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Korpayev S, Zengin G, Ak G, Glamočlija J, Soković M, Aničić N, Gašić U, Stojković D, Agamyradov M, Cetiz MV, Agamyradova G. Integration of In Vitro and In Silico Results From Chemical and Biological Assays of Rheum turkestanicum and Calendula officinalis Flower Extracts. Food Sci Nutr 2025; 13:e4663. [PMID: 39803294 PMCID: PMC11717056 DOI: 10.1002/fsn3.4663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 11/02/2024] [Accepted: 11/28/2024] [Indexed: 01/16/2025] Open
Abstract
In this study, we conducted a thorough analysis of Rheum turkestanicum (RT) and Calendula officinalis flowers (COF) extracts with varying polarities using LC-MS chemical profiling and biological tests (antioxidant, antimicrobial, enzyme inhibition, and cytotoxic effects). The highest level of total phenolic content in the ethanol extract of RT with 75.82 mg GAE/g, followed by the infusions of RT (65.00 mg GAE/g) and COF (40.99 mg GAE/g). A total of 20 bioactive compounds were identified and quantified. The ethanol extract of COF was rich in terms of 5-O-caffeoylquinic acid (2780.56 μg/g), isorhamnetin-O-rutinoside (1653.59 μg/g), and rutin (1356.97 μg/g). However, RF extracts were rich in catechin gallate (21.66-80.01 μg/g) and 5-O-caffeoylquinic acid. Except for metal chelating ability, the ethanol extract of RT exhibited the strongest ability (DPPH: 171.5 mg TE/g; ABTS: 387.35 mg TE/g; CUPRAC: 449.80 mg TE/g; FRAP: 195.60 mg TE/g; and PBD: 1.52 mmol TE/g). In the enzyme inhibition tests, the tested ethanol extracts for both species were more active than the infusion. The highest values for tyrosinase were recorded as 72.47 mg KAE/g (in RT extracts) and 71.74 mg KAE/g (in COF extracts). Furthermore, all extracts underwent assessment for their antibacterial and antifungal properties, targeting both Gram-positive and Gram-negative bacteria, as well as clinical yeast and fungal microorganisms. In silico studies yielded valuable insights into the potential therapeutic applications of the bioactive compounds identified in COF and RT extracts. Stable interactions were observed between key compounds, such as isorhamnetin 3-O-glucoside and 3-O-caffeoylquinic acid, with crucial target proteins (AChE, BChE, and MurE). These compounds formed stable hydrogen bonds with minimal root mean square deviation (RMSD) fluctuations, particularly in the isorhamnetin 3-O-glucoside-Staphylococcus aureus MurE and 3-O-caffeoylquinic acid-MurE of S. aureus complexes. These findings further underscore the potential of these compounds as promising candidates for therapeutic development.
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Affiliation(s)
| | - Gokhan Zengin
- Department of Biology, Science FacultySelcuk UniversityKonyaTurkey
| | - Gunes Ak
- Department of Biology, Science FacultySelcuk UniversityKonyaTurkey
| | - Jasmina Glamočlija
- Department of Plant Physiology, Institute for Biological Research “Siniša Stanković” – National Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia
| | - Marina Soković
- Department of Plant Physiology, Institute for Biological Research “Siniša Stanković” – National Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia
| | - Neda Aničić
- Department of Plant Physiology, Institute for Biological Research “Siniša Stanković” – National Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia
| | - Uroš Gašić
- Department of Plant Physiology, Institute for Biological Research “Siniša Stanković” – National Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia
| | - Dejan Stojković
- Department of Plant Physiology, Institute for Biological Research “Siniša Stanković” – National Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia
| | - Mirap Agamyradov
- Saint Petersburg State Pediatric Medical UniversitySt PetersburgRussia
| | - Mehmet Veysi Cetiz
- Department of Biology, Science FacultySelcuk UniversityKonyaTurkey
- Cetiz Lab.SanlıurfaTurkey
- Department of ChemistryRecep Tayyip Erdogan UniversityRizeTurkey
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Korpayev S, Zengin G, Glamočlija J, Soković M, Aničić N, Gašić U, Stojković D, Agamuradov M, Agamyradova G. Studies on the Bioactivity (Antioxidant, Enzyme Inhibitory, Antimicrobial and Cytotoxic) and Chemical Composition of Aqueous Extracts of Some Plant Species Collected from Turkmenistan. Chem Biodivers 2025; 22:e202401493. [PMID: 39306843 DOI: 10.1002/cbdv.202401493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 09/16/2024] [Indexed: 11/09/2024]
Abstract
Alhagi persarum (AP), Alhagi persarum flowers (APF), Ephedra equisetina (EE) and Glycyrrhiza glabra root (GGR) have been utilized in Central Asian folk medicine for centuries. In the present study, antioxidant, enzyme inhibition, antimicrobial and cytotoxic effects the aqueous extracts of these plants were studied. In addition, 23 compounds were identified in the extracts using UHPLC-DAD-QqQ-MS/MS analysis. The four plant samples demonstrated promising antioxidant activities in vitro for scavenging of 2, 20-azinobis-(3-ethylbenz-thiazoline-6-sulphonate) radical (ABTS), 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH), and total reducing power. AP (DPPH: 47.39 mg TE/g; ABTS:108.58 mg TE/g; CUPRAC: 117.41 mg TE/g; FRAP: 82.22 mg TE/g) and EE (DPPH: 46.75 mg TE/g; ABTS: 110.51 mg TE/g; CUPRAC: 140.77 mg TE/g; FRAP: 91.00 mg TE/g) displayed the strongest antiradical and reduction abilities in the test system. In terms of enzyme inhibition efficacy, AP and EE showed higher bioactivity. Aqueous extracts demonstrated the most potent efficacy against eight different bacterial and fungal strains in antibacterial (MIC values: 1.5-4 mg/ml) and antifungal (MIC values: 1-8 mg/ml) testing. Contrary to other activities, these aqueous extracts did not show cytotoxic effects against HaCaT cells. All bioactivities suggested that the plants could be utilized as candidate resources in the food and pharmaceutical industries.
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Affiliation(s)
- Serdar Korpayev
- Biotechnology Institute, Ankara University, 06100, Ankara, Turkey
| | - Gökhan Zengin
- Department of Biology, Science Faculty, Selcuk University, Konya, Turkey
| | - Jasmina Glamočlija
- 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
| | - Marina Soković
- 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
| | - Neda Aničić
- 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
| | - Uroš Gašić
- 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
| | - Dejan Stojković
- 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
| | - Mirap Agamuradov
- Saint-Petersburg State Pediatric Medical University, Saint Petersburg, Russia
| | - Guljan Agamyradova
- Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia
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Messaoudi K, Benmeddour T, Flamini G. First report on the chemical composition and the free radical scavenging and antimicrobial activities of the essential oil of Ononis aurasiaca, an endemic plant of Algeria. Nat Prod Res 2024; 38:4355-4367. [PMID: 37971903 DOI: 10.1080/14786419.2023.2282113] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 07/10/2023] [Accepted: 07/31/2023] [Indexed: 11/19/2023]
Abstract
This study represents the first investigation of the chemical composition and the antioxidant and antimicrobial activities of Ononis aurasiaca Förther & Podlech, a plant species endemic to the Aures Mountains of Algeria. The essential oil of the plant aerial parts was analysed using GC-MS. The in vitro antioxidant activity was evaluated using three methods. A total of 44 compounds were identified. The major constituents were dodecanal, hexahydrofarnesylacetone, 2-tridecanone, phytol, 1-heneicosene, and n-heneicosane. The oil displayed significant activity in the β-carotene bleaching assay, moderate scavenging activity against DPPH radicals and a low ability to reduce iron ions. Antibacterial tests conducted on four strains revealed effectiveness primarily against Gram-positive strains, specifically Staphylococcus aureus ATCC 25923 and ATCC 43300, while showing limited impact on Gram-negative strains, Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922. Antifungal activity tests involving two moulds revealed a stronger inhibition against Scedosporium apiospermum compared to Aspergillus niger.
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Affiliation(s)
- Khadidja Messaoudi
- Department of Nature and Life Sciences, University of Biskra, Biskra, Algeria
- Laboratory of Genetics, Biotechnology and Valorization of Bioresources, University of Biskra, Algeria
| | - Tarek Benmeddour
- Department of Nature and Life Sciences, University of Biskra, Biskra, Algeria
- Laboratory of Genetics, Biotechnology and Valorization of Bioresources, University of Biskra, Algeria
| | - Guido Flamini
- Dipartimento di Farmacia, Università di Pisa, Pisa, Italy
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Wang D, Chen Y, Li J, Wu E, Tang T, Singla RK, Shen B, Zhang M. Natural products for the treatment of age-related macular degeneration. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 130:155522. [PMID: 38820665 DOI: 10.1016/j.phymed.2024.155522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 02/08/2024] [Accepted: 03/07/2024] [Indexed: 06/02/2024]
Abstract
BACKGROUND Age-related macular degeneration (AMD) is a chronic retinal disease that significantly influences the vision of the elderly. PURPOSE There is no effective treatment and prevention method. The pathogenic process behind AMD is complex, including oxidative stress, inflammation, and neovascularization. It has been demonstrated that several natural products can be used to manage AMD, but systematic summaries are lacking. STUDY DESIGN AND METHODS PubMed, Web of Science, and ClinicalTrials.gov were searched using the keywords "Biological Products" AND "Macular Degeneration" for studies published within the last decade until May 2023 to summarize the latest findings on the prevention and treatment of age-related macular degeneration through the herbal medicines and functional foods. RESULTS The eligible studies were screened, and the relevant information about the therapeutic action and mechanism of natural products used to treat AMD was extracted. Our findings demonstrate that natural substances, including retinol, phenols, and other natural products, prevent the development of new blood vessels and protect the retina from oxidative stress in cells and animal models. However, they have barely been examined in clinical studies. CONCLUSION Natural products could be highly prospective candidate drugs used to treat AMD, and further preclinical and clinical research is required to validate it to control the disease.
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Affiliation(s)
- Dongyue Wang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China
| | - Yi Chen
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China
| | - Jiakun Li
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China; Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, PR China
| | - Erman Wu
- Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, PR China
| | - Tong Tang
- Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, PR China
| | - Rajeev K Singla
- Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, PR China; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab-144411, India.
| | - Bairong Shen
- Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, PR China.
| | - Ming Zhang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
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Paździora W, Paśko P, Grabowska K, Galanty A. Can Isoflavone-Rich Legume Plants Be Useful in the Chemoprevention of Hormone-Dependent Cancers?-A Systematic Review. Int J Mol Sci 2024; 25:7389. [PMID: 39000493 PMCID: PMC11242776 DOI: 10.3390/ijms25137389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 07/02/2024] [Accepted: 07/03/2024] [Indexed: 07/16/2024] Open
Abstract
Plants from the Fabaceae family are widely distributed around the world, especially in Europe, Asia and North America. They are a rich source of isoflavones, compounds with estrogen-like activity, which are suspected of having a chemopreventive effect against hormone-dependent cancers. Following the PRISMA guidelines, we conducted a systematic review aimed at assessing the impact of Fabaceae plant extracts on hormone-dependent cancer cells and the content of active compounds in plant raw materials. We analyzed the results of 63 articles from in vitro and in vivo studies describing the effect of plant extracts containing isoflavones on cancer cells, along with their anti-inflammatory and antioxidant potential. In the process, we determined the research limitations and future research directions. The collected results indicate the plant species with potentially high contents of phytoestrogens and anti-inflammatory, antioxidant and cytotoxic properties. They point to the potential use of plants in the diet as a source of compounds offering cancer prevention.
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Affiliation(s)
- Wojciech Paździora
- Department of Pharmacognosy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland; (W.P.); (K.G.)
- Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, 16 Łazarza Str., 31-530 Cracow, Poland
| | - Paweł Paśko
- Department of Food Chemistry and Nutrition, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland;
| | - Karolina Grabowska
- Department of Pharmacognosy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland; (W.P.); (K.G.)
| | - Agnieszka Galanty
- Department of Pharmacognosy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland; (W.P.); (K.G.)
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Yin R, Gao J, Liu Y. Mechanisms analysis for Formononetin counteracted-Osimertinib resistance in non-small cell lung cancer cells: From the insight into the gene transcriptional level. Chem Biol Drug Des 2024; 103:e14435. [PMID: 38230781 DOI: 10.1111/cbdd.14435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 12/05/2023] [Accepted: 12/15/2023] [Indexed: 01/18/2024]
Abstract
Formononetin is one of the main isoflavone components, which has strong anti-cancer effects in non-small cell lung cancer (NSCLC). However, the potentials and the mechanisms of Formononetin to counteract the Osimertinib resistance in NSCLC are unclear. In this study, Formononetin-induced cell apoptosis, cell proliferation, and clonal formation were detected in Osimertinib-resistant NSCLC cells (H1975_OR). RNA sequencing analysis was conducted to study the gene expression profiles of Formononetin-induced H1975_OR cells. The results indicated that Formononetin could significantly induce cell apoptosis, whereas dramatically inhibited cell proliferation and clonal formation on H1975_OR cells. Furthermore, a total of 4309 differentially expressed genes (DEGs) between Formononetin-treated and nontreated H1975_OR cells were had been detected. Gene Ontology (GO) annotation enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and the Gene Set Enrichment Analysis (GSEA) showed that Formononetin affected the expression of genes involving in anatomical structure morphogenesis, anatomical structure development, and multicellular organism development via regulating inflammation- and metabolism-related signaling pathways. Taken together, our study preliminarily revealed the mechanisms of Formononetin to counteract the Osimertinib resistance in NSCLC cells from the transcriptional level and provided a potential treatment method for Osimertinib-resistant NSCLC patients.
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Affiliation(s)
- Runyang Yin
- Department of Anesthesiology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Jing Gao
- First Clinical Medical College, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Yang Liu
- Department of Clinical Laboratory, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
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Marković T, Čutović N, Carević T, Gašić U, Stojković D, Xue J, Jovanović A. Paeonia peregrina Mill Petals as a New Source of Biologically Active Compounds: Chemical Characterization and Skin Regeneration Effects of the Extracts. Int J Mol Sci 2023; 24:11764. [PMID: 37511520 PMCID: PMC10380736 DOI: 10.3390/ijms241411764] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/28/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
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).
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Affiliation(s)
- Tatjana Marković
- Institute for Medicinal Plants Research "Dr Josif Pančić", Tadeuša Košćuška 1, 11000 Belgrade, Serbia
| | - Natalija Čutović
- Institute for Medicinal Plants Research "Dr Josif Pančić", Tadeuša Košćuška 1, 11000 Belgrade, Serbia
| | - Tamara Carević
- 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
| | - Uroš Gašić
- 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
| | - Dejan Stojković
- 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
| | - Jingqi Xue
- Key Laboratory of Biology and Genetic Improvement of Horticultural Crops, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Ministry Agriculture and Rural Affairs, Beijing 100081, China
| | - Aleksandra Jovanović
- Institute for the Application of Nuclear Energy INEP, University of Belgrade, Banatska 31b, Zemun, 11080 Belgrade, Serbia
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Perović T, Petrović J, Gašić U, Kostić M, Ćirić A. Natural extracts against agricultural pathogens: A case study of Celtis australis L. Food Sci Nutr 2023; 11:3358-3364. [PMID: 37324890 PMCID: PMC10261757 DOI: 10.1002/fsn3.3325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 02/14/2023] [Accepted: 03/10/2023] [Indexed: 06/17/2023] Open
Abstract
Plant extracts and other plant products have been used as an alternative to synthetic fungicides or an additional way to reduce their use. The choice of plant extracts and their application depends on their functional characteristics, availability, cost-effectiveness, and their impact on phytopathogens, and also on the environment. Therefore, the present study aims to assess the potential of Celtis australis methanolic extracts as source of compounds with antifungal activity. Methanolic extracts prepared from leaves and unripe mesocarps of C. australis collected from different localities of Montenegro (Podgorica-PG, Donja Gorica-DG, and Bar-BR) were evaluated for their phenolic compounds' composition as well as antifungal and cytotoxic properties. Obtained results revealed that extracts contain various bioactive constituents including phenolic acids, flavonoids, and their derivatives. The predominant phenolic acid was ferulic acid, identified in leaf samples from DG (187.97 mg/100 g dw), while isoorientin was the most abundant phenolic compound found in all examined samples. Regarding antifungal potential of the tested samples, all but one (prepared from mesocarp BR) possessed higher activity than Previcur, a commercial systemic fungicide intended to control seedlings. In vitro studies on HaCaT cell line showed that the extracts had no toxic effect toward the tested cell line. These results lead to the conclusion that methanolic extracts of C. australis can become an alternative to the use of synthetic fungicides in agriculture. Those extracts represent natural biodegradable fungicides and enable more efficient control of pathogenic fungi.
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Affiliation(s)
- Tatjana Perović
- Biotechnical Faculty, Centre for Subtropical CulturesUniversity of MontenegroBarMontenegro
| | - Jovana Petrović
- Department of Plant Physiology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia
| | - Uroš Gašić
- Department of Plant Physiology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia
| | - Marina Kostić
- Department of Plant Physiology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia
| | - Ana Ćirić
- Department of Plant Physiology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia
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Extraction Optimization, Preliminary Identification, and Bioactivities in Corn Silk. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2023; 2023:5685174. [PMID: 36777625 PMCID: PMC9911244 DOI: 10.1155/2023/5685174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 10/08/2022] [Accepted: 10/11/2022] [Indexed: 02/05/2023]
Abstract
For thousands of years, corn silk has been widely used as an antidiabetic, antioxidant, and antihyperlipidemic and for other effects, but there is a lack of studies that correlate the extracts of flavonoid composition with their biological activities. Thus, the objectives of this study were to optimize the conditions for extracting flavonoids, identify flavonoids, and correlate the flavonoid composition with the biological activities in corn silk. The response surface experiments showed that the highest flavonoid content was predicted at 45.321 min, 57.349°C, 26.089 mL/g, and 71.269%, respectively. The verification experiment results under these optimized conditions showed an ultrasonic time of 45 min, an ultrasonic temperature of 57°C, a liquid-to-material ratio of 26, and an ethanol volume fraction of 70%. No significant differences (the relative error is 4.378%) were observed between the theoretical and experimental TFC values, indicating that the developed models were accurate. Under these optimum extraction conditions, 20 major compounds were identified and quantified by UPLC-LTQ/Orbitrap MS. Furthermore, these optimum ethanol extracts of corn silk are effective against Bacillus subtilis and hypoglycemic activity compared with the traditional heating reflux extraction method. Six corn silk components seem to be the main contributors to the inhibitory effect against Bacillus subtilis and hyperglycemia activities. These results are useful for the application of corn silk in the food or pharmaceutical industry.
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Rajčević N, Bukvički D, Dodoš T, Marin PD. Interactions between Natural Products-A Review. Metabolites 2022; 12:metabo12121256. [PMID: 36557296 PMCID: PMC9786035 DOI: 10.3390/metabo12121256] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 12/03/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Abstract
Plant-based natural products have been used as a source for therapeutics since the dawn of civilization. According to the World Health Organization (WHO), more than 80% of the world's population relies on traditional medicine for their primary healthcare. Numerous natural extracts, widely known in Traditional Chinese Medicine, Indian Ayurveda medicine and other practices, have led to the modern discovery and development of new drugs. Plants continuously interact with their environment, producing new compounds and ever-changing combinations of existing ones. Interestingly, some of the compounds have shown lower therapeutic activity in comparison to the extract they were isolated from. These findings suggest that the higher therapeutic activity of the source extract was due to the synergistic effect of several compounds. In other words, the total therapeutic potential of the extract cannot be explained only by the sum of its parts alone. In traditional medicine, most herbal remedies are based on a mixture of plants, and it is the interaction between different constituents that amplifies their therapeutic potential. Considering the significant influence traditional medicine has on human healthcare, knowing and studying the synergistic effect of compounds is paramount in designing smart therapeutic agents.
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Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma. Cells 2022; 11:cells11162530. [PMID: 36010607 PMCID: PMC9406959 DOI: 10.3390/cells11162530] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 08/06/2022] [Accepted: 08/09/2022] [Indexed: 11/29/2022] Open
Abstract
Glioblastoma (GBM) is the most common and highly lethal type of brain tumor, with poor survival despite advances in understanding its complexity. After current standard therapeutic treatment, including tumor resection, radiotherapy and concomitant chemotherapy with temozolomide, the median overall survival of patients with this type of tumor is less than 15 months. Thus, there is an urgent need for new insights into GBM molecular characteristics and progress in targeted therapy in order to improve clinical outcomes. The literature data revealed that a number of different signaling pathways are dysregulated in GBM. In this review, we intended to summarize and discuss current literature data and therapeutic modalities focused on targeting dysregulated signaling pathways in GBM. A better understanding of opportunities for targeting signaling pathways that influences malignant behavior of GBM cells might open the way for the development of novel GBM-targeted therapies.
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Stojkovic D, Drakulic D, Dias MI, Zengin G, Barros L, Ivanov M, Gašic U, Rajcevic N, Stevanovic M, Ferreira ICFR, Sokovic M. Phlomis fruticosa L. exerts in vitro antineurodegenerative and antioxidant activities and induces prooxidant effect in glioblastoma cell line. EXCLI JOURNAL 2022; 21:387-399. [PMID: 35368464 PMCID: PMC8971322 DOI: 10.17179/excli2021-4487] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 02/09/2022] [Indexed: 12/12/2022]
Abstract
Despite the significant advances in drug development we are witnessing the inability of health systems to combat both neurodegenerative diseases and cancers, especially glioblastoma. Hence, natural products are comprehensively studied in order to provide novel therapeutic options. This study aimed to explore anti-neurodegenerative and anti-glioblastoma potential of extract of Phlomis fruticosa L. using in vitro model systems. It was found that the methanol extract of P. fruticosa was able to efficiently reduce activities of enzymes linked to neurodegenerative disease including acetylcholinesterase, butyrylcholinesterase and tyrosinase. Furthermore, P. fruticosa extract has shown excellent antioxidant potential, as evidenced by six different methods. Analysis of cytotoxic effect of P. fruticosa extract on A172 glioblastoma cell line revealed that the concentration of the extract necessary for 50 % inhibition of A172 growth (IC50) was 710 μg/mL. The extract did not induce changes in proliferation and morphology of A172 glioblastoma cells. On the other side, production of ROS was increased in A172 cells treated with the extract. Observed cytotoxic effect of P. fruticosa extract might be based on increase in ROS generation upon treatment. Quantitative chemical analysis revealed the presence of twelve different polyphenols with the cis 3-O-caffeoylquinic acid being the most abundant. This study provided scientific evidence for further exploration of P. fruticosa as a promising natural anti-neurodegenerative therapeutic option.
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Affiliation(s)
- Dejan Stojkovic
- Department of Plant Physiology, Institute for Biological Research "Siniša Stankovic" - National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia
| | - Danijela Drakulic
- Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11042 Belgrade 152, Serbia
| | - Maria Inês Dias
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal
| | - Gokhan Zengin
- Physiology and Biochemistry Research Laboratory, Department of Biology, Science Faculty, Selcuk University, Campus, 42130, Konya, Turkey
| | - Lillian Barros
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal
| | - Marija Ivanov
- Department of Plant Physiology, Institute for Biological Research "Siniša Stankovic" - National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia
| | - Uroš Gašic
- Department of Plant Physiology, Institute for Biological Research "Siniša Stankovic" - National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia
| | - Nemanja Rajcevic
- University of Belgrade, Faculty of Biology, Studentski trg 16, 11158 Belgrade, Serbia
| | - Milena Stevanovic
- Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11042 Belgrade 152, Serbia.,University of Belgrade, Faculty of Biology, Studentski trg 16, 11158 Belgrade, Serbia.,Serbian Academy of Sciences and Arts, Kneza Mihaila 35, 11000 Belgrade, Serbia
| | - Isabel C F R Ferreira
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal
| | - Marina Sokovic
- Department of Plant Physiology, Institute for Biological Research "Siniša Stankovic" - National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia
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Đorđevski N, Stojković D, Živković J, Pljevljakušić D, Ristanović E, Nikolić B, Ćirić A. Tamjanika, a Balkan native variety of Vitis vinifera L.: Chemical characterization, antibacterial, and anti-dermatomycosis potential of seed oil. Food Sci Nutr 2022; 10:1312-1319. [PMID: 35432959 PMCID: PMC9007293 DOI: 10.1002/fsn3.2777] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 10/22/2021] [Accepted: 10/22/2021] [Indexed: 12/14/2022] Open
Abstract
This study was designed to explore functional food properties of edible seed oil obtained from Tamjanika seeds—autochthonous grape variety of Balkan Peninsula. In order to accomplish our goals, seed oil was isolated by Soxhlet apparatus and chemically characterized regarding fatty acids, carotenoids, tocopherols, and tocotrienols. Antimicrobial activity of the isolated oil was tested by microdilution method. For that purposes, six bacterial species were used, belonging to human infectious agents and food contaminants. Furthermore, the activity of the oil was investigated against clinical isolates of dermatomycetes. Our study has shown that oil of Vitis vinifera L. Tamjanika variety was an abundant source of polyunsaturated fatty acids (81.43%) with predominant linoleic acid. HPLC analysis revealed the presence of carotenoid lutein (0.15 mg/100 g). The seed oil was rich in tocotrienols (85.04 mg/100 g) predominating over tocopherols (8.37 mg/100 g). The oil possessed microbicidal activity against all the tested microbes. Bacteria were more sensitive to the effect of the oil (minimum inhibitory concentration [MIC] 7.7–15.4) when compared with oil effect on tested dermatomycetes (MIC 20–40). Our investigation has shown for the first time that grape oil could be active against wide spectrum of bacteria and clinically isolated dermatomycetes. The significance of this study lies in the fact that it pointed out the functional food properties of grape seed oil that was fully chemically characterized.
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Affiliation(s)
- Nikoleta Đorđevski
- Laboratory of Immunology Institute of Microbiology Medical Military Academy Belgrade Serbia
| | - Dejan Stojković
- Department of Plant Physiology Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia University of Belgrade Belgrade Serbia
| | - Jelena Živković
- Institute for Medicinal Plant Research "Dr Josif Pancic" Belgrade Serbia
| | | | - Elizabeta Ristanović
- Laboratory of Immunology Institute of Microbiology Medical Military Academy Belgrade Serbia
| | - Biljana Nikolić
- Faculty of Biology Belgrade University of Belgrade Belgrade Serbia
| | - Ana Ćirić
- Department of Plant Physiology Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia University of Belgrade Belgrade Serbia
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14
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Besrour N, Oludemi T, Mandim F, Pereira C, Dias MI, Soković M, Stojković D, Ferreira O, Ferreira ICFR, Barros L. Valorization of Juglans regia Leaves as Cosmeceutical Ingredients: Bioactivity Evaluation and Final Formulation Development. Antioxidants (Basel) 2022; 11:antiox11040677. [PMID: 35453361 PMCID: PMC9031312 DOI: 10.3390/antiox11040677] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 03/29/2022] [Accepted: 03/29/2022] [Indexed: 02/06/2023] Open
Abstract
The cosmetic industry is constantly searching for bioactive ingredients, namely, those obtained from natural sources with environmentally friendly connotations and less toxic effects. A previous study of our research group optimized the extraction of phenolic compounds from Juglans regia by heat-assisted extraction. Due to its richness in different phenolic compounds, the present work aimed to develop a formulation containing J. regia leaf extract. The extract’s antioxidant, anti-tyrosinase, antimicrobial, anti-inflammatory, wound healing, cytotoxicity, and photostability properties were evaluated. The extract was then incorporated into an O/W base cream, followed by characterization of the final formulation in terms of its antioxidant properties, phenolic composition, and stability over time and at different storage conditions. The most abundant compounds in the hydroethanolic extract were 3-O-caffeoylquinic acid (18.30 ± 0.04 mg/g), quercetin-O-pentoside (9.64 ± 0.06 mg/g), and quercetin 3-O-glucoside (6.70 ± 0.19 mg/g). Besides those, the extract presented antioxidant, anti-inflammatory, wound closure, and antibacterial effects against several skin pathogens. In addition, HaCaT cell viability was maintained up to 98% at 400 µg/mL. Within Proteus vulgaris-infected HaCaT cells, the extract also presented an over 40% bacterial mortality rate at its nontoxic concentration (200 µg/mL). After incorporating the extract, the obtained formulation presented a good physicochemical profile over time and at different storage conditions while also maintaining its antioxidant effect; as such, it can be considered stable for topical application. Future work to evaluate its performance in terms of skin permeation and detailed toxicological studies with a focus on regulatory requirements, involving skin irritation, eye irritation, genotoxicity, photo-irritation, and dermal absorption, should be conducted, as the prepared formulation demonstrated relevant properties that deserve to be further explored.
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Affiliation(s)
- Nermine Besrour
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (N.B.); (T.O.); (F.M.); (C.P.); (M.I.D.); (I.C.F.R.F.)
| | - Taofiq Oludemi
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (N.B.); (T.O.); (F.M.); (C.P.); (M.I.D.); (I.C.F.R.F.)
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Science, Univeridade de Vigo, 36310 Ourense, Spain
| | - Filipa Mandim
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (N.B.); (T.O.); (F.M.); (C.P.); (M.I.D.); (I.C.F.R.F.)
| | - Carla Pereira
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (N.B.); (T.O.); (F.M.); (C.P.); (M.I.D.); (I.C.F.R.F.)
| | - Maria Inês Dias
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (N.B.); (T.O.); (F.M.); (C.P.); (M.I.D.); (I.C.F.R.F.)
| | - Marina Soković
- 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; (M.S.); (D.S.)
| | - Dejan Stojković
- 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; (M.S.); (D.S.)
| | - Olga Ferreira
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (N.B.); (T.O.); (F.M.); (C.P.); (M.I.D.); (I.C.F.R.F.)
- Correspondence: (O.F.); (L.B.); Tel.: +351-273-303-285 (L.B.); Fax: +351-273-325-405 (L.B.)
| | - Isabel C. F. R. Ferreira
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (N.B.); (T.O.); (F.M.); (C.P.); (M.I.D.); (I.C.F.R.F.)
| | - Lillian Barros
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (N.B.); (T.O.); (F.M.); (C.P.); (M.I.D.); (I.C.F.R.F.)
- Correspondence: (O.F.); (L.B.); Tel.: +351-273-303-285 (L.B.); Fax: +351-273-325-405 (L.B.)
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Polyphenols as Inhibitors of Antibiotic Resistant Bacteria-Mechanisms Underlying Rutin Interference with Bacterial Virulence. Pharmaceuticals (Basel) 2022; 15:ph15030385. [PMID: 35337182 PMCID: PMC8952364 DOI: 10.3390/ph15030385] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 03/18/2022] [Accepted: 03/19/2022] [Indexed: 02/01/2023] Open
Abstract
The rising incidence of antibiotic resistant microorganisms urges novel antimicrobials development with polyphenols as appealing potential therapeutics. We aimed to reveal the most promising polyphenols among hesperetin, hesperidin, naringenin, naringin, taxifolin, rutin, isoquercitrin, morin, chlorogenic acid, ferulic acid, p-coumaric acid, and gallic acid based on antimicrobial capacity, antibiofilm potential, and lack of cytotoxicity towards HaCaT, and to further test its antivirulence mechanisms. Although the majority of studied polyphenols were able to inhibit bacterial growth and biofilm formation, the most promising activities were observed for rutin. Further investigation proved rutin’s ability to prevent/eradicate Pseudomonas aeruginosa and MRSA urinary catheter biofilms. Besides reduction of biofilm biomass, rutin antibiofilm mechanisms included reduction of cell viability, exopolysaccharide, and extracellular DNA levels. Moderate reduction of bacterial adhesion to human keratinocytes upon treatment was observed. Rutin antivirulence mechanisms included an impact on P. aeruginosa protease, pyocyanin, rhamnolipid, and elastase production and the downregulation of the lasI, lasR, rhlI, rhlR, pqsA and mvfR genes. Rutin also interfered with membrane permeability. Polyphenols could repress antibiotic resistant bacteria. Rutin has shown wide antimicrobial and antibiofilm capacity employing a range of mechanisms that might be used for the development of novel antimicrobials.
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17
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Stevanovic M, Kovacevic-Grujicic N, Mojsin M, Milivojevic M, Drakulic D. SOX transcription factors and glioma stem cells: Choosing between stemness and differentiation. World J Stem Cells 2021; 13:1417-1445. [PMID: 34786152 PMCID: PMC8567447 DOI: 10.4252/wjsc.v13.i10.1417] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 07/15/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Glioblastoma (GBM) is the most common, most aggressive and deadliest brain tumor. Recently, remarkable progress has been made towards understanding the cellular and molecular biology of gliomas. GBM tumor initiation, progression and relapse as well as resistance to treatments are associated with glioma stem cells (GSCs). GSCs exhibit a high proliferation rate and self-renewal capacity and the ability to differentiate into diverse cell types, generating a range of distinct cell types within the tumor, leading to cellular heterogeneity. GBM tumors may contain different subsets of GSCs, and some of them may adopt a quiescent state that protects them against chemotherapy and radiotherapy. GSCs enriched in recurrent gliomas acquire more aggressive and therapy-resistant properties, making them more malignant, able to rapidly spread. The impact of SOX transcription factors (TFs) on brain tumors has been extensively studied in the last decade. Almost all SOX genes are expressed in GBM, and their expression levels are associated with patient prognosis and survival. Numerous SOX TFs are involved in the maintenance of the stemness of GSCs or play a role in the initiation of GSC differentiation. The fine-tuning of SOX gene expression levels controls the balance between cell stemness and differentiation. Therefore, innovative therapies targeting SOX TFs are emerging as promising tools for combatting GBM. Combatting GBM has been a demanding and challenging goal for decades. The current therapeutic strategies have not yet provided a cure for GBM and have only resulted in a slight improvement in patient survival. Novel approaches will require the fine adjustment of multimodal therapeutic strategies that simultaneously target numerous hallmarks of cancer cells to win the battle against GBM.
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Affiliation(s)
- Milena Stevanovic
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11042, Serbia
- Chair Biochemistry and Molecular Biology, Faculty of Biology, University of Belgrade, Belgrade 11158, Serbia
- Department of Chemical and Biological Sciences, Serbian Academy of Sciences and Arts, Belgrade 11000, Serbia.
| | - Natasa Kovacevic-Grujicic
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11042, Serbia
| | - Marija Mojsin
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11042, Serbia
| | - Milena Milivojevic
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11042, Serbia
| | - Danijela Drakulic
- Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11042, Serbia
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Zengin G, Stojković D, Mahomoodally MF, Jugreet BS, Paksoy MY, Ivanov M, Gašić U, Gallo M, Montesano D. Comprehensive Biological and Chemical Evaluation of Two Seseli Species ( S. gummiferum and S. transcaucasicum). Antioxidants (Basel) 2021; 10:1510. [PMID: 34679647 PMCID: PMC8532678 DOI: 10.3390/antiox10101510] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 09/13/2021] [Accepted: 09/20/2021] [Indexed: 12/11/2022] Open
Abstract
Seseli L. is one of the largest genera of the Apiaceae family widely known for their traditional uses as herbal remedies. In the present study, the methanolic and water extracts of two Seseli species, S. gummiferum and S. transcaucasicum were evaluated for their bioactive contents and biological activities. The total phenolic and flavonoid contents in the extracts ranged from 19.09 to 24.33 mg GAE/g and from 0.45 to10.09 mg RE/g, respectively. Moreover, while narcissin was detected as the most abundant component in the methanolic extract of S. transcaucasicum (261.40 µg/g), chlorogenic acid was identified as the major component in all the other extracts, although a high amount was also present in the methanolic S. transcaucasicum extract (107.48-243.12 µg/g). The total antioxidant capacity was also determined by the phosphomolybdenum assay (0.66-1.18 mM TE/g). Other antioxidant assays such as the radical scavenging assays (DPPH: 5.51-11.45 mg TE/g; ABTS: 43.46-51.91 mg TE/g), reducing assays (CUPRAC: 41.67-53.20 mg TE/g; FRAP: 31.26-34.14 mg TE/g), as well as the metal chelating activity assay (14.38-38.57 mg EDTAE/g) were conducted. All the extracts showed inhibitory potential against the enzyme's amylase (0.12-0.78 mM ACAE/g), acetyl- and butyryl-cholinesterase (0.15-9.71 mg GALAE/g), while only the methanolic extracts acted as inhibitors of tyrosinase (107.15 and 109.37 mg KAE/g) and only the water extract of S. gummiferum displayed anti-glucosidase activity (0.13 mM ACAE/g). Interestingly, the methanolic extracts of both Seseli species showed lower cytotoxicity towards HaCaT cells (IC50: >500 µg/mL), compared to the water extracts (IC50: 267.8 and 321.41 µg/mL). Besides, only the methanolic extracts showed a slight wound healing effect (28.21 and 31.23%). All extracts showed antibacterial action against Staphylococcus lugdunensis (minimum inhibitory and bactericidal concentrations: 0.025-2 mg/mL). S. gummiferum methanolic extract, which exhibited the highest antibacterial potency was found to inhibit adhesion and invasion of S. lugdunensis to HaCaT cells as well. Taken together, this study demonstrated the two Seseli species to harbour interesting bioactive components, in particular polyphenolics and to exhibit several biological properties that could be further investigated for their potential exploitation as healing agents as supported by various traditional medicinal uses.
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Affiliation(s)
- Gokhan Zengin
- Department of Biology, Science Faculty, Selcuk University, 42130 Konya, Turkey
| | - Dejan Stojković
- 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; (M.I.); (U.G.)
| | - Mohamad Fawzi Mahomoodally
- Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Réduit 80837, Mauritius; (M.F.M.); (B.S.J.)
| | - Bibi Sharmeen Jugreet
- Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Réduit 80837, Mauritius; (M.F.M.); (B.S.J.)
| | - Mehmet Yavuz Paksoy
- Department of Medical Services and Techniques, Medical Documentation and Secretaryship Programme, Tunceli Vocational School, Munzur University, 62000 Tunceli, Turkey;
| | - Marija Ivanov
- 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; (M.I.); (U.G.)
| | - Uroš Gašić
- 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; (M.I.); (U.G.)
| | - Monica Gallo
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy;
| | - Domenico Montesano
- Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy
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Nanovesicles Loaded with Origanum onites and Satureja thymbra Essential Oils and Their Activity against Food-Borne Pathogens and Spoilage Microorganisms. Molecules 2021; 26:molecules26082124. [PMID: 33917147 PMCID: PMC8067826 DOI: 10.3390/molecules26082124] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 03/30/2021] [Accepted: 04/03/2021] [Indexed: 12/21/2022] Open
Abstract
Food poisoning is a common cause of illness and death in developing countries. Essential oils (EOs) could be effective and safe natural preservatives to prevent and control bacterial contamination of foods. However, their high sensitivity and strong flavor limit their application and biological effectiveness. The aim of this study was firstly the chemical analysis and the antimicrobial evaluation of the EOs of Origanum onites L. and Satureja thymbra L. obtained from Symi island (Greece), and, secondly, the formulation of propylene glycol-nanovesicles loaded with these EOs to improve their antimicrobial properties. The EOs were analyzed by GC-MS and their chemical contents are presented herein. Different nanovesicles were formulated with small average sizes, high homogeneity, and optimal ζ-potential. Microscopic observation confirmed their small and spherical shape. Antibacterial and antifungal activities of the formulated EOs were evaluated against food-borne pathogens and spoilage microorganisms compared to pure EOs. Propylene glycol-nanovesicles loaded with O. onites EO were found to be the most active formulation against all tested strains. Additionally, in vitro studies on the HaCaT cell line showed that nanovesicles encapsulated with EOs had no toxic effect. The present study revealed that both EOs can be used as alternative sanitizers and preservatives in the food industry, and that their formulation in nanovesicles can provide a suitable approach as food-grade delivery system.
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Dall'Acqua S, Ak G, Sinan KI, Elbasan F, Ferrarese I, Sut S, Yıldıztugay E, Peron G, Schievano E, Nancy Picot-Allain MC, Mahomoodally MF, Zengin G. Hypericum triquetrifolium and H. neurocalycinum as Sources of Antioxidants and Multi-Target Bioactive Compounds: A Comprehensive Characterization Combining In Vitro Bioassays and Integrated NMR and LC-MS Characterization by Using a Multivariate Approach. Front Pharmacol 2021; 12:660735. [PMID: 33841167 PMCID: PMC8033251 DOI: 10.3389/fphar.2021.660735] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 02/11/2021] [Indexed: 12/19/2022] Open
Abstract
Hypericum triquetrifolium and H. neurocalycinum were evaluated for their phytochemical content and in vitro bioactivity. NMR analyses were performed on the methanol extract of the aerial parts of H. triquetrifolium to establish the main classes of phytoconstituents. Then, LC-DAD-MSn analyses were performed in order to compare the composition of aerial parts and roots extracts of both Hypericum species, obtained using either methanol or water as solvents. Results, processed using multivariate data analysis, showed a significantly higher phenolic content of methanol extracts compared to water extracts, while minor qualitative differences were observed between the two. Distinctive flavonoid and PAC patterns were observed for H. triquetrifolium and H. neurocalycinum, and specific compounds were exclusively detected in one or the other species. Specifically, the phloroglucinols 7-epiclusianone, hyperfirin and hyperforin were present only in H. neurocalycinum, while hyperforin was detected only in H. triquetrifolium. Extracts were assayed using different in vitro tests to evaluate their antioxidant properties and their inhibitory activity against several enzymes, showing significant antioxidant and metal chelating activities. Furthermore, inhibitory properties against acetylcholinesterase, butyrylcholinesterase and tyrosinase were observed. Multivariate approaches were used to correlate biological data with the phytochemical composition of the different extracts. The results, showing positive correlations between specific chemical constituents and the measured bioactivities, represent preliminary data that could guide future studies aimed at isolating bioactive constituents from H. neurocalycinum and H. triquetrifolium for further pharmacological evaluations.
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Affiliation(s)
- Stefano Dall'Acqua
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Gunes Ak
- Department of Biology, Science Faculty, Selcuk University, Konya, Turkey
| | | | - Fevzi Elbasan
- Department of Biotechnology, Science Faculty, Selcuk University, Konya, Turkey
| | - Irene Ferrarese
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Stefania Sut
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Evren Yıldıztugay
- Department of Biotechnology, Science Faculty, Selcuk University, Konya, Turkey
| | - Gregorio Peron
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | | | | | - Mohamad Fawzi Mahomoodally
- Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Mauritius, Mauritius
| | - Gokhan Zengin
- Department of Biology, Science Faculty, Selcuk University, Konya, Turkey
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Ma B, Lou T, Wang T, Li R, Liu J, Yu S, Pei H, Tian S, Li Y, Guo Y, Wang Z, Lin Z, Wang Z, Wang J, Gao Y. Development of a UHPLC-MS/MS-based data-mining method for rapid profiling and characterization of magnolol metabolites in rat urine and plasma. ARAB J CHEM 2021. [DOI: 10.1016/j.arabjc.2020.102954] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Extract of Herba Anthrisci cerefolii: Chemical Profiling and Insights into Its Anti-Glioblastoma and Antimicrobial Mechanism of Actions. Pharmaceuticals (Basel) 2021; 14:ph14010055. [PMID: 33445425 PMCID: PMC7827728 DOI: 10.3390/ph14010055] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 12/29/2020] [Accepted: 12/29/2020] [Indexed: 12/12/2022] Open
Abstract
Anthriscus cerefolium (L.) Hoffm. is a plant traditionally used around the globe since antiquity. Although widely used in many traditional medicines in different cultures, from the scientific point of view it is poorly investigated. Glioblastoma, a tumor type with poor prognosis, is the most common and lethal brain tumor in adults. Current therapeutic strategies for glioblastoma include surgery, radiation and chemotherapy. On the other hand, it has been revealed that patients with cancers are highly susceptible to microbial infections due to the invasive nature of cancer treatment approaches. This study was designed to investigate the chemical profile of herba Anthriscii cerefoli methanolic extract by applying UHPLC-LTQ OrbiTrap MS4 analysis and to analyze its anti-glioblastoma and antimicrobial activities. This study revealed that methanolic extract of herba Anthrisc cerefolii contained phenolic acids and flavonoids, with 32 compounds being identified. Anti-glioblastoma activity was investigated in vitro using A172 glioblastoma cell line. The cytotoxic effects of the extract on A172 cells were compared to the same effect on primary human gingival fibroblast (HGF-1) cells. Decreased rate of proliferation and changes in cell morphology were detected upon treatment of A172 cells with the extract. The antimicrobial activity of extract was tested against Staphylococcus aureus and Candida species. The extract was active against the tested bacterium and yeasts, inhibiting free floating cells and microbial biofilms. This study is the first one to provide a detailed description of the chemical profile of A. cerefolium extract dealing with scientific insights into its anti-glioblastoma and antimicrobial activities.
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Lv SS, Fu Y, Chen J, Jiao Y, Chen SQ. Six phenanthrenes from the roots of Cymbidium faberi Rolfe. and their biological activities. Nat Prod Res 2020; 36:1170-1181. [PMID: 33342306 DOI: 10.1080/14786419.2020.1862836] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
A new phenanthrene compound, 7-(4-hydroxybenzyl)-8-methoxy-9,10- dihydrophenanthrene-2,5-diol (HMD), along with five known compounds (Coelonin, DD, Shancidin, HDP and MDD) were isolated from the roots of Cymbidium faberi Rolfe. (CFR). Their structures were identified using various spectroscopic methods. These compounds were reported for the first time in the genus. All isolated compounds were tested by radical-scavenging ability against 1,1-diphenyl-2-picryl-hydrazyl (DPPH), cytotoxic activity against three human cancer cell lines and inflammatory activity. Among them, Shancidin exhibited the stronger DPPH-scavenging activity (IC50=6.67 ± 0.84 μΜ) and cytotoxic activity against three tumour cell lines. Except for HDP, all compounds dose-dependently suppressed production of NO, TNF-α, IL-6 in LPS induced mouse primary peritoneal macrophage and showed anti-inflammatory activity. Moreover, 18 compounds were identified by UHPLC-LTQ-Orbitrap-MS combined with MS database, which provides a basis for further research.
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Affiliation(s)
- Shuang-Shuang Lv
- School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Yu Fu
- School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Jun Chen
- School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Yuan Jiao
- School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Sui-Qing Chen
- School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, China.,Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Henan University of Chinese Medicine, Zhengzhou, Henan, China
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Gampe N, Szakács Z, Darcsi A, Boldizsár I, Szőke É, Kuzovkina I, Kursinszki L, Béni S. Qualitative and Quantitative Phytochemical Analysis of Ononis Hairy Root Cultures. FRONTIERS IN PLANT SCIENCE 2020; 11:622585. [PMID: 33584762 PMCID: PMC7874045 DOI: 10.3389/fpls.2020.622585] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 11/30/2020] [Indexed: 05/11/2023]
Abstract
Hairy root cultures are genetically and biochemically stable, and they regularly possess the same or better biosynthetic capabilities for specialized (secondary) metabolite production compared to the intact plant. Ononis species are well-known herbal remedies in ethnopharmacology and rich sources of isoflavonoids. Besides isoflavones, less prevalent isoflavones and pterocarpans with valuable biological effects can be found in Ononis species as well. As these plants are only collected but not cultivated, biotechnological methods could play a role in the larger-scale extraction of Ononis isoflavonoids. Regarding this information, we aimed to establish Ononis spinosa and Ononis arvensis hairy root cultures (HRCs) and analyze the isoflavonoid profile of hairy root cultures qualitatively and quantitatively, in order to define their capacity to produce biologically valuable isoflavonoids. During the qualitative description, beside isoflavonoids, two new phenolic lactones, namely, bulatlactone 2″-O-β-D-glucoside and ononilactone, were isolated, and their structures were characterized for the first time. Altogether, 29 compounds were identified by the means of UPLC-Orbitrap-MS/MS. Based on UHPLC-UV-DAD measurements, the isoflavonoid spectrum of the Ononis HRCs differed markedly from wild-grown samples, as they produce a limited range of the scaffolds. The most abundant compounds in the HRCs were medicarpin glucoside and sativanone glucoside. The overall isoflavonoid production of the cultures was comparable to wild-grown O. arvensis and approximately twice as high as in wild-grown O. spinosa samples. As the overall content of wild-grown samples include more isoflavonoid derivatives, the HRCs contain structurally less divergent isoflavonoids but in higher quantity.
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Affiliation(s)
- Nóra Gampe
- Department of Pharmacognosy, Semmelweis University, Budapest, Hungary
| | - Zoltán Szakács
- Spectroscopic Research Department, Gedeon Richter Plc., Budapest, Hungary
| | - András Darcsi
- Department of Pharmacognosy, Semmelweis University, Budapest, Hungary
| | - Imre Boldizsár
- Natural Bioactive Compounds Group, Institutional Excellence Program, Department of Plant Anatomy, Eötvös Loránd University, Budapest, Hungary
| | - Éva Szőke
- Department of Pharmacognosy, Semmelweis University, Budapest, Hungary
| | - Inna Kuzovkina
- Timiryazev Institute of Plant Physiology, Russian Academy of Sciences, Moscow, Russia
| | - László Kursinszki
- Department of Pharmacognosy, Semmelweis University, Budapest, Hungary
| | - Szabolcs Béni
- Department of Pharmacognosy, Semmelweis University, Budapest, Hungary
- *Correspondence: Szabolcs Béni, ;
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