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Natural Bioactive Compounds from Fruits, Herbs, and Vegetables as Health Promoters

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 21916

Special Issue Editors

Department of Pharmaceutical Botany, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688 Krakow, Poland
Interests: plant biotechnology; phytochemistry; pharmaceutical botany; biochemistry
Special Issues, Collections and Topics in MDPI journals
Department of Pharmaceutical Botany, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688 Krakow, Poland
Interests: plant biotechnology, phytochemistry, pharmaceutical botany, HPLC analyses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products are a pool of metabolites with high structural diversity and various bioactivities. Plant-derived metabolites exhibit a wide range of properties, such as antioxidant, antimicrobial, immunostimulating, and antiproliferative. They can act as cardioprotective, neuroprotective agents or be conducive in diabetic and obesity therapy. Every day, humans consume a lot of bioactive compounds with food. Raw or low-processed foods are an especially good source of these metabolites.

The main aim of this Special Issue on “Natural Bioactive Compounds from Fruits, Herbs, and Vegetables as Health Promoters” is to present research and findings in health benefits connected with naturally derived compounds. Results proving the biological activity of isolated naturally derived compounds or extracts from fruits, herbs, and vegetables are particularly welcome. All studies on the mentioned activities (from in vitro tests to clinical trials) will be considered.

We look forward to receiving your contribution to this Special Issue. Original papers or review articles are welcome.

Dr. Inga Kwiecień
Dr. Agnieszka Szewczyk
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • natural products
  • bioactive effects
  • structure–-bioactivity relations
  • in vitro methods
  • in vivo tests
  • clinical investigations
  • health benefits

Published Papers (11 papers)

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Research

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19 pages, 1254 KiB  
Article
Shoot Cultures of Vitis vinifera (Vine Grape) Different Cultivars as a Promising Innovative Cosmetic Raw Material—Phytochemical Profiling, Antioxidant Potential, and Whitening Activity
by Marta Sharafan, Magdalena Anna Malinowska, Marta Kubicz, Paweł Kubica, Marin-Pierre Gémin, Cécile Abdallah, Manon Ferrier, Christophe Hano, Nathalie Giglioli-Guivarc’h, Elżbieta Sikora, Arnaud Lanoue and Agnieszka Szopa
Molecules 2023, 28(19), 6868; https://doi.org/10.3390/molecules28196868 - 29 Sep 2023
Cited by 2 | Viewed by 930
Abstract
The primary purpose of this work was the initiation and optimization of shoot cultures of different Vitis vinifera L. cultivars: cv. Chardonnay, cv. Hibernal, cv. Riesling, cv. Johanniter, cv. Solaris, cv. Cabernet Cortis, and cv. Regent. Cultures were maintained on 30-day growth cycles [...] Read more.
The primary purpose of this work was the initiation and optimization of shoot cultures of different Vitis vinifera L. cultivars: cv. Chardonnay, cv. Hibernal, cv. Riesling, cv. Johanniter, cv. Solaris, cv. Cabernet Cortis, and cv. Regent. Cultures were maintained on 30-day growth cycles using two media, Murashige and Skoog (MS) and Schenk and Hildebrandt (SH), with various concentrations of plant growth regulators. Tested media (‘W1’–‘W4’) contained varying concentrations of 6-benzylaminopurine (BA) in addition to indole-3-butyric acid (IBA) and 1-naphthaleneacetic acid (NAA). High performance liquid chromatography coupled with mass spectrometry (UPLC–MS) was used for metabolomic profiling. In all tested extracts, 45 compounds were identified (6 amino acids, 4 phenolic acids, 13 flavan-3-ols, 3 flavonols, and 19 stilbenoids). Principal component analysis (PCA) was performed to assess the influence of the genotype and medium on metabolic content. PCA showed that metabolic content was mainly influenced by genotype and to a lesser extent by medium composition. MS media variants induced the amino acid, procyanidin, and flavan-3-ol production. In addition, the antioxidant potential and anti-tyrosinase activity was measured spectrophotometrically. The studies on antioxidant activity clearly reveal very high efficiency in reducing free radicals in the tested extracts. The strongest tyrosinase inhibition capacity was proved for shoots cv. Hibernal cultured in SH medium and supplemented with NAA, with an inhibition of 17.50%. These studies show that in vitro cultures of V. vinifera cvs. can be proposed as an alternative source of plant material that can be potentially used in cosmetic industry. Full article
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11 pages, 1637 KiB  
Article
Inhibitory Potential of Different Bilberry (Vaccinium myrtillus L.) Extracts on Human Salivary α-Amylase
by Diana Karcheva-Bahchevanska, Mariana Nikolova and Ilia Iliev
Molecules 2023, 28(15), 5820; https://doi.org/10.3390/molecules28155820 - 02 Aug 2023
Viewed by 862
Abstract
Recently, consumer preferences for bilberries have increased markedly. This fact is probably related to their natural constituents, such as phenolic compounds including anthocyanins and tannins, as well as the vitamins and minerals they contain. Phenolic compounds are known for their numerous beneficial effects [...] Read more.
Recently, consumer preferences for bilberries have increased markedly. This fact is probably related to their natural constituents, such as phenolic compounds including anthocyanins and tannins, as well as the vitamins and minerals they contain. Phenolic compounds are known for their numerous beneficial effects on human health. Moreover, bilberry fruits have been shown to inhibit the activity of carbohydrate hydrolyzing enzymes, which can significantly decrease the postprandial increase in blood glucose levels. Thus, the aim of the present study is to investigate the inhibitory effect of Vaccinium myrtillus L. extracts on key enzyme α-amylase, linked to type 2 diabetes. No data have been published on the inhibitory properties of Vaccinium myrtillus L. fruits growing wild in Bulgaria against carbohydrate enzymes. Bilberry extracts were analyzed for total polyphenols, total anthocyanin content, antioxidant activity and their inhibitory properties against α-amylase. The contents of flavonols, anthocyanins and stilbenes were determined by HPLC analysis. The identified flavonols in the analyzed bilberry extracts were mainly represented by quercetin derivatives as rutinoside. The predominant anthocyanins for both aqueous and organic solvents were delphinidin-3-galactoside and malvidin-3-glucoside. The results revealed that bilberry extracts are effective inhibitors of α-amylase, with IC50 values from 20.8 to 194.8 μg GAE/mL. All the samples proved to have antioxidant activity measured by three different in vitro assays (FRAP, CUPRAC and DPPH). The inhibitory properties of V. myrtillus L. extracts may provide a new direction in the development and research of new pharmaceuticals for the suppression of postprandial hyperglycemia in diabetic patients. Full article
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19 pages, 2637 KiB  
Article
Yohimbine Alleviates Oxidative Stress and Suppresses Aerobic Cysteine Metabolism Elevated in the Rat Liver of High-Fat Diet-Fed Rats
by Małgorzata Iciek, Magdalena Górny, Magdalena Kotańska, Anna Bilska-Wilkosz, Marta Kaczor-Kamińska and Jacek Zagajewski
Molecules 2023, 28(5), 2025; https://doi.org/10.3390/molecules28052025 - 21 Feb 2023
Viewed by 1886
Abstract
Yohimbine is a small indole alkaloid derived from the bark of the yohimbe tree with documented biological activity, including anti-inflammatory, erectile dysfunction relieving, and fat-burning properties. Hydrogen sulfide (H2S) and sulfane sulfur-containing compounds are regarded as important molecules in redox regulation [...] Read more.
Yohimbine is a small indole alkaloid derived from the bark of the yohimbe tree with documented biological activity, including anti-inflammatory, erectile dysfunction relieving, and fat-burning properties. Hydrogen sulfide (H2S) and sulfane sulfur-containing compounds are regarded as important molecules in redox regulation and are involved in many physiological processes. Recently, their role in the pathophysiology of obesity and obesity-induced liver injury was also reported. The aim of the present study was to verify whether the mechanism of biological activity of yohimbine is related to reactive sulfur species formed during cysteine catabolism. We tested the effect of yohimbine at doses of 2 and 5 mg/kg/day administered for 30 days on aerobic and anaerobic catabolism of cysteine and oxidative processes in the liver of high-fat diet (HFD)-induced obese rats. Our study revealed that HFD resulted in a decrease in cysteine and sulfane sulfur levels in the liver, while sulfates were elevated. In the liver of obese rats, rhodanese expression was diminished while lipid peroxidation increased. Yohimbine did not influence sulfane sulfur and thiol levels in the liver of obese rats, however, this alkaloid at a dose of 5 mg decreased sulfates to the control level and induced expression of rhodanese. Moreover, it diminished hepatic lipid peroxidation. It can be concluded that HFD attenuates anaerobic and enhances aerobic cysteine catabolism and induces lipid peroxidation in the rat liver. Yohimbine at a dose of 5 mg/kg can alleviate oxidative stress and reduce elevated concentrations of sulfate probably by the induction of TST expression. Full article
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21 pages, 1697 KiB  
Article
In Vitro Cultures of Scutellaria brevibracteata subsp. subvelutina as a Source of Bioactive Phenolic Metabolites
by Inga Kwiecień, Aleksandra Łukaszyk, Natalizia Miceli, Maria Fernanda Taviano, Federica Davì, Elżbieta Kędzia and Halina Ekiert
Molecules 2023, 28(4), 1785; https://doi.org/10.3390/molecules28041785 - 14 Feb 2023
Cited by 3 | Viewed by 1436
Abstract
Some of the more than 350 Scutellaria species, such as S. baicalensis and S. lateriflora, have been used in traditional medicine and today play an important role in official phytotherapy. Other species have been less investigated, and their therapeutic potential is unknown. [...] Read more.
Some of the more than 350 Scutellaria species, such as S. baicalensis and S. lateriflora, have been used in traditional medicine and today play an important role in official phytotherapy. Other species have been less investigated, and their therapeutic potential is unknown. This is one of the few studies on Scutellaria brevibracteata subsp. subvelutina, and the first research of this species’ in vitro cultures. The aim of this study was to establish an in vitro culture and analyse its phytochemical profile and biological activity. In the methanolic extracts from biomass cultured on six solid Murashige and Skoog (MS) medium variants supplemented with different combinations of 6-benzylaminopurine (BAP) and 1-naphthaleneacetic acid (NAA) in the range 0.5–3 mg/L analysed by HPLC, the presence of specific flavonoids (baicalein, baicalin, wogonin, wogonoside, scutellarin, chrysin), phenylpropanoid glycosides (verbascoside, isoverbascoside), and phenolic acids (p-hydroxybenzoic, caffeic, ferulic, m-coumaric acids) was confirmed. The dominant metabolites were wogonoside and verbascoside with the highest content of 346 and 457 mg/100 g DW, respectively. Thus, the extract with the highest content of bioactive metabolites was selected for further research and subjected to evaluation of antioxidant and antimicrobial potential. The extract exhibited good free radical scavenging activity (IC50 = 0.92 ± 0.01 mg/mL) and moderate reducing power and chelating activity. The brine shrimp lethality bioassay proved its lack of biotoxicity. Antimicrobial activity was tested against sixteen strains of Gram-positive and Gram-negative bacteria and fungi. The strongest growth inhibitory activity was observed against Trichophyton tonsurans. Full article
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17 pages, 683 KiB  
Article
Metabolic Profiling of Inga Species with Antitumor Activity
by Nerilson M. Lima, Gagan Preet, Sara R. Marqui, Thaís de O. R. S. Falcoski, Geovana Navegante, Christiane P. Soares, Teresinha de Jesus A. S. Andrade, Felipe A. La Porta, Harinantenaina Liva R. Rakotondraie, Marcel Jaspars and Dulce H. S. Silva
Molecules 2022, 27(15), 4695; https://doi.org/10.3390/molecules27154695 - 22 Jul 2022
Viewed by 2004
Abstract
This work evaluated the metabolic profiling of Inga species with antitumor potential. In addition, we described the antigenotoxicity of polyphenols isolated from I. laurina and a proteomic approach using HepG2 cells after treatment with these metabolites. The in vitro cytotoxic activity against HepG2, [...] Read more.
This work evaluated the metabolic profiling of Inga species with antitumor potential. In addition, we described the antigenotoxicity of polyphenols isolated from I. laurina and a proteomic approach using HepG2 cells after treatment with these metabolites. The in vitro cytotoxic activity against HepG2, HT-29 and T98G cancer cell lines was investigated. The assessment of genotoxic damage was carried out through the comet assay. The ethanolic extract from I. laurina seeds was subjected to bioassay-guided fractionation and the most active fractions were characterized. One bioactive fraction with high cytotoxicity against HT-29 human colon cancer cells (IC50 = 4.0 µg mL−1) was found, and it was characterized as a mixture of p-hydroxybenzoic acid and 4-vinyl-phenol. The I. edulis fruit peel (IC50 = 18.6 µg mL−1) and I. laurina seed (IC50 = 15.2 µg mL−1) extracts had cytotoxic activity against the cell line T98G, and its chemical composition showed a variety of phenolic acids. The chemical composition of this species indicated a wide variety of aromatic acids, flavonoids, tannins, and carotenoids. The high concentration (ranging from 5% to 30%) of these polyphenols in the bioactive extract may be responsible for the antitumor potential. Regarding the proteomic approach, we detected proteins directly related to the elimination of ROS, DNA repair, expression of tumor proteins, and apoptosis. Full article
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17 pages, 1340 KiB  
Article
Synergistic Anti-Inflammatory Activity of Ginger and Turmeric Extracts in Inhibiting Lipopolysaccharide and Interferon-γ-Induced Proinflammatory Mediators
by Xian Zhou, Sualiha Afzal, Hans Wohlmuth, Gerald Münch, David Leach, Mitchell Low and Chun Guang Li
Molecules 2022, 27(12), 3877; https://doi.org/10.3390/molecules27123877 - 16 Jun 2022
Cited by 11 | Viewed by 4304
Abstract
This study aims to investigate the combined anti-inflammatory activity of ginger and turmeric extracts. By comparing the activities of individual and combined extracts in lipopolysaccharide and interferon-γ-induced murine RAW 264.7 cells, we demonstrated that ginger-turmeric combination was optimal at a specific ratio (5:2, [...] Read more.
This study aims to investigate the combined anti-inflammatory activity of ginger and turmeric extracts. By comparing the activities of individual and combined extracts in lipopolysaccharide and interferon-γ-induced murine RAW 264.7 cells, we demonstrated that ginger-turmeric combination was optimal at a specific ratio (5:2, w/w) in inhibiting nitric oxide, tumour necrosis factor and interleukin 6 with synergistic interaction (combination index < 1). The synergistic inhibitory effect on TNF was confirmed in human monocyte THP-1 cells. Ginger-turmeric combination (5:2, w/w) also upregulated nuclear factor erythroid 2–related factor 2 activity and heme oxygenase-1 protein expression. Additionally, 6-shogaol, 8-shogaol, 10-shogaol and curcumin were the leading compounds in reducing major proinflammatory mediators and cytokines, and a simplified compound combination of 6-s, 10-s and curcumin showed the greatest potency in reducing LPS-induced NO production. Our study provides scientific evidence in support of the combined use of ginger and turmeric to alleviate inflammatory processes. Full article
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22 pages, 2527 KiB  
Article
Biological Activity of Extracts of Red and Yellow Fruits of Cornus mas L.—An In Vitro Evaluation of Antioxidant Activity, Inhibitory Activity against α-Glucosidase, Acetylcholinesterase, and Binding Capacity to Human Serum Albumin
by Olha Dzydzan, Iryna Brodyak, Paulina Strugała-Danak, Angelika Strach, Alicja Z. Kucharska, Janina Gabrielska and Natalia Sybirna
Molecules 2022, 27(7), 2244; https://doi.org/10.3390/molecules27072244 - 30 Mar 2022
Cited by 6 | Viewed by 1837
Abstract
Although extracts are broadly used in order to support the treatment of numerous diseases, only in a limited number of cases is the process of applying and establishing their mechanisms of action scientifically analyzed. Fruits of Cornelian cherry are an abundant source of [...] Read more.
Although extracts are broadly used in order to support the treatment of numerous diseases, only in a limited number of cases is the process of applying and establishing their mechanisms of action scientifically analyzed. Fruits of Cornelian cherry are an abundant source of iridoids, anthocyanins, flavonols and phenolic acids. The aim of the present study was to evaluate the in vitro bioactivity of red and yellow Cornelian cherry fruits’ extracts. The biological potential of extracts, in a broad sense, involved antioxidant activity in relation to phosphatidylcholine liposomes, inhibitory ability against α-glucosidase and acetylcholinesterase enzymes, as well as interactions with human serum albumin. Studies showed that both extracts were more effective in protecting liposome membranes against free radicals produced by AAPH in an aqueous environment due to the fact that they can be better eliminated by the hydrophilic components of the extracts than those produced by UVB radiation. Extracts exhibited inhibitory activity against acetylcholinesterase and α-glucosidase, wherein loganic acid extract showed noncompetitive inhibition of the enzyme. Moreover, extracts binded to albumin mainly through hydrogen bonds and van der Waals forces. Taken together, red and yellow cherry fruits’ extracts exhibit diverse biological properties and can be exploited as a source of natural therapeutic agents. Full article
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Review

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25 pages, 2268 KiB  
Review
Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic Targets
by Wamidh H. Talib, Dima Awajan, Abdelrahim Alqudah, Razan Alsawwaf, Raha Althunibat, Mahmoud Abu AlRoos, Ala’a Al Safadi, Sharif Abu Asab, Rawan W. Hadi and Lina T. Al Kury
Molecules 2024, 29(6), 1373; https://doi.org/10.3390/molecules29061373 - 20 Mar 2024
Viewed by 461
Abstract
Epigallocatechin gallate (EGCG) is a catechin, which is a type of flavonoid found in high concentrations in green tea. EGCG has been studied extensively for its potential health benefits, particularly in cancer. EGCG has been found to exhibit anti-proliferative, anti-angiogenic, and pro-apoptotic effects [...] Read more.
Epigallocatechin gallate (EGCG) is a catechin, which is a type of flavonoid found in high concentrations in green tea. EGCG has been studied extensively for its potential health benefits, particularly in cancer. EGCG has been found to exhibit anti-proliferative, anti-angiogenic, and pro-apoptotic effects in numerous cancer cell lines and animal models. EGCG has demonstrated the ability to interrupt various signaling pathways associated with cellular proliferation and division in different cancer types. EGCG anticancer activity is mediated by interfering with various cancer hallmarks. This article summarize and highlight the effects of EGCG on cancer hallmarks and focused on the impacts of EGCG on these cancer-related hallmarks. The studies discussed in this review enrich the understanding of EGCG’s potential as a therapeutic tool against cancer, offering a substantial foundation for scientists and medical experts to advance scientific and clinical investigations regarding EGCG’s possibility as a potential anticancer treatment. Full article
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40 pages, 10678 KiB  
Review
The Therapeutic Value of Solanum Steroidal (Glyco)Alkaloids: A 10-Year Comprehensive Review
by Julien A. Delbrouck, Michael Desgagné, Christian Comeau, Kamal Bouarab, François Malouin and Pierre-Luc Boudreault
Molecules 2023, 28(13), 4957; https://doi.org/10.3390/molecules28134957 - 23 Jun 2023
Cited by 5 | Viewed by 2096
Abstract
Steroidal (glycol)alkaloids S(G)As are secondary metabolites made of a nitrogen-containing steroidal skeleton linked to a (poly)saccharide, naturally occurring in the members of the Solanaceae and Liliaceae plant families. The genus Solanum is familiar to all of us as a food source (tomato, potato, [...] Read more.
Steroidal (glycol)alkaloids S(G)As are secondary metabolites made of a nitrogen-containing steroidal skeleton linked to a (poly)saccharide, naturally occurring in the members of the Solanaceae and Liliaceae plant families. The genus Solanum is familiar to all of us as a food source (tomato, potato, eggplant), but a few populations have also made it part of their ethnobotany for their medicinal properties. The recent development of the isolation, purification and analysis techniques have shed light on the structural diversity among the SGAs family, thus attracting scientists to investigate their various pharmacological properties. This review aims to overview the recent literature (2012–2022) on the pharmacological benefits displayed by the SGAs family. Over 17 different potential therapeutic applications (antibiotic, antiviral, anti-inflammatory, etc.) were reported over the past ten years, and this unique review analyzes each pharmacological effect independently without discrimination of either the SGA’s chemical identity or their sources. A strong emphasis is placed on the discovery of their biological targets and the subsequent cellular mechanisms, discussing in vitro to in vivo biological data. The therapeutic value and the challenges of the solanum steroidal glycoalkaloid family is debated to provide new insights for future research towards clinical development. Full article
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57 pages, 1114 KiB  
Review
Dipsacus and Scabiosa Species—The Source of Specialized Metabolites with High Biological Relevance: A Review
by Ewa Skała and Agnieszka Szopa
Molecules 2023, 28(9), 3754; https://doi.org/10.3390/molecules28093754 - 27 Apr 2023
Cited by 1 | Viewed by 1861
Abstract
The genera Dipsacus L. and Scabiosa L. of the Caprifoliaceae family are widely distributed in Europe, Asia, and Africa. This work reviews the available literature on the phytochemical profiles, ethnomedicinal uses, and biological activities of the most popular species. These plants are rich [...] Read more.
The genera Dipsacus L. and Scabiosa L. of the Caprifoliaceae family are widely distributed in Europe, Asia, and Africa. This work reviews the available literature on the phytochemical profiles, ethnomedicinal uses, and biological activities of the most popular species. These plants are rich sources of many valuable specialized metabolites with beneficial medicinal properties, such as triterpenoid derivatives, iridoids, phenolic acids, and flavonoids. They are also sources of essential oils. The genus Dipsacus has been used for centuries in Chinese and Korean folk medicines to treat bone (osteoporosis) and joint problems (rheumatic arthritis). The Korean Herbal Pharmacopoeia and Chinese Pharmacopoeia include Dipsaci radix, the dried roots of D. asperoides C.Y.Cheng & T.M.Ai. In addition, S. comosa Fisch. ex Roem & Schult. and S. tschiliiensis Grunning are used in traditional Mongolian medicine to treat liver diseases. The current scientific literature data indicate that these plants and their constituents have various biological properties, including inter alia antiarthritic, anti-neurodegenerative, anti-inflammatory, antioxidant, anticancer, and antimicrobial activities; they have also been found to strengthen tendon and bone tissue and protect the liver, heart, and kidney. The essential oils possess antibacterial, antifungal, and insecticidal properties. This paper reviews the key biological values of Dipsacus and Scabiosa species, as identified by in vitro and in vivo studies, and presents their potential pharmacological applications. Full article
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11 pages, 931 KiB  
Review
Erucic Acid—Both Sides of the Story: A Concise Review on Its Beneficial and Toxic Properties
by Agnieszka Galanty, Marta Grudzińska, Wojciech Paździora and Paweł Paśko
Molecules 2023, 28(4), 1924; https://doi.org/10.3390/molecules28041924 - 17 Feb 2023
Cited by 6 | Viewed by 2929
Abstract
Erucic acid (EA) is monounsaturated fatty acid (22:1 n-9), synthesized in the seeds of many plants from the Brassicaceae family, with Brassica napus, B. rapa, or B. carinata considered as its richest source. As the compound has been blamed for the [...] Read more.
Erucic acid (EA) is monounsaturated fatty acid (22:1 n-9), synthesized in the seeds of many plants from the Brassicaceae family, with Brassica napus, B. rapa, or B. carinata considered as its richest source. As the compound has been blamed for the poisoning effect in Toxic Oil Syndrome, and some data indicated its cardiotoxicity to rats, EA has been for decades classified as toxic substance, the use of which should be avoided. However, the cardiac adverse effects of EA have not been confirmed in humans, and the experiments in animal models had many limitations. Thus, the aim of this review was to present the results of the so far published studies on both toxic, and pharmacological properties of EA, trying to answer the question on its future medicinal use. Despite the ambiguous and relatively small data on toxic and beneficial effects of EA it seems that the compound is worth investigating. Further research should be particularly directed at the verification EA toxicity, more in-depth studies on its neuroprotective and cytotoxic properties, but also its use in combination with other drugs, as well as its role as a drug carrier. Full article
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