Hao-Ping Chen
Pharmaceuticals 2023, 16(1), 66; https://doi.org/10.3390/ph16010066 - 31 Dec 2022
Cited by 3 | Viewed by 1993
Abstract
Catechu is a dried decoction from twigs with the leaves of Uncaria gambir. Its antioxidant, anti-inflammatory, and antimicrobial activities have been previously reported because of its high catechin and epicatechin content (>21%). It is also one of the components used in traditional [...] Read more.
Catechu is a dried decoction from twigs with the leaves of Uncaria gambir. Its antioxidant, anti-inflammatory, and antimicrobial activities have been previously reported because of its high catechin and epicatechin content (>21%). It is also one of the components used in traditional Chinese herbal medicine, “Jinchuang Ointment,” which has excellent efficacy in treating chronic diabetic wounds. An in vivo zebrafish embryo platform and an in vitro cell-based tube formation assay were used to measure the angiogenic activity of catechu extracts. Interestingly, for the first time, catechu extracts stimulated angiogenic activity on both platforms. The expression of the IL-8 gene was induced in HMEC1 cells after treatment with catechu extracts for 1 h only. In contrast, the upregulation of FGFR2, FGFR3, NF-κB, STAT3, and vimentin persisted for 24 h. A summary of the possible mechanisms underlying the angiogenic activity of catechu extracts in HMEC1 cells is shown. Unexpectedly, catechu extracts inhibited the migration of HaCaT cells. These results can account for the intense blood flow flux in porcine excisional wound sites in our previous studies, which provides insights into the therapeutic activity of catechu extract in chronic diabetic wounds. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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20 pages, 1568 KiB  
Article
Chemical and Biological Investigations of Allium scorodoprasum L. Flower Extracts
by Nikoleta Đorđevski, Abdullahi Ibrahim Uba, Gokhan Zengin, Jelena Božunović, Uroš Gašić, Elizabeta Ristanović, Ana Ćirić, Biljana Nikolić and Dejan Stojković
Pharmaceuticals 2023, 16(1), 21; https://doi.org/10.3390/ph16010021 - 23 Dec 2022
Cited by 4 | Viewed by 1899
Abstract
This study was designed to investigate the impact of different extraction solvent systems on the chemical composition and biological activities of Allium scorodoprasum L. (Amaryllidaceae)—the medicinal plant that was traditionally used as a remedy in the medieval period in the Balkans. Targeted chemical [...] Read more.
This study was designed to investigate the impact of different extraction solvent systems on the chemical composition and biological activities of Allium scorodoprasum L. (Amaryllidaceae)—the medicinal plant that was traditionally used as a remedy in the medieval period in the Balkans. Targeted chemical analysis of nine different extracts was performed by UHPLC(−)HESI–QqQ-MS/MS. Antimicrobial and antibiofilm activities of the extracts were investigated on sixteen clinical isolates of bacteria, yeasts and dermatomycetes, all isolated from infected human skin and corneal formations. Cytotoxicity and wound-healing properties were tested on human immortalized keratinocytes (HaCaT cell line). Antioxidant activity was assessed by six different assays, while beneficial potential against certain neurodegenerative diseases and type 2 diabetes was determined in selected enzyme inhibition assays coupled with molecular modeling. The results showed that the obtained extracts were rich in phenolic compounds, especially flavonoid glycosides such as rutin and kaempferol 3-O-glucoside. All of the extracts showed antimicrobial, wound-healing, antioxidant and anti-enzymatic properties. This study is the first of its kind, linking the medieval medicinal use of wild-growing flowers of A. scorodoprasum with contemporary in vitro scientific approaches. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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26 pages, 2905 KiB  
Article
Chemical Profile and Skin-Beneficial Activities of the Petal Extracts of Paeonia tenuifolia L. from Serbia
by Natalija Čutović, Tatjana Marković, Marina Kostić, Uroš Gašić, Željana Prijić, Xiuxia Ren, Milan Lukić and Branko Bugarski
Pharmaceuticals 2022, 15(12), 1537; https://doi.org/10.3390/ph15121537 - 11 Dec 2022
Cited by 7 | Viewed by 2258
Abstract
Without being aware of its chemical makeup, many ancient societies have used Steppe peony in their traditional medicine. Given that modern phytopreparation intended for use on human skin requires, above all, knowledge of its chemical composition, the goal of this study was to [...] Read more.
Without being aware of its chemical makeup, many ancient societies have used Steppe peony in their traditional medicine. Given that modern phytopreparation intended for use on human skin requires, above all, knowledge of its chemical composition, the goal of this study was to make a screening of the composition of aqueous and methanolic extracts of the petals of P. tenuifolia L. and to examine them for various skin-beneficial properties. The extracts were prepared by maceration, ultrasound-assisted, and microwave-assisted extraction procedures. The chemical profiling was conducted by the use of UHPLC-LTQ-OrbiTrap MS and UHPLC/MS, and spectrophotometric methods for the determination of total polyphenol and total flavonoid contents. The biological activities entailed antioxidant ABTS, DPPH, CUPRAC (Cupric Ion Reducing Antioxidant Capacity), and FRAP (Ferric Reducing Antioxidant Power) assays, antimicrobial (antibacterial and antifungal) and antibiofilm activities, cytotoxicity, wound healing potential, as well as the adhesion and invasion of Staphylococcus lugdunensis. The results showed that the petals are rich in phenolic acids and flavonoids, which are commonly associated with numerous biological activities. The aqueous extracts were more efficient in the majority of the bioactivity assays then the methanolic ones, whereas the optimal extraction method varied between the assays. This study is the first step towards the safe use of the aqueous extracts of P. tenuifolia petals for therapeutic skin treatments. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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31 pages, 6264 KiB  
Article
Agathis robusta Bark Extract Protects from Renal Ischemia-Reperfusion Injury: Phytochemical, In Silico and In Vivo Studies
by Maged E. Mohamed, Nora Tawfeek, Samar S. Elbaramawi, Mahmoud H. Elbatreek and Eman Fikry
Pharmaceuticals 2022, 15(10), 1270; https://doi.org/10.3390/ph15101270 - 14 Oct 2022
Cited by 8 | Viewed by 2297
Abstract
Background: Acute kidney injury (AKI) induced by renal ischemia-reperfusion injury (RIRI) is associated with a high incidence of mortality. Existing therapies are mainly supportive, with no available nephroprotective agent. The purpose of this study is to examine the potential protective effect of Agathis [...] Read more.
Background: Acute kidney injury (AKI) induced by renal ischemia-reperfusion injury (RIRI) is associated with a high incidence of mortality. Existing therapies are mainly supportive, with no available nephroprotective agent. The purpose of this study is to examine the potential protective effect of Agathis robusta Bark Extract (ARBE) in RIRI. Methods: The chemical composition of ARBE was examined by LC-ESI-MS/MS. Network pharmacology was utilized to identify the RIRI molecular targets that could be aimed at by the identified major components of ARBE. Experimentally validated protein–protein interactions (PPIs) and compound-target networks were constructed using the STRING database and Cytoscape software. Molecular docking studies were employed to assess the interaction of the most relevant ARBE compounds with the hub RIRI-related targets. Furthermore, ARBE was tested in a rat model of RIRI. Results: The phytochemical analysis identified 95 components in ARBE, 37 of which were majors. Network analysis identified 312 molecular targets of RIRI that were associated with ARBE major compounds. Of these 312, the top targets in the experimentally validated PPI network were HSP90, EGFR, and P53. The most relevant compounds based on their peak area and network degree value included narcissoside, isorhamnetin-3-O-glucoside, and syringetin-3-O-glucoside, among others. Docking studies of the most relevant compounds revealed significant interactions with the top RIRI-related targets. In the in vivo RIRI experiments, pretreatment of ARBE improved kidney function and structural changes. ARBE reduced the renal expression of p-NfkB and cleaved caspase-3 by downregulating HSP90 and P53 in rats exposed to RIRI. Conclusion: Taken together, this study revealed the chemical composition of ARBE, depicted the interrelationship of the bioactive ingredients of ARBE with the RIRI-related molecular targets, and validated a nephroprotective effect of ARBE in RIRI. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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29 pages, 3940 KiB  
Article
The Role of Myrrh Metabolites in Cancer, Inflammation, and Wound Healing: Prospects for a Multi-Targeted Drug Therapy
by Rasha Saad Suliman, Sahar Saleh Alghamdi, Rizwan Ali, Dimah Aljatli, Norah Abdulaziz Aljammaz, Sarah Huwaizi, Rania Suliman, Khawla Mohammed Kahtani, Ghadeer M. Albadrani, Tlili Barhoumi, Abdulelah Altolayyan and Ishrat Rahman
Pharmaceuticals 2022, 15(8), 944; https://doi.org/10.3390/ph15080944 - 29 Jul 2022
Cited by 12 | Viewed by 5882
Abstract
Background: Myrrh extract is a well-known medicinal plant with significant therapeutic benefits attributed to the activity of its diverse metabolites. It has promising activity against cancer and inflammatory diseases, and could serve as a potential therapeutic alternative since most therapeutic agents have severe [...] Read more.
Background: Myrrh extract is a well-known medicinal plant with significant therapeutic benefits attributed to the activity of its diverse metabolites. It has promising activity against cancer and inflammatory diseases, and could serve as a potential therapeutic alternative since most therapeutic agents have severe side effects that impair quality of life. Method: The current study identified the active metabolites from the myrrh resin methanolic extract. Then, the extracts were tested for in vitro anti-inflammatory and anti-cancer activity using cancer cell lines and Tamm-Horsfall Protein 1 (Thp-1)-like macrophage cell lines. Furthermore, using an in vivo rat model, the extracts’ anti-inflammatory and wound-healing activity was investigated. In addition, in silico predictions of the myrrh constituents highlighted the pharmacokinetic properties, molecular targets, and safety profile, including cytochrome P 450 (CYP) inhibition and organ toxicity. Results: Nine secondary metabolites were identified, and computational predictions suggested a good absorption profile, anticancer, anti-inflammatory, and wound-healing effects. The myrrh extract had moderate cytotoxic activity against both HL60 and K562 leukemia cell lines and the KAIMRC1 breast cancer cell line. Myrrh caused a dose-dependent effect on macrophages to increase the reactive oxygen species (ROS) levels, promote their polarization to classically activated macrophages (M1) and alternatively activated macrophages (M2) phenotypes, and consequently induce apoptosis, highlighting its ability to modulate macrophage function, which could potentially aid in several desired therapeutic processes, including the resolution of inflammation, and autophagy which is an important aspect to consider in cancer treatment. The topical application of myrrh improved wound healing, with no delayed inflammatory response, and promoted complete re-epithelization of the skin, similar to the positive control. In conclusion, we provide evidence for the methanolic extract of myrrh having cytotoxic activity against cancer cells and anti-inflammatory wound-healing properties, which may be attributed to its role in modulating macrophage function. Furthermore, we suggest the active constituents responsible for these properties, which warrants further studies focusing on the precise roles of the active metabolites. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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15 pages, 3012 KiB  
Article
Short-Term Administration of Lemon Balm Extract Ameliorates Myocardial Ischemia/Reperfusion Injury: Focus on Oxidative Stress
by Nevena Draginic, Isidora Milosavljevic, Marijana Andjic, Jovana Jeremic, Marina Nikolic, Jasmina Sretenovic, Aleksandar Kocovic, Ivan Srejovic, Vladimir Zivkovic, Sergey Bolevich, Stefani Bolevich, Svetlana Curcic and Vladimir Jakovljevic
Pharmaceuticals 2022, 15(7), 840; https://doi.org/10.3390/ph15070840 - 08 Jul 2022
Cited by 4 | Viewed by 1637
Abstract
We aimed to investigate the cardioprotective effects of ethanolic Melissa officinalis L. extract (ME) in the rat model of myocardial ischemia/reperfusion (I/R) injury. Thirty-two Wistar rats were randomly divided into a CTRL non-treated control group with myocardial I/R injury and three experimental groups [...] Read more.
We aimed to investigate the cardioprotective effects of ethanolic Melissa officinalis L. extract (ME) in the rat model of myocardial ischemia/reperfusion (I/R) injury. Thirty-two Wistar rats were randomly divided into a CTRL non-treated control group with myocardial I/R injury and three experimental groups of rats treated with 50, 100, or 200 mg/kg of ME for 7 days per os. Afterward, hearts were isolated, and cardiodynamic function was assessed via the Langendorff model of global 20 min ischemia and 30 min reperfusion. Oxidative stress parameters were determined spectrophotometrically from the samples of coronary venous effluent (O2−, H2O2, TBARS, and NO2−,) and heart tissue homogenate (TBARS, NO2−, SOD, and CAT). H/E and Picrosirius red staining were used to examine cardiac architecture and cardiac collagen content. ME improved cardiodynamic parameters and achieved to preserve cardiac architecture after I/R injury and to decrease fibrosis, especially in the ME200 group compared to CTRL. ME200 and ME100 markedly decreased prooxidants TBARS, O2−, and H2O2 while increasing NO2−. Hereby, we confirmed the ME`s ability to save the heart from I/R induced damage, even after short-term preconditioning in terms of preserving cardiodynamic alterations, cardiac architecture, fibrosis, and suppressing oxidative stress, especially in dose of 200 mg/kg. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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Review

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40 pages, 5067 KiB  
Review
Tailoring Potential Natural Compounds for the Treatment of Luminal Breast Cancer
by Fernanda Cardoso da Silva, Douglas Cardoso Brandão, Everton Allan Ferreira, Raoni Pais Siqueira, Helen Soares Valença Ferreira, Ademar Alves Da Silva Filho and Thaise Gonçalves Araújo
Pharmaceuticals 2023, 16(10), 1466; https://doi.org/10.3390/ph16101466 - 16 Oct 2023
Cited by 1 | Viewed by 1681
Abstract
Breast cancer (BC) is the most diagnosed cancer worldwide, mainly affecting the epithelial cells from the mammary glands. When it expresses the estrogen receptor (ER), the tumor is called luminal BC, which is eligible for endocrine therapy with hormone signaling blockade. Hormone therapy [...] Read more.
Breast cancer (BC) is the most diagnosed cancer worldwide, mainly affecting the epithelial cells from the mammary glands. When it expresses the estrogen receptor (ER), the tumor is called luminal BC, which is eligible for endocrine therapy with hormone signaling blockade. Hormone therapy is essential for the survival of patients, but therapeutic resistance has been shown to be worrying, significantly compromising the prognosis. In this context, the need to explore new compounds emerges, especially compounds of plant origin, since they are biologically active and particularly promising. Natural products are being continuously screened for treating cancer due to their chemical diversity, reduced toxicity, lower side effects, and low price. This review summarizes natural compounds for the treatment of luminal BC, emphasizing the activities of these compounds in ER-positive cells. Moreover, their potential as an alternative to endocrine resistance is explored, opening new opportunities for the design of optimized therapies. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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32 pages, 3801 KiB  
Review
Natural Compounds of Fungal Origin with Antimicrobial Activity—Potential Cosmetics Applications
by Katarzyna Sułkowska-Ziaja, Monika Trepa, Aldona Olechowska-Jarząb, Paweł Nowak, Marek Ziaja, Katarzyna Kała and Bożena Muszyńska
Pharmaceuticals 2023, 16(9), 1200; https://doi.org/10.3390/ph16091200 - 23 Aug 2023
Cited by 2 | Viewed by 3879
Abstract
The phenomenon of drug resistance in micro-organisms necessitates the search for new compounds capable of combating them. Fungi emerge as a promising source of such compounds as they produce a wide range of secondary metabolites with bacteriostatic or fungistatic activity. These compounds can [...] Read more.
The phenomenon of drug resistance in micro-organisms necessitates the search for new compounds capable of combating them. Fungi emerge as a promising source of such compounds as they produce a wide range of secondary metabolites with bacteriostatic or fungistatic activity. These compounds can serve as alternatives for commonly used antibiotics. Furthermore, fungi also accumulate compounds with antiviral activity. This review focuses on filamentous fungi and macrofungi as sources of antimicrobial compounds. The article describes both individual isolated compounds and extracts that exhibit antibacterial, antifungal, and antiviral activity. These compounds are produced by the fruiting bodies and mycelium, as well as the biomass of mycelial cultures. Additionally, this review characterizes the chemical compounds extracted from mushrooms used in the realm of cosmetology; specifically, their antimicrobial activity. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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14 pages, 1785 KiB  
Review
Medicinal Characteristics of Withania somnifera L. in Colorectal Cancer Management
by John M. Macharia, Zsolt Káposztás and Raposa L. Bence
Pharmaceuticals 2023, 16(7), 915; https://doi.org/10.3390/ph16070915 - 22 Jun 2023
Cited by 5 | Viewed by 2587
Abstract
Research into tumorigenic pathways can aid in the development of more efficient cancer therapies and provide insight into the physiological regulatory mechanisms employed by rapidly proliferating cancer cells. Due to the severe side effects of cancer chemotherapeutic medications, plant chemicals and their analogues [...] Read more.
Research into tumorigenic pathways can aid in the development of more efficient cancer therapies and provide insight into the physiological regulatory mechanisms employed by rapidly proliferating cancer cells. Due to the severe side effects of cancer chemotherapeutic medications, plant chemicals and their analogues are now explored more frequently for the treatment and prevention of colorectal cancer (CRC), opening the stage for new phytotherapeutic strategies that are considered effective and safe substitutes. Our study aimed to evaluate the medicinal properties of Withania somnifera L. and its safety applications in CRC management. Important databases were rigorously searched for relevant literature, and only 82 full-text publications matched the inclusion requirements from a massive collection of 10,002 titles and abstracts. W. somnifera L. contains a high concentration of active plant-based compounds. The pharmacological activity of the plant from our study has been demonstrated to exert antiproliferation, upregulation of apoptosis, decrease in oxidative stress, downregulation of cyclooxygenase-2 (COX-2), induction of targeted cytotoxic effects on cancerous cells, and exertion of both antiangiogenesis and antimigratory effects. We advise further research before recommending W. somnifera L. for clinical use to identify the optimal concentrations required to elicit beneficial effects in CRC management in humans, singly or in combination. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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25 pages, 1765 KiB  
Review
Therapeutic Potential of Hibiscus sabdariffa Linn. in Attenuating Cardiovascular Risk Factors
by Syaifuzah Sapian, Asma Ali Ibrahim Mze, Fatin Farhana Jubaidi, Nor Anizah Mohd Nor, Izatus Shima Taib, Zariyantey Abd Hamid, Satirah Zainalabidin, Nur Najmi Mohamad Anuar, Haliza Katas, Jalifah Latip, Juriyati Jalil, Nur Faizah Abu Bakar and Siti Balkis Budin
Pharmaceuticals 2023, 16(6), 807; https://doi.org/10.3390/ph16060807 - 29 May 2023
Cited by 4 | Viewed by 3865
Abstract
Cardiovascular diseases (CVDs) represent a broad spectrum of diseases afflicting the heart and blood vessels and remain a major cause of death and disability worldwide. CVD progression is strongly associated with risk factors, including hypertension, hyperglycemia, dyslipidemia, oxidative stress, inflammation, fibrosis, and apoptosis. [...] Read more.
Cardiovascular diseases (CVDs) represent a broad spectrum of diseases afflicting the heart and blood vessels and remain a major cause of death and disability worldwide. CVD progression is strongly associated with risk factors, including hypertension, hyperglycemia, dyslipidemia, oxidative stress, inflammation, fibrosis, and apoptosis. These risk factors lead to oxidative damage that results in various cardiovascular complications including endothelial dysfunctions, alterations in vascular integrity, the formation of atherosclerosis, as well as incorrigible cardiac remodeling. The use of conventional pharmacological therapy is one of the current preventive measures to control the development of CVDs. However, as undesirable side effects from drug use have become a recent issue, alternative treatment from natural products is being sought in medicinal plants and is gaining interest. Roselle (Hibiscus sabdariffa Linn.) has been reported to contain various bioactive compounds that exert anti-hyperlipidemia, anti-hyperglycemia, anti-hypertension, antioxidative, anti-inflammation, and anti-fibrosis effects. These properties of roselle, especially from its calyx, have relevance to its therapeutic and cardiovascular protection effects in humans. This review summarizes the findings of recent preclinical and clinical studies on roselle as a prophylactic and therapeutic agent in attenuating cardiovascular risk factors and associated mechanisms. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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15 pages, 1324 KiB  
Review
Synthesis and Biological Activities of Dehydrodiisoeugenol: A Review
by Beatriz Godínez-Chaparro, Salud Pérez-Gutiérrez, Julia Pérez-Ramos, Ivo Heyerdahl-Viau and Liliana Hernández-Vázquez
Pharmaceuticals 2022, 15(11), 1351; https://doi.org/10.3390/ph15111351 - 31 Oct 2022
Cited by 2 | Viewed by 1773
Abstract
Dehydrodiisoeugenol (DHIE) is a neolignan found in more than 17 plant species, including herbs, fruit, and root. DHIE was, for the first time, isolated from Myristica fragrans bark in 1973. Since then, many methodologies have been used for the obtention of DHIE, including [...] Read more.
Dehydrodiisoeugenol (DHIE) is a neolignan found in more than 17 plant species, including herbs, fruit, and root. DHIE was, for the first time, isolated from Myristica fragrans bark in 1973. Since then, many methodologies have been used for the obtention of DHIE, including classical chemistry synthesis using metal catalysts and biocatalytic synthesis; employing horseradish peroxidase; peroxidase from Cocos nucifera; laccase; culture cells of plants; and microorganisms. Increasing evidence has indicated that DHIE has a wide range of biological activities: anti-inflammatory, anti-oxidant, anti-cancerogenic, and anti-microbial properties. However, evidence in vivo and in human beings is still lacking to support the usefulness potential of DHIE as a therapeutic agent. This study’s review was created by searching for relevant DHIE material on websites such as Google Scholar, PubMed, SciFinder, Scholar, Science Direct, and others. This reviews the current state of knowledge regarding the different synthetical routes and biological applications of DHIE. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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17 pages, 2032 KiB  
Review
Xylan Prebiotics and the Gut Microbiome Promote Health and Wellbeing: Potential Novel Roles for Pentosan Polysulfate
by Margaret M. Smith and James Melrose
Pharmaceuticals 2022, 15(9), 1151; https://doi.org/10.3390/ph15091151 - 16 Sep 2022
Cited by 2 | Viewed by 3079
Abstract
This narrative review highlights the complexities of the gut microbiome and health-promoting properties of prebiotic xylans metabolized by the gut microbiome. In animal husbandry, prebiotic xylans aid in the maintenance of a healthy gut microbiome. This prevents the colonization of the gut by [...] Read more.
This narrative review highlights the complexities of the gut microbiome and health-promoting properties of prebiotic xylans metabolized by the gut microbiome. In animal husbandry, prebiotic xylans aid in the maintenance of a healthy gut microbiome. This prevents the colonization of the gut by pathogenic organisms obviating the need for dietary antibiotic supplementation, a practice which has been used to maintain animal productivity but which has led to the emergence of antibiotic resistant bacteria that are passed up the food chain to humans. Seaweed xylan-based animal foodstuffs have been developed to eliminate ruminant green-house gas emissions by gut methanogens in ruminant animals, contributing to atmospheric pollution. Biotransformation of pentosan polysulfate by the gut microbiome converts this semi-synthetic sulfated disease-modifying anti-osteoarthritic heparinoid drug to a prebiotic metabolite that promotes gut health, further extending the therapeutic profile and utility of this therapeutic molecule. Xylans are prominent dietary cereal components of the human diet which travel through the gastrointestinal tract as non-digested dietary fibre since the human genome does not contain xylanolytic enzymes. The gut microbiota however digest xylans as a food source. Xylo-oligosaccharides generated in this digestive process have prebiotic health-promoting properties. Engineered commensal probiotic bacteria also have been developed which have been engineered to produce growth factors and other bioactive factors. A xylan protein induction system controls the secretion of these compounds by the commensal bacteria which can promote gut health or, if these prebiotic compounds are transported by the vagal nervous system, may also regulate the health of linked organ systems via the gut–brain, gut–lung and gut–stomach axes. Dietary xylans are thus emerging therapeutic compounds warranting further study in novel disease prevention protocols. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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26 pages, 4178 KiB  
Review
Traditional Uses, Phytochemistry, and Pharmacological Properties of the Genus Blechnum—A Narrative Review
by Emmanuel Nyongesa Waswa, Felix Wambua Muema, Wyclif Ochieng Odago, Elizabeth Syowai Mutinda, Consolata Nanjala, Elijah Mbandi Mkala, Sarah Getachew Amenu, Shi-Xiong Ding, Jing Li and Guang-Wan Hu
Pharmaceuticals 2022, 15(7), 905; https://doi.org/10.3390/ph15070905 - 21 Jul 2022
Cited by 4 | Viewed by 3117
Abstract
Blechnum L. is a genus belonging to the Blechnaceae family with 236 accepted species that grow in intertropical, subtropical, and southern temperate regions. Several species of the genus have long been used in folk medicines to treat a broad spectrum of ailments, including [...] Read more.
Blechnum L. is a genus belonging to the Blechnaceae family with 236 accepted species that grow in intertropical, subtropical, and southern temperate regions. Several species of the genus have long been used in folk medicines to treat a broad spectrum of ailments, including typhoid, urinary infections, influenza, wounds, pulmonary complaints, blisters, boils, and antihelmintic-related complications. So far, about 91 chemical compounds have been isolated from different parts of 20 Blechnum species. Among these metabolites, phenolic compounds, sterols, and fatty acids are the main constituents. Modern pharmacological investigations revealed several isolated compounds and extracts to exhibit exceptional biological properties including the antioxidant, antimicrobial, anti-inflammatory, anticancer, insecticidal, antitrematocidal and wound healing. In various tests, both quercetin-7′,3′,4′-trimethoxy and phytol metabolites showed potential antioxidant and antitrematocidal properties, while ponasterone exhibited insecticidal activity. Despite having a broad range of traditional medicinal benefits and biological properties, understanding the scientific connotations based on the available data is still challenging. This article presents a comprehensive review of the traditional uses, phytochemical compounds, and pharmacological aspects of the Blechnum species. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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22 pages, 1605 KiB  
Review
Focusing on Future Applications and Current Challenges of Plant Derived Extracellular Vesicles
by Yuchen Wang, Junfeng Wang, Jinqian Ma, Yun Zhou and Rong Lu
Pharmaceuticals 2022, 15(6), 708; https://doi.org/10.3390/ph15060708 - 03 Jun 2022
Cited by 24 | Viewed by 4633
Abstract
Plant derived extracellular vesicles (EVs) are nano-sized membranous vesicles released by plant cells, which contain lipids, proteins, nucleic acids and specific pharmacologically active substances. They are safe, widely available and expediently extractive. They have gratifyingly biological activity against inflammation, cancer, bacteria and oxidative [...] Read more.
Plant derived extracellular vesicles (EVs) are nano-sized membranous vesicles released by plant cells, which contain lipids, proteins, nucleic acids and specific pharmacologically active substances. They are safe, widely available and expediently extractive. They have gratifyingly biological activity against inflammation, cancer, bacteria and oxidative aging, especially for the prevention or treatment of colitis, cancer, alcoholic liver, and COVID-19. In addition, as natural drug carriers, plant derived EVs have the potential to target the delivery of small molecule drugs and nucleic acid through oral, transdermal, injection. With the above advantages, plant derived EVs are expected to have excellent strong competitiveness in clinical application or preventive health care products in the future. We comprehensively reviewed the latest separation methods and physical characterization techniques of plant derived EVs, summarized the application of them in disease prevention or treatment and as a new drug carrier, and analyzed the clinical application prospect of plant derived EVs as a new drug carrier in the future. Finally, the problems hindering the development of plant derived EVs at present and consideration of the standardized application of them are discussed. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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Other

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16 pages, 7272 KiB  
Systematic Review
Unravelling Potential Health-Beneficial Properties of Corema album Phenolic Compounds: A Systematic Review
by Ana Sofia Cerquido, Martin Vojtek, Rita Ribeiro-Oliveira, Olga Viegas, Joana Beatriz Sousa, Isabel M. P. L. V. O. Ferreira and Carmen Diniz
Pharmaceuticals 2022, 15(10), 1231; https://doi.org/10.3390/ph15101231 - 08 Oct 2022
Cited by 1 | Viewed by 1741
Abstract
Corema (C.) album belongs to the family Ericaceae and can be found in the Iberian Peninsula, especially on the coastal areas facing the Atlantic coast. C. album berries have been used for centuries in traditional medicine. Recent studies have revealed that not only [...] Read more.
Corema (C.) album belongs to the family Ericaceae and can be found in the Iberian Peninsula, especially on the coastal areas facing the Atlantic coast. C. album berries have been used for centuries in traditional medicine. Recent studies have revealed that not only the berries but also the leaves have relevant antioxidant, antiproliferative, and anti-inflammatory properties, bringing this plant to the forefront of discussion. A systematic review of the literature was carried out to summarize the phenolic compounds and bioactive properties identified in C. album berries and leaves and to search for research gaps on this topic. The search was conducted in three electronic databases (PubMed, SCOPUS, and Web of Science) using PRISMA methodology. The inclusion criteria were the chemical compositions of the berries, leaves, or their extracts and their bioactive properties. The exclusion criteria were agronomic and archaeological research. The number of studies concerning phenolic compounds’ composition and the bioactive properties of C. album berries and leaves is still limited (11 articles). However, the variety of polyphenolic compounds identified make it possible to infer new insights into their putative mechanism of action towards the suppression of NF-kB transcription factor activation, the modulation of inflammatory mediators/enzymes, the induction of apoptosis, the modulation of mitogen activated protein kinase, cell cycle arrest, and the reduction of oxidative stress. These factors can be of major relevance concerning the future use of C. album as nutraceuticals, food supplements, or medicines. Nevertheless, more scientific evidence concerning C. album’s bioactivity is required. Full article
(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2022)
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