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Phytochemicals and Antioxidant, Anti-inflammatory and Cytotoxic Properties

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

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 18406

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Dr. Izabela Grzegorczyk-Karolak

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Department of Biology and Pharmaceutical Botany, Medical University of Lodz, 90-151 Lodz, Poland
Interests: natural compounds; phytochemistry; plant in vitro culture; polyphenols; methods of determination of antioxidant activity; phytotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Plants contain complex mixtures of secondary metabolites which have broad health benefits for humans. According to the WHO, 65–80% of the world’s population in developing countries uses plants for primary healthcare. The health-protective effects are mainly due to an antioxidant and anti-inflammatory activity exerted by phytochemicals and thus their role in protection against oxidative stress and its related diseases, such as inflammation, cardiovascular diseases, aging-related disorders or cancer. Although a great number of natural bioactive products have already been isolated and investigated, nature is still an endless source of medical drugs that are waiting to be discovered.

The aim of this Special Issue is to collect the reviews and original articles addressing current knowledge of bioactive plant products of antioxidant, anti-inflammatory and cytotoxic activity. The results of antioxidant, anti-inflammatory, and cytotoxic activity studies documented in vitro and in vivo, will be appreciated. As for many bioactive compounds, there is a lack of knowledge of their molecular targets, special emphasis is given to the submissions of research models with biomolecular experiments. I also encourage articles describing the identification of the molecules with antioxidant, anti-inflammatory and cytotoxic activity, their biochemical characterization and structure-activity relationships are welcome.

Substances without clear ingredients, such as complex prescriptions, crude extracts, and herbal mixtures, will not be considered.

Dr. Izabela Grzegorczyk-Karolak
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
medicinal plant
antioxidants
anticancer/antiproliferative activity
anti-inflammatory activity
chemical identification of plant compounds
molecular targets
structure-bioactivity relations
chemistry and mechanisms of action

Published Papers (10 papers)

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Research

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17 pages, 6160 KiB

Open AccessArticle

Isolation of High-Purity Betanin from Red Beet and Elucidation of Its Antioxidant Activity against Peroxynitrite: An in vitro Study

by Yasuko Sakihama, Takashi Kato, Sopanat Sawatdee, Yo Yakushi, Junichi Asano, Hiroyo Hayashi, Yuya Goto, Makoto Hashimoto and Yasuyuki Hashidoko

Int. J. Mol. Sci. 2023, 24(20), 15411; https://doi.org/10.3390/ijms242015411 - 21 Oct 2023

Viewed by 1045

Abstract

Reactive oxygen species and reactive nitrogen species (RNS) are damaging for many biomolecules. Peroxynitrite (ONOO⁻) is the most toxic molecular species among RNS. Betalains are known to possess ONOO⁻ scavenging ability. Betanin, a betalain isolated from red beet, possesses antioxidant, anti-inflammatory, and antitumor activities; however, detailed studies of this isolated pigment have not been conducted, owing to its instability under physiological conditions. This study aimed to isolate highly purified betanin from red beetroots using an improved purification method involving deproteinization and citric acid co-precipitation and evaluated its antioxidant activities. The purified betanin thus obtained had a significantly lower isobetanin content than the commercially available betanin dyes. The antioxidant activity of purified betanin examined in the 2,2-diphenyl-1-picrylhydrazyl assay, the direct ONOO⁻ reaction, ONOO⁻-dependent DNA damage, and lipid peroxidation reactions revealed that betanin possessed higher antioxidant capacity than general antioxidants such as ascorbic acid and quercetin. Furthermore, betanin showed indirect and direct cytoprotective effects against H₂O₂ and ONOO⁻ cytotoxicity, respectively, in cultured mouse fibroblasts. To the best of our knowledge, this is the first study to demonstrate the cytoprotective effects of betanin against ONOO⁻ toxicity. The highly purified betanin obtained in this study will aid in further exploring its physiological functions. Full article

(This article belongs to the Special Issue Phytochemicals and Antioxidant, Anti-inflammatory and Cytotoxic Properties)

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19 pages, 4224 KiB

Open AccessArticle

BFNB Enhances Hair Growth in C57BL/6 Mice through the Induction of EGF and FGF7 Factors and the PI3K-AKT-β-Catenin Pathway

by Salvador Pérez-Mora, Juan Ocampo-López, María del Consuelo Gómez-García and David Guillermo Pérez-Ishiwara

Int. J. Mol. Sci. 2023, 24(15), 12110; https://doi.org/10.3390/ijms241512110 - 28 Jul 2023

Cited by 2 | Viewed by 2182

Abstract

The objective of this study was to investigate the potential effects of a formulation derived from the bioactive fraction of nanostructured Bacopa procumbens (BFNB) on the promotion of hair growth in C57BL/6 mice. The characterization of the follicular phases and histomorphological analysis showed that the topical application of the formulation for 15 days significantly increased pigmentation and hair growth on the dorsum and head of the mice. Additionally, an acceleration of the follicular cycle phases was observed, along with an increase in the number of follicles, hair length, and diameter, compared to mice treated with minoxidil. In silico analysis and molecular characterization demonstrated that BFNB enhances the expression of epidermal growth factor (EGF) and fibroblast growth factor 7 (FGF7), activating the PI3K-AKT-β-catenin signaling pathway, as well as the expression of PCNA, KI-67, Cyclin D1, and Cyclin E, regulating the cell cycle and cell proliferation, crucial events for hair regeneration. Our results strongly suggest the utility of BFNB as a therapeutic alternative to stimulate hair growth and promote hair health. Full article

(This article belongs to the Special Issue Phytochemicals and Antioxidant, Anti-inflammatory and Cytotoxic Properties)

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36 pages, 11023 KiB

Open AccessArticle

Paeonia peregrina Mill Petals as a New Source of Biologically Active Compounds: Chemical Characterization and Skin Regeneration Effects of the Extracts

by Tatjana Marković, Natalija Čutović, Tamara Carević, Uroš Gašić, Dejan Stojković, Jingqi Xue and Aleksandra Jovanović

Int. J. Mol. Sci. 2023, 24(14), 11764; https://doi.org/10.3390/ijms241411764 - 21 Jul 2023

Cited by 3 | Viewed by 1343

Abstract

Paeonia peregrina Mill. is a perennial herbaceous plant species, known for the medicinal value of all of its plant parts, although the chemical composition of the petals is unknown. This study aimed to determine the chemical fingerprint of the petals and also establish the optimal extraction parameters, extraction medium, and extraction method for petals collected from different localities in Serbia. The optimization was performed in order to acquire extracts that are rich in the contents of total polyphenol content (TPC) and total flavonoid content (TFC), and also exhibit strong antioxidant activity. In addition, the influence of the extracts on several human skin pathogens was evaluated, as well as their ability to aid wound closure and act as anti-inflammatory agents. Both the extraction medium and the applied technique significantly influenced the skin-beneficial biological activities, while methanol proved to be a more favorable extraction medium. In conclusion, the extraction conditions that yielded the extract with the richest phenolic content with satisfactory biological potential varied between the assays, while the most promising locality in Serbia for the collection of P. peregrina petals was Pančevo (South Banat). Full article

(This article belongs to the Special Issue Phytochemicals and Antioxidant, Anti-inflammatory and Cytotoxic Properties)

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21 pages, 4302 KiB

Open AccessArticle

Extraction Optimization, Characterization and Biological Activities of Polysaccharide Extracts from Nymphaea hybrid

by Hui-Min Liu, Wei Tang, Sheng-Nan Lei, Yun Zhang, Ming-Yan Cheng, Qing-Lei Liu and Wei Wang

Int. J. Mol. Sci. 2023, 24(10), 8974; https://doi.org/10.3390/ijms24108974 - 18 May 2023

Cited by 5 | Viewed by 1551

Abstract

In this study, polysaccharide–rich Nymphaea hybrid extracts (NHE) were obtained using the ultrasound-assisted cellulase extraction (UCE) method optimized by response surface methodology (RSM). The structural properties and thermal stability of NHE were characterized by Fourier-transform infrared (FT–IR), high–performance liquid chromatography (HPLC) and thermogravimetry–derivative thermogravimetry (TG–DTG) analysis, respectively. Moreover, the bioactivities of NHE, including the antioxidant, anti–inflammatory, whitening and scratch healing activities were evaluated by different in vitro assays. NHE conveyed a good ability to scavenge against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and inhibit the hyaluronidase activity. NHE can effectively protect the HaCaT cells against oxidative damage by inhibiting the intracellular reactive oxygen species (ROS) production in the H₂O₂ stimulation assays and promoting the proliferation and migration in the scratch assays. In addition, NHE was proven to inhibit melanin production in B16 cells. Collectively, the above results seem to be the evidence needed to promote the potential of NHE to be regarded as a new functional raw material in the cosmetics or food industries. Full article

(This article belongs to the Special Issue Phytochemicals and Antioxidant, Anti-inflammatory and Cytotoxic Properties)

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16 pages, 5048 KiB

Open AccessArticle

Red Ginseng Improves D-galactose-Induced Premature Ovarian Failure in Mice Based on Network Pharmacology

by Zijing Shang, Meiling Fan, Jingtian Zhang, Zi Wang, Shuang Jiang and Wei Li

Int. J. Mol. Sci. 2023, 24(9), 8210; https://doi.org/10.3390/ijms24098210 - 4 May 2023

Cited by 3 | Viewed by 1929

Abstract

In this study, we evaluated the ameliorative effect and molecular mechanism of red ginseng (Panax ginseng C.A. Meyer) extract (RGE) on D-galactose (D-gal)-induced premature ovarian failure (POF) using network pharmacology analysis. Ginsenosides are important active ingredients in ginseng, which also contains some sugar and amino acid derivatives. We aimed to determine the key proteins through which RGE regulates POF. In this work, we retrieved and screened for active ingredients in ginseng and the corresponding POF disease targets in multiple databases. A PPI network of genes was constructed in the STRING database and core targets were screened using topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted in R software. Finally, molecular docking was conducted to validate the results. Female ICR mice were used to establish a POF mouse model for in vivo experiments. Serum levels of relevant estrogens were determined using ELISA and expression levels of relevant proteins in ovarian tissues were detected using immunofluorescence and western blot analysis. Network pharmacology analysis predicted that PI3K, Akt, Bax, Bcl-2, p16, and other proteins were highly correlated with POF and RGE. The results clearly showed that RGE could increase estradiol (E2) and lower follicle-stimulating hormone (FSH) levels in D-gal-fed mice. RGE restored the expression levels of related proteins by reducing Nrf2-mediated oxidative stress, PI3K/Akt-mediated apoptosis, and senescence signaling pathways. Overall, RGE has the potential to prevent and treat POF and is likely to be a promising natural protector of the ovaries. Full article

(This article belongs to the Special Issue Phytochemicals and Antioxidant, Anti-inflammatory and Cytotoxic Properties)

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18 pages, 6010 KiB

Open AccessArticle

Anti-Cancer Effects of Oxygen-Atom-Modified Derivatives of Wasabi Components on Human Leukemia Cells

by Jui-Feng Lin, Chih-Wen Chi, Yu-Chuen Huang, Tung-Hu Tsai and Yu-Jen Chen

Int. J. Mol. Sci. 2023, 24(7), 6823; https://doi.org/10.3390/ijms24076823 - 6 Apr 2023

Viewed by 1475

Abstract

1-Isothiocyanato-6-(methylsulfinyl)-hexanate (6-MITC) is a natural compound found in Wasabia japonica. The synthetic derivatives 1-Isothiocyanato-6-(methylsulfenyl)-hexane (I7447) and 1-Isothiocyanato-6-(methylsulfonyl)-hexane (I7557) were obtained from 6-MITC by deleting and adding an oxygen atom to the sulfone group, respectively. We previously demonstrated that extensive mitotic arrest, spindle multipolarity, and cytoplasmic vacuole accumulation were induced by 6-MITC and inhibited the viability of human chronic myelogenous leukemia K562 cells. In this study, we examined the anti-cancer effects of 6-MITC derivatives on human chronic myelogenous leukemia (CML) cells. Autophagy was identified as the formation of autophagosomes with double-layered membranes using transmission electron microscopy. Cell cycle and differentiation were analyzed using flow cytometry. Apoptosis was detected by annexin V staining. After treatment with I7447 and I7557, the G2/M phase of cell cycle arrest was revealed. Cell death can be induced by a distinct mechanism (the simultaneous occurrence of autophagy and aberrant mitosis). The expression levels of acridine orange were significantly affected by lysosomal inhibitors. The natural wasabi component, 6-MITC, and its synthetic derivatives have similar effects on human chronic myelogenous leukemia cells and may be developed as novel therapeutic agents against leukemia. Full article

(This article belongs to the Special Issue Phytochemicals and Antioxidant, Anti-inflammatory and Cytotoxic Properties)

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18 pages, 2740 KiB

Open AccessArticle

In Vitro Evaluation of Antioxidant and Protective Potential of Kombucha-Fermented Black Berry Extracts against H₂O₂-Induced Oxidative Stress in Human Skin Cells and Yeast Model

by Aleksandra Ziemlewska, Martyna Zagórska-Dziok, Zofia Nizioł-Łukaszewska, Patrycja Kielar, Mateusz Mołoń, Dariusz Szczepanek, Ireneusz Sowa and Magdalena Wójciak

Int. J. Mol. Sci. 2023, 24(5), 4388; https://doi.org/10.3390/ijms24054388 - 23 Feb 2023

Cited by 7 | Viewed by 2278

Abstract

The fruits of R. nigrum L., A. melanocarpa Michx., and V. myrtillus L. are well-known natural plant materials with proven antioxidant activity. This work attempts to compare the antioxidant properties of extracts of these plants and ferments obtained during their fermentation using a consortium of microorganisms referred to as kombucha. As part of the work, a phytochemical analysis of extracts and ferments was carried out using the UPLC-MS method and the content of the main components was determined. The antioxidant properties of the tested samples and their cytotoxicity were assessed with the use of DPPH and ABTS radicals. The protective effect against hydrogen peroxide-induced oxidative stress was also assessed. The possibility of inhibiting the increase in the intracellular level of reactive oxygen species was carried out on both human skin cells (keratinocytes and fibroblasts) and the yeast Saccharomyces cerevisiae (wild-type strains and sod1Δ deletion mutants). The conducted analyses showed that the ferments obtained are characterized by a greater variety of biologically active compounds; in most cases they do not cause a cytotoxic effect, show strong antioxidant properties, and can reduce oxidative stress in both human and yeast cells. This effect depends on the concentration used and the fermentation time. The results obtained indicate that the tested ferments can be considered as an extremely valuable raw material protecting cells against the negative effects of oxidative stress. Full article

(This article belongs to the Special Issue Phytochemicals and Antioxidant, Anti-inflammatory and Cytotoxic Properties)

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23 pages, 3998 KiB

Open AccessArticle

Research on the Electron Structure and Antimicrobial Properties of Mandelic Acid and Its Alkali Metal Salts

by Renata Świsłocka, Grzegorz Świderski, Justyna Nasiłowska, Barbara Sokołowska, Adrian Wojtczak and Włodzimierz Lewandowski

Int. J. Mol. Sci. 2023, 24(4), 3078; https://doi.org/10.3390/ijms24043078 - 4 Feb 2023

Cited by 6 | Viewed by 1580

Abstract

This article investigated the structure, and the spectroscopic and antimicrobial properties of mandelic acid and its alkali metal salts. The electron charge distribution and aromaticity in the analyzed molecules were investigated using molecular spectroscopy methods (FT-IR, FT-Raman, ¹H NMR, and ¹³C NMR) and theoretical calculations (structure, NBO, HOMO, LUMO, energy descriptors, and theoretical IR and NMR spectra). The B3LYP/6-311++G(d,p) method was used in the calculations. The antimicrobial activities of mandelic acid and its salt were tested against six bacteria: Gram-positive Listeria monocytogenes ATCC 13932, Staphylococcus aureus ATCC 25923, Bacillus subtilis ATCC 6633, and Loigolactobacillus backii KKP 3566; Gram-negative Escherichia coli ATCC 25922 and Salmonella Typhimurium ATCC 14028, as well as two yeast species, Rhodotorulla mucilaginosa KKP 3560 and Candida albicans ATCC 10231. Full article

(This article belongs to the Special Issue Phytochemicals and Antioxidant, Anti-inflammatory and Cytotoxic Properties)

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19 pages, 2944 KiB

Open AccessArticle

Protective Effects of Arbutus unedo L. Honey in the Alleviation of Irinotecan-Induced Cytogenetic Damage in Human Lymphocytes—An In Vitro Study

by Andreja Jurič, Irena Brčić Karačonji, Uroš Gašić, Dušanka Milojković Opsenica, Saša Prđun, Dragan Bubalo, Dražen Lušić, Nada Vahčić and Nevenka Kopjar

Int. J. Mol. Sci. 2023, 24(3), 1903; https://doi.org/10.3390/ijms24031903 - 18 Jan 2023

Cited by 2 | Viewed by 1966

Abstract

Strawberry tree (Arbutus unedo L.) honey (STH) has been used since ancient times as a folk medicine remedy, especially in certain Mediterranean countries. This honey, rich in phenolic content, is well recognized for its antioxidant, anti-inflammatory, and antimicrobial activities, and is used for the treatment of skin lesions as well as gastrointestinal and respiratory disorders. This study investigated whether STH alleviates genome damage in human peripheral blood lymphocytes produced by the cytotoxic drug irinotecan. The phenolic profile of STH was previously estimated by ultra-high-performance liquid chromatography coupled to a linear ion trap–Orbitrap hybrid mass spectrometer. The effects of STH were evaluated at three concentrations (1×, 5×, and 10×), based on the daily consumption of the honey by an adult person. After 2 h of in vitro exposure, standard lymphocyte cultures for the analysis of chromosome aberrations and the cytokinesis-block micronucleus cytome assay were established. Our results demonstrate that STH offered remarkable geno- and cytoprotection when administered with irinotecan. These findings are relevant for drawing preliminary conclusions regarding the in vitro safety of the tested honey. However, further studies are needed with the application of more complex experimental models. Full article

(This article belongs to the Special Issue Phytochemicals and Antioxidant, Anti-inflammatory and Cytotoxic Properties)

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Review

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38 pages, 2367 KiB

Open AccessReview

The Genus Cuphea P. Browne as a Source of Biologically Active Phytochemicals for Pharmaceutical Application and Beyond—A Review

by Danuta Sobolewska, Klaudia Michalska, Dagmara Wróbel-Biedrawa, Karolina Grabowska, Aleksandra Owczarek-Januszkiewicz, Monika Anna Olszewska and Irma Podolak

Int. J. Mol. Sci. 2023, 24(7), 6614; https://doi.org/10.3390/ijms24076614 - 1 Apr 2023

Viewed by 1746

Abstract

Cuphea P. Browne (Lythraceae) is a monophyletic taxon comprising some 240–260 species that grow wild in the warm, temperate, and tropical regions of South and Central America and the southern part of North America. They have been valued as traditional medicinal remedies for numerous indications, including treating wounds, parasitic infections, hypertension, digestive disorders, cough, rheumatism, and pain. Modern pharmacological research provides data that support many of these traditional uses. Such a wide array of medicinal applications may be due to the exceptionally rich phytochemical profile of these plants, which includes bioactive compounds classified into various metabolite groups, such as polyphenols, triterpenes, alkaloids, and coumarins. Furthermore, Cuphea seed oils, containing medium-chain fatty acids, are of increasing interest in various industries as potential substitutes for coconut and palm oils. This review aims to summarize the results of phytochemical and pharmacological studies on Cuphea plants, with a particular focus on the therapeutic potential and molecular mechanisms of the action of polyphenolic compounds (especially flavonoids and tannins), which have been the subject of many recently published articles. Full article

(This article belongs to the Special Issue Phytochemicals and Antioxidant, Anti-inflammatory and Cytotoxic Properties)

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