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Phytochemicals from Aromatic and Medicinal Plants: From Identification to Biomedical Applications

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Plant Sciences".

Deadline for manuscript submissions: closed (15 April 2022) | Viewed by 44007

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Guest Editor
1. Department of Biology and Environment, School of Life Sciences and Environment ; Universidade de Trás-os-Montes e Alto Douro (UTAD), 5001-801 Vila Real, Portugal
2. Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB-UTAD), 5001-801 Vila Real, Portugal
Interests: cell biology and biochemistry; cell-based assays; evaluation of bioactivities of natural compounds; phytochemicals; nutraceuticals; nanoencapsulation
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Special Issue Information

Dear Colleagues,

Aromatic and medicinal plants play a very important socio-cultural and economic role, for many communities all over the world, beyond being a source of curative and preventive molecules. The use of plants for therapeutic purposes constitutes a valuable ethnopharmacological knowledge that brings a major challenge, which is the identification of bioactive molecules behind the attributed health promoting properties. Phytochemicals from aromatic and medicinal plants, such as phenolics, flavonoids, terpenoids, alkaloids, and others, have been described as nutraceuticals acting at several targets and exerting beneficial health effects. Considering the need to discover new pharmacologically active compounds, both the characterization and identification of plant phytochemicals are required, as well as the study of the relationship between structure and function using in vitro, in vivo or in silico models, with the aim to validate the bioactivity effectiveness. The biomedical potential of phytochemicals is vast, from skin care to cancer prevention, from nutraceutical supply to chronic disease amelioration and prevention; however, the efficient pharmacological effect requires effective targeting, bioavailability at biologically active sites and at effective concentrations, among other aspects.

This Special Issue aims to comprehensively highlight the newest discoveries in phytochemicals obtained from medicinal and aromatic plants, as well as their physiological and pharmacological roles, and to describe their biomedical application. In addition, new strategies to achieve bioavailability and efficacy of phytochemicals at target sites are welcome.

We cordially invite authors to contribute original articles, as well as reviews, that bring new insights into the potential biomedical application of phytochemicals from aromatic and medicinal plants in the prevention and treatment of various chronic diseases.

Prof. Dr. Amélia M. Silva
Guest Editor

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Keywords

  • phytochemicals
  • aromatic and medicinal plants
  • biomedical applications
  • pharmacological effect
  • nutraceutical
  • bioavailability
  • phytochemical delivery

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Published Papers (9 papers)

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Research

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23 pages, 4300 KiB  
Article
Effects of Sulforaphane-Induced Cell Death upon Repeated Passage of Either P-Glycoprotein-Negative or P-Glycoprotein-Positive L1210 Cell Variants
by Anna Bertova, Szilvia Kontar, Zoltan Polozsanyi, Martin Simkovic, Zuzana Rosenbergova, Martin Rebros, Zdena Sulova, Albert Breier and Denisa Imrichova
Int. J. Mol. Sci. 2022, 23(18), 10818; https://doi.org/10.3390/ijms231810818 - 16 Sep 2022
Cited by 2 | Viewed by 1867
Abstract
The expression of the membrane ABCB1 transporter in neoplastic cells is one of the most common causes of reduced sensitivity to chemotherapy. In our previous study, we investigated the effect of a single culture of ABCB1-negative (S) and ABCB1-positive variants of L1210 cells [...] Read more.
The expression of the membrane ABCB1 transporter in neoplastic cells is one of the most common causes of reduced sensitivity to chemotherapy. In our previous study, we investigated the effect of a single culture of ABCB1-negative (S) and ABCB1-positive variants of L1210 cells (R and T) in the presence of sulforaphane (SFN). We demonstrated that SFN induces the onset of autophagy more markedly in S cells than in R or T cells. In the current study, we focused on the effect of the repeated culture of S, R and T cells in SFN-containing media. The repeated cultures increased the onset of autophagy compared to the simple culture, mainly in S cells and to a lesser extent in R and T cells, as indicated by changes in the cellular content of 16 and 18 kDa fragments of LC3B protein or changes in the specific staining of cells with monodansylcadaverine. We conclude that SFN affects ABCB1-negative S cells more than ABCB1-positive R and T cells during repeated culturing. Changes in cell sensitivity to SFN appear to be related to the expression of genes for cell-cycle checkpoints, such as cyclins and cyclin-dependent kinases. Full article
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24 pages, 2593 KiB  
Article
The Systems of Naringenin with Solubilizers Expand Its Capability to Prevent Neurodegenerative Diseases
by Anna Stasiłowicz-Krzemień, Michał Gołębiewski, Anita Płazińska, Wojciech Płaziński, Andrzej Miklaszewski, Marcin Żarowski, Zofia Adamska-Jernaś and Judyta Cielecka-Piontek
Int. J. Mol. Sci. 2022, 23(2), 755; https://doi.org/10.3390/ijms23020755 - 11 Jan 2022
Cited by 15 | Viewed by 2714
Abstract
Background: Naringenin (NAR) is a flavonoid with excellent antioxidant and neuroprotective potential that is limited by its low solubility. Thus, solid dispersions with β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), hydroxypropylmethylcellulose (HPMC), and microenvironmental pH modifiers were prepared. Methods: The systems formation analysis was performed by [...] Read more.
Background: Naringenin (NAR) is a flavonoid with excellent antioxidant and neuroprotective potential that is limited by its low solubility. Thus, solid dispersions with β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), hydroxypropylmethylcellulose (HPMC), and microenvironmental pH modifiers were prepared. Methods: The systems formation analysis was performed by X-Ray Powder Diffraction (XRPD) and Fourier-transform infrared spectroscopy (FT-IR). Water solubility and dissolution rates were studied with a pH of 1.2 and 6.8. In vitro permeability through the gastrointestinal tract (GIT) and the blood-brain barrier (BBB) was assessed with the parallel artificial membrane permeability assay (PAMPA) assay. The antioxidant activity was studied with the 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and cupric ion reducing antioxidant capacity (CUPRAC) assays, while in vitro enzymes studies involved the inhibition of acetylcholinesterase, butyrylcholinesterase, and tyrosinase. For the most promising system, in silico studies were conducted. Results: NAR solubility was increased 458-fold by the solid dispersion NAR:HP-β-CD:NaHCO3 in a mass ratio of 1:3:1. The dissolution rate was elevated from 8.216% to 88.712% in a pH of 1.2 and from 11.644% to 88.843% in a pH of 6.8 (within 3 h). NAR GIT permeability, described as the apparent permeability coefficient, was increased from 2.789 × 10−6 cm s−1 to 2.909 × 10−5 cm s−1 in an acidic pH and from 1.197 × 10−6 cm s−1 to 2.145 × 10−5 cm s−1 in a basic pH. NAR BBB permeability was established as 4.275 × 10−6 cm s−1. The antioxidant activity and enzyme inhibition were also increased. Computational studies confirmed NAR:HP-β-CD inclusion complex formation. Conclusions: A significant improvement in NAR solubility was associated with an increase in its biological activity. Full article
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17 pages, 6430 KiB  
Article
Polyurethane Foam Rafts Supported In Vitro Cultures of Rindera graeca Roots for Enhanced Production of Rinderol, Potent Proapoptotic Naphthoquinone Compound
by Mateusz Kawka, Irena Bubko, Mirosława Koronkiewicz, Beata Gruber-Bzura, Konstantia Graikou, Ioanna Chinou, Małgorzata Jeziorek, Agnieszka Pietrosiuk and Katarzyna Sykłowska-Baranek
Int. J. Mol. Sci. 2022, 23(1), 56; https://doi.org/10.3390/ijms23010056 - 21 Dec 2021
Cited by 5 | Viewed by 2490
Abstract
Unique phytochemical profile of plants belonging to Boraginaceae family provides a prolific resource of lipophilic pigments from the group of naphthoquinone derivatives. To overcome low compound content, the major obstacle of plant-based production, immobilization of Rindera graeca roots in in vitro cultures was [...] Read more.
Unique phytochemical profile of plants belonging to Boraginaceae family provides a prolific resource of lipophilic pigments from the group of naphthoquinone derivatives. To overcome low compound content, the major obstacle of plant-based production, immobilization of Rindera graeca roots in in vitro cultures was implemented for efficient production of rinderol, novel furanonaphthoquinone derivative with anticancer properties. Chromatographic procedures revealed rinderol presence in extracts of all investigated root lines, derived both from root biomass and post-culture medium. Unexpectedly, in the second stage of the experiment, rinderol production was ceased in control, unmodified culture systems. On the contrary, roots immobilized on PUF rafts uniformly and stably produced rinderol, and its highest amount was noted for transformed root lines after 42 days of cultivation (222.98 ± 10.47 µg/flask). PUF occurred to be the main place of compound accumulation. Moreover, investigation of rinderol biological activity revealed its fast-acting cell death induction in HeLa cervical cancer cells at relatively low concentrations. Presented results revealed successful application of R. graeca roots immobilization on PUF rafts for production and in situ product removal of rinderol, novel lipophilic furanonaphthoquinone with suggested proapoptotic activity. Full article
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17 pages, 2582 KiB  
Article
Effects of Osthole on Inflammatory Gene Expression and Cytokine Secretion in Histamine-Induced Inflammation in the Caco-2 Cell Line
by Natalia K. Kordulewska, Justyna Topa, Dominika Rozmus and Beata Jarmołowska
Int. J. Mol. Sci. 2021, 22(24), 13634; https://doi.org/10.3390/ijms222413634 - 20 Dec 2021
Cited by 4 | Viewed by 2550
Abstract
Hyperactivity of the immune system in the gastrointestinal tract leads to the development of chronic, inflammation-associated disorders. Such diseases, including inflammatory bowel disease, are not completely curable, but the specific line of treatment may reduce its symptoms. However, the response to treatment varies [...] Read more.
Hyperactivity of the immune system in the gastrointestinal tract leads to the development of chronic, inflammation-associated disorders. Such diseases, including inflammatory bowel disease, are not completely curable, but the specific line of treatment may reduce its symptoms. However, the response to treatment varies among patients, creating a necessity to uncover the pathophysiological basis of immune-mediated diseases and apply novel therapeutic strategies. The present study describes the anti-inflammatory properties of osthole during histamine-induced inflammation in the intestinal Caco-2 cell line. Osthole reduced the secretion of cytokines (CKs) and the expression level of inflammation-associated genes, which were increased after a histamine treatment. We have shown that the secretion of pro-inflammatory CKs (IL-1β, IL-6, IL-8, and TNF-α) during inflammation may be mediated by NFκB, and, after osthole treatment, this signaling pathway was disrupted. Our results suggest a possible role for osthole in the protection against inflammation in the gastrointestinal tract; thus, osthole may be considered as an anti-inflammatory modulator. Full article
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20 pages, 2908 KiB  
Article
Identification of Salicylates in Willow Bark (Salix Cortex) for Targeting Peripheral Inflammation
by Kyriaki Antoniadou, Corinna Herz, Nguyen Phan Khoi Le, Verena Karolin Mittermeier-Kleßinger, Nadja Förster, Matthias Zander, Christian Ulrichs, Inga Mewis, Thomas Hofmann, Corinna Dawid and Evelyn Lamy
Int. J. Mol. Sci. 2021, 22(20), 11138; https://doi.org/10.3390/ijms222011138 - 15 Oct 2021
Cited by 9 | Viewed by 3113
Abstract
Salix cortex-containing medicine is used against pain conditions, fever, headaches, and inflammation, which are partly mediated via arachidonic acid-derived prostaglandins (PGs). We used an activity-guided fractionation strategy, followed by structure elucidation experiments using LC-MS/MS, CD-spectroscopy, and 1D/2D NMR techniques, to identify the compounds [...] Read more.
Salix cortex-containing medicine is used against pain conditions, fever, headaches, and inflammation, which are partly mediated via arachidonic acid-derived prostaglandins (PGs). We used an activity-guided fractionation strategy, followed by structure elucidation experiments using LC-MS/MS, CD-spectroscopy, and 1D/2D NMR techniques, to identify the compounds relevant for the inhibition of PGE2 release from activated human peripheral blood mononuclear cells. Subsequent compound purification by means of preparative and semipreparative HPLC revealed 2-O-acetylsalicortin (1), 3-O-acetylsalicortin (2), 2-O-acetylsalicin (3), 2,6-O-diacetylsalicortin (4), lasiandrin (5), tremulacin (6), and cinnamrutinose A (7). In contrast to 3 and 7, compounds 1, 2, 4, 5, and 6 showed inhibitory activity against PGE2 release with different potencies. Polyphenols were not relevant for the bioactivity of the Salix extract but salicylates, which degrade to, e.g., catechol, salicylic acid, salicin, and/or 1-hydroxy-6-oxo-2-cycohexenecarboxylate. Inflammation presents an important therapeutic target for pharmacological interventions; thus, the identification of relevant key drugs in Salix could provide new prospects for the improvement and standardization of existing clinical medicine. Full article
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16 pages, 3740 KiB  
Article
Anti-Allergic and Anti-Inflammatory Effects of Neferine on RBL-2H3 Cells
by Kuan-Ming Chiu, Yen-Ling Hung, Su-Jane Wang, Yi-Ju Tsai, Nan-Lin Wu, Cher-Wei Liang, Der-Chen Chang and Chi-Feng Hung
Int. J. Mol. Sci. 2021, 22(20), 10994; https://doi.org/10.3390/ijms222010994 - 12 Oct 2021
Cited by 22 | Viewed by 4102
Abstract
Mast cells play a very important role in skin allergy and inflammation, including atopic dermatitis and psoriasis. In the past, it was found that neferine has anti-inflammatory and anti-aging effects on the skin, but its effect on mast cells has not yet been [...] Read more.
Mast cells play a very important role in skin allergy and inflammation, including atopic dermatitis and psoriasis. In the past, it was found that neferine has anti-inflammatory and anti-aging effects on the skin, but its effect on mast cells has not yet been studied in detail. In this study, we used mast cells (RBL-2H3 cells) and mouse models to study the anti-allergic and inflammatory effects of neferine. First, we found that neferine inhibits the degranulation of mast cells and the expression of cytokines. In addition, we observed that when mast cells were stimulated by A23187/phorbol 12-myristate-13-acetate (PMA), the elevation of intracellular calcium was inhibited by neferine. The phosphorylation of the MAPK/NF-κB pathway is also reduced by pretreatment of neferine. The results of in vivo studies show that neferine can improve the appearance of dermatitis and mast cell infiltration caused by dinitrochlorobenzene (DNCB). Moreover, the expressions of barrier proteins in the skin are also restored. Finally, it was found that neferine can reduce the scratching behavior caused by compound 48/80. Taken together, our results indicate that neferine is a very good anti-allergic and anti-inflammatory natural product. Its effect on mast cells contributes to its pharmacological mechanism. Full article
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13 pages, 8215 KiB  
Article
Bioactive Phytochemicals from Mulberry: Potential Anti-Inflammatory Effects in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages
by Dahae Lee, Seoung Rak Lee, Ki Sung Kang and Ki Hyun Kim
Int. J. Mol. Sci. 2021, 22(15), 8120; https://doi.org/10.3390/ijms22158120 - 29 Jul 2021
Cited by 13 | Viewed by 3556
Abstract
The fruits of the mulberry tree (Morus alba L.), known as white mulberry, have been consumed in various forms, including tea, beverages, and desserts, worldwide. As part of an ongoing study to discover bioactive compounds from M. alba fruits, the anti-inflammatory effect [...] Read more.
The fruits of the mulberry tree (Morus alba L.), known as white mulberry, have been consumed in various forms, including tea, beverages, and desserts, worldwide. As part of an ongoing study to discover bioactive compounds from M. alba fruits, the anti-inflammatory effect of compounds from M. alba were evaluated in lipopolysaccharide (LPS)-stimulated mouse RAW 264.7 macrophages. Phytochemical analysis of the ethanol extract of the M. alba fruits led to the isolation of 22 compounds. Among the isolated compounds, to the best of our knowledge, compounds 1, 3, 5, 7, 11, 12, and 14–22 were identified from M. alba fruits for the first time in this study. Inhibitory effects of 22 compounds on the production of the nitric oxide (NO) known as a proinflammatory mediator in LPS-stimulated RAW 264.7 macrophages were evaluated using NO assays. Western blot analysis was performed to evaluate the anti-inflammatory effects of cyclo(L-Pro-L-Val) (5). We evaluated whether the anti-inflammatory effects of cyclo(L-Pro-L-Val) (5) following LPS stimulation in RAW 264.7 macrophages occurred because of phosphorylation of IκB kinase alpha (IKKα), IκB kinase beta (IKKβ), inhibitor of kappa B alpha (IκBα), nuclear factor kappa B (NF-κB) and activations of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Cyclo(L-Pro-L-Val) (5) significantly suppressed phosphorylations of IKKα, IKKβ, IκBα, and NF-κB and activations of iNOS and COX-2 in a concentration-dependent manner. Taken together, these results indicate that cyclo(L-Pro-L-Val) (5) can be considered a potential therapeutic agent for the treatment of inflammation-associated disorders. Full article
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Review

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29 pages, 2001 KiB  
Review
Plant-Derived Antioxidants: Significance in Skin Health and the Ageing Process
by Monika Michalak
Int. J. Mol. Sci. 2022, 23(2), 585; https://doi.org/10.3390/ijms23020585 - 6 Jan 2022
Cited by 130 | Viewed by 17327
Abstract
Natural substances have traditionally been used in skin care for centuries. There is now an ongoing search for new natural bioactives that not only promote skin health but also protect the skin against various harmful factors, including ultraviolet radiation and free radicals. Free [...] Read more.
Natural substances have traditionally been used in skin care for centuries. There is now an ongoing search for new natural bioactives that not only promote skin health but also protect the skin against various harmful factors, including ultraviolet radiation and free radicals. Free radicals, by disrupting defence and restoration mechanisms, significantly contribute to skin damage and accelerate ageing. Natural compounds present in plants exhibit antioxidant properties and the ability to scavenge free radicals. The increased interest in plant chemistry is linked to the growing interest in plant materials as natural antioxidants. This review focuses on aromatic and medicinal plants as a source of antioxidant substances, such as polyphenols, tocopherols, carotenoids, ascorbic acid, and macromolecules (including polysaccharides and peptides) as well as components of essential oils, and their role in skin health and the ageing process. Full article
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17 pages, 2316 KiB  
Review
Natural Phytochemicals Derived from Gymnosperms in the Prevention and Treatment of Cancers
by Tayyebeh Ghaffari, Joo-Hyun Hong, Solmaz Asnaashari, Safar Farajnia, Abbas Delazar, Hamed Hamishehkar and Ki Hyun Kim
Int. J. Mol. Sci. 2021, 22(12), 6636; https://doi.org/10.3390/ijms22126636 - 21 Jun 2021
Cited by 11 | Viewed by 4582
Abstract
The incidence of various types of cancer is increasing globally. To reduce the critical side effects of cancer chemotherapy, naturally derived compounds have been considered for cancer treatment. Gymnosperms are a group of plants found worldwide that have traditionally been used for therapeutic [...] Read more.
The incidence of various types of cancer is increasing globally. To reduce the critical side effects of cancer chemotherapy, naturally derived compounds have been considered for cancer treatment. Gymnosperms are a group of plants found worldwide that have traditionally been used for therapeutic applications. Paclitaxel is a commercially available anticancer drug derived from gymnosperms. Other natural compounds with anticancer activities, such as pinostrobin and pinocembrin, are extracted from pine heartwood, and pycnogenol and enzogenol from pine bark. Gymnosperms have great potential for further study for the discovery of new anticancer compounds. This review aims to provide a rational understanding and the latest developments in potential anticancer compounds derived from gymnosperms. Full article
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