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Ginovyan M, Tadevosyan S, Shirvanyan A, Babayan A, Kusznierewicz B, Koss-Mikołajczyk I, Mróz M, Bartoszek A, Sahakyan N. The potential of blackcurrant, fig, and grape leaf extracts in the development of new preparations for overcoming antibiotic resistance and enhancing the efficacy of chemotherapeutic agents. BMC Complement Med Ther 2025; 25:148. [PMID: 40269785 DOI: 10.1186/s12906-025-04859-1] [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: 04/25/2024] [Accepted: 03/14/2025] [Indexed: 04/25/2025] Open
Abstract
The presented study aimed to assess the efficacy of crude leaf hydroethanolic extracts from blackcurrant, fig, and grape leaves in reversing antibiotic resistance and enhancing chemotherapeutic efficacy. The viability tests were employed to assess the resistance-modifying properties of the extracts both in antibiotic-resistant bacterial cells and cancer cell-lines. To elucidate the potential mechanisms of the antibiotic modulatory activity of test extracts, the changes in H+-fluxes across the cell membrane and their impact on the H+-translocating F0F1-ATPase activity in antibiotic-resistant Escherichia coli explored. Qualitative metabolomic characterization of the extracts was performed using LC-Q-Orbitrap HRMS, and quantitative analysis was carried out with UHPLC-PDA. Experiments on doxorubicin-resistant and susceptible HT-29 cells revealed that all three extracts reversed antibiotic resistance in HT-29R cells, making them susceptible to doxorubicin in a dose-dependent manner. Notably, blackcurrant, and fig significantly reduced the minimum inhibitory concentrations of ampicillin and kanamycin against resistant E. coli strains. Our results indicated that all plant extracts enhanced H+-fluxes in the investigated bacterial strain and promoted ATPase activity, suggesting a potential role in altering bacterial membrane integrity. LC-Q-Orbitrap HRMS analysis identified more than 100 major peaks, with flavonoids and phenolics being the dominant constituents. The study underscores the potential of the selected plant extracts in developing of new agents to overcome antibiotic resistance and enhance the efficacy of chemotherapeutic agents. Importantly, although these plant leaves are often considered as bio-waste, they can be used as valuable sources of bioactive compounds. This underlines the importance of re-evaluating agricultural by-products for their potential in pharmacological applications, fostering a sustainable approach in drug development.
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Affiliation(s)
- Mikayel Ginovyan
- Department of Biochemistry, Microbiology and Biotechnology, Biology Faculty, Yerevan State University, 1 Alex Manoogian St, Yerevan, 0025, Armenia
- Research Institute of Biology, Yerevan State University, 1 Alex Manoogian St, Yerevan, 0025, Armenia
| | - Silvard Tadevosyan
- Department of Biochemistry, Microbiology and Biotechnology, Biology Faculty, Yerevan State University, 1 Alex Manoogian St, Yerevan, 0025, Armenia
| | - Anahit Shirvanyan
- Department of Biochemistry, Microbiology and Biotechnology, Biology Faculty, Yerevan State University, 1 Alex Manoogian St, Yerevan, 0025, Armenia
- Research Institute of Biology, Yerevan State University, 1 Alex Manoogian St, Yerevan, 0025, Armenia
| | - Anush Babayan
- Department of Biochemistry, Microbiology and Biotechnology, Biology Faculty, Yerevan State University, 1 Alex Manoogian St, Yerevan, 0025, Armenia
| | - Barbara Kusznierewicz
- Department of Food Chemistry, Technology and Biotechnology, Faculty of Chemistry, GdańSk University of Technology, Narutowicza 11/12, Gdańsk, 80-233, Poland
| | - Izabela Koss-Mikołajczyk
- Department of Food Chemistry, Technology and Biotechnology, Faculty of Chemistry, GdańSk University of Technology, Narutowicza 11/12, Gdańsk, 80-233, Poland
| | - Marika Mróz
- Department of Food Chemistry, Technology and Biotechnology, Faculty of Chemistry, GdańSk University of Technology, Narutowicza 11/12, Gdańsk, 80-233, Poland
| | - Agnieszka Bartoszek
- Department of Food Chemistry, Technology and Biotechnology, Faculty of Chemistry, GdańSk University of Technology, Narutowicza 11/12, Gdańsk, 80-233, Poland
| | - Naira Sahakyan
- Department of Biochemistry, Microbiology and Biotechnology, Biology Faculty, Yerevan State University, 1 Alex Manoogian St, Yerevan, 0025, Armenia.
- Research Institute of Biology, Yerevan State University, 1 Alex Manoogian St, Yerevan, 0025, Armenia.
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Siddiqui MT, Olceroglu B, Gumus ZP, Senisik AM, Barlas FB. Enhancing Radiotherapy Tolerance With Papaya Seed-Derived Nanoemulsions. Food Sci Nutr 2025; 13:e70145. [PMID: 40191523 PMCID: PMC11971051 DOI: 10.1002/fsn3.70145] [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: 01/20/2025] [Revised: 03/14/2025] [Accepted: 03/22/2025] [Indexed: 04/09/2025] Open
Abstract
Flavonoid-rich plant materials have gained attention for their potential to reduce radiotherapy side effects. Carica papaya (CP) seeds, known for high flavonoid content, hold promise for therapeutic applications. This study explored the extraction and evaluation of two oils-sunflower oil-based papaya oil (SPO) and pure papaya oil (PPO)-and their nano emulsions (SPOE and PPOE), derived from CP seeds, for radioprotective effects. Chemical analysis using QTOF-MS revealed antioxidants and phytochemicals in the oils and emulsions. Size analysis and zeta potential measurements using dynamic light scattering (DLS) showed particle sizes of 140 ± 26.06 nm for PPOE and 293.7 ± 49.42 nm for SPOE. Post-radiation, both SPOE and PPOE significantly enhanced cell viability, with values of 72.24 ± 3.92 (p ≤ 0.001) and 75.85 ± 2.62 (p ≤ 0.001), respectively. These nanoemulsions show potential as topical agents for reducing radiation-induced tissue damage in radiotherapy. Despite the promising in vitro findings, further in vivo studies are needed to confirm the clinical relevance of these nanoemulsions. Additionally, their incorporation into sunscreen formulations could provide further protection against radiation-induced skin damage, broadening their potential applications.
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Affiliation(s)
| | - Bilge Olceroglu
- Institute of Nanotechnology and BiotechnologyIstanbul Univeristy‐CerrahpasaIstanbulTurkey
- Department of BiotechnologyInstitute of Health Sciences, University of Health Sciences TurkeyIstanbulTurkey
| | - Zinar Pinar Gumus
- Central Research Test and Analysis Laboratory Application and Research CenterEge UniversityIzmirTurkey
| | | | - Firat Baris Barlas
- Institute of Nanotechnology and BiotechnologyIstanbul Univeristy‐CerrahpasaIstanbulTurkey
- Clinical Research Excellence Application and Research CenterIstanbul Univeristy‐CerrahpasaIstanbulTurkey
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Hayati EK, Sabarudin A, Aulanni'am, Rozi F, Septaningsih DA, Rafi M. Liquid Chromatography-High-Resolution Mass Spectroscopy-Based Metabolomics for Identification Cytotoxic Compounds From Acalypha Indica L. on MCF-7 Breast Cancer Cells as Potential Anticancer Agents. Chem Biodivers 2025:e202402187. [PMID: 39903842 DOI: 10.1002/cbdv.202402187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 01/07/2025] [Accepted: 01/09/2025] [Indexed: 02/06/2025]
Abstract
Acalypha indica is a weed used in traditional cancer treatments. In this study, we present the first attempt to use a metabolomic approach to identify cytotoxic compounds from A. indica extract with potential anticancer properties. The leaves of A. indica were extracted using ethanol, ethyl acetate, chloroform, and n-hexane. The cytotoxic activity against MCF-7 cells was evaluated, revealing 50% inhibition concentration (IC50) values ranging from 51.88 ± 7.80 to 226.86 ± 13.27 µg/mL. Metabolite profiling using liquid chromatography-high-resolution mass spectroscopy identified 27 metabolites and principal component analysis successfully differentiated the extracts, indicating variability in the compounds extracted using each solvent. To identify the cytotoxic compounds, orthogonal partial least-squares discriminant analysis was used to correlate metabolite profiles with IC50 values from the cytotoxic assay. From the results obtained, we successfully predicted six compounds contributing to the anticancer activity of A. indica, namely hernanol, 13(S)-HpOTrE, (±)9-HpODE, (+)-catechin, traumatic acid, and one compound as assumed to be theobromine. In silico analysis predicted that (+)-catechin and hernanol bind to the alpha-estrogen receptor with an affinity similar to that of doxorubicin.
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Affiliation(s)
- Elok Kamilah Hayati
- Department of Chemistry, Faculty of Mathematics and Natural Sciences, Brawijaya University, Jl. Veteran, Malang, Indonesia
- Department of Chemistry, Faculty of Science and Technology, Universitas Islam Negeri Maulana Malik Ibrahim Malang, Jl. Gajayana No. 50, Malang, Indonesia
| | - Akhmad Sabarudin
- Department of Chemistry, Faculty of Mathematics and Natural Sciences, Brawijaya University, Jl. Veteran, Malang, Indonesia
| | - Aulanni'am
- Department of Chemistry, Faculty of Mathematics and Natural Sciences, Brawijaya University, Jl. Veteran, Malang, Indonesia
| | - Fachrur Rozi
- Department of Mathematics, Faculty of Science and Technology, Universitas Islam Negeri Maulana Malik Ibrahim Malang, Jl. Gajayana No. 50, Malang, Indonesia
| | | | - Mohamad Rafi
- Department of Chemistry, Faculty of Mathematics and Natural Sciences, IPB University, Jl. Tanjung IPB Dramaga Campus, Bogor, Indonesia
- Tropical Biopharmaca Research Center, International Research Institute of Food, Nutrition, and Health, IPB Taman Kencana Campus, Jl Taman Kencana No. 3, Bogor, Indonesia
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Chen KD, Wang KL, Chen C, Zhu YJ, Tang WW, Wang YJ, Chen ZP, He LH, Chen YG, Zhang W. Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway. World J Gastroenterol 2024; 30:2709-2725. [PMID: 38855154 PMCID: PMC11154682 DOI: 10.3748/wjg.v30.i20.2709] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 04/18/2024] [Accepted: 05/07/2024] [Indexed: 05/27/2024] Open
Abstract
BACKGROUND Constipation, a highly prevalent functional gastrointestinal disorder, induces a significant burden on the quality of patients' life and is associated with substantial healthcare expenditures. Therefore, identifying efficient therapeutic modalities for constipation is of paramount importance. Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms. Consequently, we postulate that hydrogen therapy, an emerging and promising intervention, can serve as a safe and efficacious treatment for constipation. AIM To determine whether hydrogen-rich water (HRW) alleviates constipation and its potential mechanism. METHODS Constipation models were established by orally loperamide to Sprague-Dawley rats. Rats freely consumed HRW, and were recorded their 24 h total stool weight, fecal water content, and charcoal propulsion rate. Fecal samples were subjected to 16S rDNA gene sequencing. Serum non-targeted metabolomic analysis, malondialdehyde, and superoxide dismutase levels were determined. Colonic tissues were stained with hematoxylin and eosin, Alcian blue-periodic acid-Schiff, reactive oxygen species (ROS) immunofluorescence, and immunohistochemistry for cell growth factor receptor kit (c-kit), PGP 9.5, sirtuin1 (SIRT1), nuclear factor-erythroid-2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1, Nrf2 and HO-1. A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor, EX527, into constipated rats. NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression. RESULTS HRW alleviated constipation symptoms by improving the total amount of stool over 24 h, fecal water content, charcoal propulsion rate, thickness of the intestinal mucus layer, c-kit expression, and the number of intestinal neurons. HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism. HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway. This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats. The serum metabolites, β-leucine (β-Leu) and traumatic acid, were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1. CONCLUSION HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway, modulating gut microbiota and serum metabolites. β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.
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Affiliation(s)
- Kai-Di Chen
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Kui-Ling Wang
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Chen Chen
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Yi-Jia Zhu
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Wen-Wen Tang
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Yu-Ji Wang
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Ze-Peng Chen
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Lin-Hai He
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Yu-Gen Chen
- Department of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- Jiangsu Province Key Laboratory of Tumor Systems Biology and Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- Jiangsu Collaborative Innovation Center of Chinese Medicine in Prevention and Treatment of Tumor, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Wei Zhang
- Jiangsu Province Key Laboratory of Tumor Systems Biology and Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
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Gao J, Zhang Z, Dong X, Zhao J, Peng Z, Zhang L, Xu Z, Xu L, Wang X, Guo X. Traumatic acid inhibits ACSL4 associated lipid accumulation in adipocytes to attenuate high-fat diet-induced obesity. FASEB J 2023; 37:e23278. [PMID: 37902573 DOI: 10.1096/fj.202301166r] [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: 06/11/2023] [Revised: 09/25/2023] [Accepted: 10/13/2023] [Indexed: 10/31/2023]
Abstract
Obesity is a major health concern that lacks effective intervention strategies. Traumatic acid (TA) is a potent wound-healing agent in plants, considered an antioxidant food ingredient. This study demonstrated that TA treatment significantly reduced lipid accumulation in human adipocytes and prevented high-fat diet induced obesity in zebrafish. Transcriptome sequencing revealed TA-activated fatty acid (FA) degradation and FA metabolism signaling pathways. Moreover, western blotting and quantitative polymerase chain reaction showed that TA inhibited the expression of long-chain acyl-CoA synthetase-4 (ACSL4). Overexpression of ACSL4 resulted in the reversal of TA beneficiary effects, indicating that the attenuated lipid accumulation of TA was regulated by ACSL4 expression. Limited proteolysis-mass spectrometry and microscale thermophoresis were then used to confirm hexokinase 2 (HK2) as a direct molecular target of TA. Thus, we demonstrated the molecular basis of TA in regulating lipid accumulation and gave the first evidence that TA may function through the HK2-ACSL4 axis.
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Affiliation(s)
- Jianfang Gao
- Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of General Practice, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhongxiao Zhang
- Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaohua Dong
- Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing Zhao
- Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhou Peng
- Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ling Zhang
- Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhongqing Xu
- Department of General Practice, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Liling Xu
- Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xingyun Wang
- Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xirong Guo
- Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Sowa I, Paduch R, Mołdoch J, Szczepanek D, Szkutnik J, Sowa P, Tyszczuk-Rotko K, Blicharski T, Wójciak M. Antioxidant and Cytotoxic Potential of Carlina vulgaris Extract and Bioactivity-Guided Isolation of Cytotoxic Components. Antioxidants (Basel) 2023; 12:1704. [PMID: 37760007 PMCID: PMC10525758 DOI: 10.3390/antiox12091704] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 08/28/2023] [Accepted: 08/30/2023] [Indexed: 09/29/2023] Open
Abstract
Carlina vulgaris is a poorly understood plant in the context of biological activity, despite its widespread application in ethnomedicine in numerous European countries. The aim of this study was to assess the cytotoxic potential of the plant against human colorectal adenocarcinoma (HT29) and to isolate the plant components linked to this effect. Ultra-high performance liquid chromatography with a high-resolution/quadrupole time-of-flight mass spectrometer (UHPLC-HR/QTOF/MS-PDA) was used for the phytochemical characterization of the extract. Liquid-liquid extraction and preparative chromatography were employed for fractionation purposes. Our investigation demonstrated that the ethyl acetate fraction from C. vulgaris showed significant cytotoxicity, and a bioactivity-guided approach led to the isolation of oxylipins, including traumatic acid, pinellic acid, and 9,10-dihydroxy-8-oxsooctadec-12-enic acid. The structures of the compounds were confirmed by nuclear magnetic resonance spectroscopy. Among these compounds, the last one exhibited significant cytotoxicity, though without selectivity, and traumatic acid was characterized by mild cytotoxicity. The cytotoxicity was linked to intracellular reactive oxygen species generation.
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Affiliation(s)
- Ireneusz Sowa
- Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland
| | - Roman Paduch
- Department of Virology and Immunology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, 19 Akademicka Street, 20-033 Lublin, Poland;
| | - Jarosław Mołdoch
- Department of Biochemistry and Crop Quality, Institute of Soil Science and Plant Cultivation, State Research Institute, 24-100 Puławy, Poland;
| | - Dariusz Szczepanek
- Chair and Department of Neurosurgery and Paediatric Neurosurgery, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Jacek Szkutnik
- Independent Unit of Functional Masticatory Disorders, Medical University of Lublin, 20-093 Lublin, Poland;
| | - Paweł Sowa
- Department of Otorhinolaryngology and Oncological Laryngology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 40-055 Katowice, Poland;
| | - Katarzyna Tyszczuk-Rotko
- Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Skłodowska University, 20-031 Lublin, Poland;
| | - Tomasz Blicharski
- Department of Orthopaedics and Rehabilitation, Medical University of Lublin, 20-954 Lublin, Poland;
| | - Magdalena Wójciak
- Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland
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Sowa I, Mołdoch J, Paduch R, Strzemski M, Szkutnik J, Tyszczuk-Rotko K, Dresler S, Szczepanek D, Wójciak M. Polyphenolic Composition of Carlina acaulis L. Extract and Cytotoxic Potential against Colorectal Adenocarcinoma and Cervical Cancer Cells. Molecules 2023; 28:6148. [PMID: 37630400 PMCID: PMC10458490 DOI: 10.3390/molecules28166148] [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: 07/28/2023] [Revised: 08/16/2023] [Accepted: 08/18/2023] [Indexed: 08/27/2023] Open
Abstract
Carlina acaulis is highly valued in the traditional medicine of many European countries for its diuretic, cholagogue, anthelmintic, laxative, and emetic properties. Moreover, practitioners of natural medicine indicate that it has anti-cancer potential. However, its phytochemistry is still little known. In the present study, the polyphenolic composition of the plant was investigated using ultra-high-performance liquid chromatography coupled with a high-resolution/quadrupole time-of-flight mass spectrometer (UHPLC-HR/QTOF/MS-PDA). The fractionation of the extract was carried out using liquid-liquid extraction and preparative chromatography techniques. Cytotoxicity was assessed based on neutral red and MTT assays. The obtained data showed that the species is rich in chlorogenic acids and C-glycosides of luteolin and apigenin. The total amount of chlorogenic acids was 12.6 mg/g. Among flavonoids, kaempferol dihexosidipentose and schaftoside were the most abundant, reaching approximately 3 mg/g, followed by isoorientin, vitexin-2-O-rhamnoside, and vicenin II, each with a content of approximately 2 mg/g. Furthermore, the cytotoxic potential of the plant against human colorectal adenocarcinoma (HT29) and human cervical cancer (HeLa) cells was investigated using the normal epithelial colon cell line (CCD 841CoTr) as a reference. It has been demonstrated that the ethyl acetate fraction was the most abundant in polyphenolic compounds and had the most promising anticancer activity. Further fractionation allowed for the obtaining of some subfractions that differed in phytochemical composition. The subfractions containing polyphenolic acids and flavonoids were characterized by low cytotoxicity against cancer and normal cell lines. Meanwhile, the subfraction with fatty acids was active and decreased the viability of HeLa and HT29 with minimal negative effects on CCD 841CoTr. The effect was probably linked to traumatic acid, which was present in the fraction at a concentration of 147 mg/g of dried weight. The research demonstrated the significant potential of C. acaulis as a plant with promising attributes, thus justifying further exploration of its biological activity.
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Affiliation(s)
- Ireneusz Sowa
- Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland; (M.S.); (S.D.)
| | - Jarosław Mołdoch
- Department of Biochemistry and Crop Quality, Institute of Soil Science and Plant Cultivation, State Research Institute, 24-100 Puławy, Poland;
| | - Roman Paduch
- Department of Virology and Immunology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, 19 Akademicka Street, 20-033 Lublin, Poland;
| | - Maciej Strzemski
- Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland; (M.S.); (S.D.)
| | - Jacek Szkutnik
- Independent Unit of Functional Masticatory Disorders, Medical University of Lublin, 20-093 Lublin, Poland;
| | - Katarzyna Tyszczuk-Rotko
- Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Skłodowska University in Lublin, 20-031 Lublin, Poland;
| | - Sławomir Dresler
- Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland; (M.S.); (S.D.)
| | - Dariusz Szczepanek
- Chair and Department of Neurosurgery and Paediatric Neurosurgery, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Magdalena Wójciak
- Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland; (M.S.); (S.D.)
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Safari-Alighiarloo N, Emami Z, Rezaei-Tavirani M, Alaei-Shahmiri F, Razavi S. Gut Microbiota and Their Associated Metabolites in Diabetes: A Cross Talk Between Host and Microbes-A Review. Metab Syndr Relat Disord 2023; 21:3-15. [PMID: 36301254 DOI: 10.1089/met.2022.0049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Dysbiosis of the gut microbiota's composition and function is important in developing insulin resistance and diabetes. Diabetes has also been linked to changes in the circulating and fecal metabolites. Evidence suggests the associations between the gut microbiota and the aberrant diabetes-related metabolome. Metabolites play a crucial role in the host-microbiota interactions. Researchers have used a combination of metagenomic and metabolomic approaches to investigate the relationships between gut microbial dysbiosis and metabolic abnormalities in diabetes. We summarized current discoveries on the associations between the gut microbiota and metabolites in type 1 diabetes, type 2 diabetes, and gestational diabetes mellitus in the scoping review. According to research, the gut microbiota changes might involve in the development of diabetes through modulating the host's metabolic pathways such as immunity, energy metabolism, lipid metabolism, and amino acid metabolism. These results add to our understanding of the interplay between the host and gut microbiota metabolism.
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Affiliation(s)
- Nahid Safari-Alighiarloo
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Emami
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Mostafa Rezaei-Tavirani
- Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fariba Alaei-Shahmiri
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Shabnam Razavi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Jabłońska – Trypuć A, Wiater J. Protective effect of plant compounds in pesticides toxicity. JOURNAL OF ENVIRONMENTAL HEALTH SCIENCE & ENGINEERING 2022; 20:1035-1045. [PMID: 36406617 PMCID: PMC9672277 DOI: 10.1007/s40201-022-00823-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 06/27/2022] [Accepted: 08/09/2022] [Indexed: 06/16/2023]
Abstract
INTRODUCTION The relationship between pesticide exposure and the occurrence of many chronic diseases, including cancer, is confirmed by literature data. METHODS In this review, through the analysis of more than 70 papers, we explore an increase in oxidative stress level caused by exposure to environmental pollutants and the protective effects of plant-origin antioxidants. RESULTS AND DISCUSSION One of the molecular mechanisms, by which pesticides affect living organisms is the induction of oxidative stress. However, recently many plant-based dietary ingredients with antioxidant properties have been considered as a chemopreventive substances due to their ability to remove free radicals. Such a food component must meet several conditions: eliminate free radicals, be easily absorbed and function at an appropriate physiological level. Its main function is to maintain the redox balance and minimize the cellular damage caused by ROS. Therefore, it should be active in aqueous solutions and membrane domains. These properties are characteristic for phenolic compounds and selected plant hormones. Phenolic compounds have proven antioxidant properties, while increasing number of compounds from the group of plant hormones with a very diverse chemical structure turn out to act as antioxidants, being potential food ingredients that can eliminate negative effects of pesticides.
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Affiliation(s)
- Agata Jabłońska – Trypuć
- Faculty of Civil Engineering and Environmental Sciences, Division of Chemistry, Biology and Biotechnology, Bialystok University of Technology, Wiejska 45E Street, 15-351 Białystok, Białystok, Poland
| | - Józefa Wiater
- Faculty of Civil Engineering and Environmental Sciences, Department of Agri-Food Engineering and Environmental Management, Bialystok University of Technology, Wiejska 45E Street, 15-351 Białystok, Białystok, Poland
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10
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Savchenko T, Degtyaryov E, Radzyukevich Y, Buryak V. Therapeutic Potential of Plant Oxylipins. Int J Mol Sci 2022; 23:14627. [PMID: 36498955 PMCID: PMC9741157 DOI: 10.3390/ijms232314627] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 11/19/2022] [Accepted: 11/21/2022] [Indexed: 11/25/2022] Open
Abstract
For immobile plants, the main means of protection against adverse environmental factors is the biosynthesis of various secondary (specialized) metabolites. The extreme diversity and high biological activity of these metabolites determine the researchers' interest in plants as a source of therapeutic agents. Oxylipins, oxygenated derivatives of fatty acids, are particularly promising in this regard. Plant oxylipins, which are characterized by a diversity of chemical structures, can exert protective and therapeutic properties in animal cells. While the therapeutic potential of some classes of plant oxylipins, such as jasmonates and acetylenic oxylipins, has been analyzed thoroughly, other oxylipins are barely studied in this regard. Here, we present a comprehensive overview of the therapeutic potential of all major classes of plant oxylipins, including derivatives of acetylenic fatty acids, jasmonates, six- and nine-carbon aldehydes, oxy-, epoxy-, and hydroxy-derivatives of fatty acids, as well as spontaneously formed phytoprostanes and phytofurans. The presented analysis will provide an impetus for further research investigating the beneficial properties of these secondary metabolites and bringing them closer to practical applications.
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Affiliation(s)
- Tatyana Savchenko
- Institute of Basic Biological Problems, Pushchino Scientific Center for Biological Research, Russian Academy of Sciences, 142290 Pushchino, Russia
| | - Evgeny Degtyaryov
- Institute of Basic Biological Problems, Pushchino Scientific Center for Biological Research, Russian Academy of Sciences, 142290 Pushchino, Russia
- Puschchino State Institute of Natural Sciences, Prospect Nauki st., 3, 142290 Pushchino, Russia
| | - Yaroslav Radzyukevich
- Institute of Basic Biological Problems, Pushchino Scientific Center for Biological Research, Russian Academy of Sciences, 142290 Pushchino, Russia
| | - Vlada Buryak
- Faculty of Biotechnology, Moscow State University, Leninskie Gory 1, str. 51, 119991 Moscow, Russia
- Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 142290 Pushchino, Russia
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11
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Vivek-Ananth RP, Sahoo AK, Srivastava A, Samal A. Virtual screening of phytochemicals from Indian medicinal plants against the endonuclease domain of SFTS virus L polymerase. RSC Adv 2022; 12:6234-6247. [PMID: 35424542 PMCID: PMC8982020 DOI: 10.1039/d1ra06702h] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 02/16/2022] [Indexed: 12/25/2022] Open
Abstract
Severe fever with thrombocytopenia syndrome virus (SFTSV) causes a highly infectious disease with reported mortality in the range 2.8% to 47%. The replication and transcription of the SFTSV genome is performed by L polymerase, which has both an RNA dependent RNA polymerase domain and an N-terminal endonuclease (endoN) domain. Due to its crucial role in the cap-snatching mechanism required for initiation of viral RNA transcription, the endoN domain is an ideal antiviral drug target. In this virtual screening study for the identification of potential inhibitors of the endoN domain of SFTSV L polymerase, we have used molecular docking and molecular dynamics (MD) simulation to explore the natural product space of 14 011 phytochemicals from Indian medicinal plants. After generating a heterogeneous ensemble of endoN domain structures reflecting conformational diversity of the corresponding active site using MD simulations, ensemble docking of the phytochemicals was performed against the endoN domain structures. Apart from the ligand binding energy from docking, our virtual screening workflow imposes additional filters such as drug-likeness, non-covalent interactions with key active site residues, toxicity and chemical similarity with other hits, to identify top 5 potential phytochemical inhibitors of endoN domain of SFTSV L polymerase. Further, the stability of the protein–ligand docked complexes for the top 5 potential inhibitors was analyzed using MD simulations. The potential phytochemical inhibitors, predicted in this study using contemporary computational methods, are expected to serve as lead molecules in future experimental studies towards development of antiviral drugs against SFTSV. Virtual screening of a large phytochemical library from Indian medicinal plants to identify potential endonuclease inhibitors against emerging virus SFTSV.![]()
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Affiliation(s)
- R P Vivek-Ananth
- The Institute of Mathematical Sciences (IMSc) Chennai 600113 India .,Homi Bhabha National Institute (HBNI) Mumbai 400094 India
| | - Ajaya Kumar Sahoo
- The Institute of Mathematical Sciences (IMSc) Chennai 600113 India .,Homi Bhabha National Institute (HBNI) Mumbai 400094 India
| | - Ashutosh Srivastava
- Discipline of Biological Engineering, Indian Institute of Technology Gandhinagar Gandhinagar 382355 India
| | - Areejit Samal
- The Institute of Mathematical Sciences (IMSc) Chennai 600113 India .,Homi Bhabha National Institute (HBNI) Mumbai 400094 India
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12
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Sinan KI, Akpulat U, Aldahish AA, Celik Altunoglu Y, Baloğlu MC, Zheleva-Dimitrova D, Gevrenova R, Lobine D, Mahomoodally MF, Etienne OK, Zengin G, Mahmud S, Capasso R. LC-MS/HRMS Analysis, Anti-Cancer, Anti-Enzymatic and Anti-Oxidant Effects of Boerhavia diffusa Extracts: A Potential Raw Material for Functional Applications. Antioxidants (Basel) 2021; 10:2003. [PMID: 34943106 PMCID: PMC8698501 DOI: 10.3390/antiox10122003] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 12/04/2021] [Accepted: 12/10/2021] [Indexed: 02/05/2023] Open
Abstract
Boerhavia diffusa is a great tropical plant and is widely used for various traditional purposes. In the present study, we examined the influence of solvents (dichloromethane, ethyl acetate, methanol and infusion (water)) on chemical composition and biological capabilities of B. diffusa. An UHPLC-HRMS method was used to determine the chemical characterization. The biological ability was examined for antioxidant, enzyme inhibitory and anti-cancer effects. To evaluate antioxidant effects, different chemical methods (ABTS, DPPH, CUPRAC, FRAP, metal chelating and phosphomolybdenum) were applied. With regard to enzyme inhibitory properties, cholinesterases, amylase, glucosidase and tyrosinase were used. The MDA-MB-231 breast cancer cell line was chosen to determine anticancer activity. Based on the UHPLC-HRMS analysis, 37 specialized metabolites were dereplicated and identified in the studied extracts. Results revealed the presence of 15 hydroxybenzoic, hydroxycinnamic, acylquinic acids, and their glycosides, one rotenoid, seven flavonoids, 12 fatty acids and two other glycosides. Among the tested extracts, the methanol extract showed a stronger antioxidant ability compared with other extracts. The methanol extract also showed the best inhibitory effects on tyrosinase and glucosidase. In the anti-cancer evaluation, the methanol extract showed stronger anticancer effects compared with water extract. In summary, our observations can contribute to the establishment of B. diffusa as a potential candidate for functional applications in the preparation.
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Affiliation(s)
- Kouadio Ibrahime Sinan
- Physiology and Biochemistry Research Laboratory, Department of Biology, Science Faculty, Selcuk University, Konya 42130, Turkey;
| | - Uğur Akpulat
- Department of Medical Biology, Faculty of Medicine, Kastamonu University, Kastamonu 37150, Turkey;
| | - Afaf A. Aldahish
- Department of Pharmacology and Toxicology, College of Pharmacy, King Khalid University, Abha 62529, Asir, Saudi Arabia;
| | - Yasemin Celik Altunoglu
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Kastamonu 37150, Turkey; (Y.C.A.); (M.C.B.)
| | - Mehmet Cengiz Baloğlu
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, Kastamonu 37150, Turkey; (Y.C.A.); (M.C.B.)
| | - Dimitrina Zheleva-Dimitrova
- Department of Pharmacognosy, Faculty of Pharmacy, Medical University-Sofia, 1431 Soifa, Bulgaria; (D.Z.-D.); (R.G.)
| | - Reneta Gevrenova
- Department of Pharmacognosy, Faculty of Pharmacy, Medical University-Sofia, 1431 Soifa, Bulgaria; (D.Z.-D.); (R.G.)
| | - Devina Lobine
- Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Réduit 80837, Mauritius; (D.L.); (M.F.M.)
| | - Mohamad Fawzi Mahomoodally
- Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Réduit 80837, Mauritius; (D.L.); (M.F.M.)
| | - Ouattara Katinan Etienne
- Laboratoire de Botanique, UFR Biosciences, Université Félix Houphouët-Boigny, Abidjan 00225, Côte d’Ivoire;
| | - Gokhan Zengin
- Physiology and Biochemistry Research Laboratory, Department of Biology, Science Faculty, Selcuk University, Konya 42130, Turkey;
| | - Shafi Mahmud
- Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh;
| | - Raffaele Capasso
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
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13
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Zhou Z, Zheng Z, Xiong X, Chen X, Peng J, Yao H, Pu J, Chen Q, Zheng M. Gut Microbiota Composition and Fecal Metabolic Profiling in Patients With Diabetic Retinopathy. Front Cell Dev Biol 2021; 9:732204. [PMID: 34722512 PMCID: PMC8554156 DOI: 10.3389/fcell.2021.732204] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 09/06/2021] [Indexed: 12/24/2022] Open
Abstract
Recent evidence suggests there is a link between metabolic diseases and gut microbiota. To investigate the gut microbiota composition and fecal metabolic phenotype in diabetic retinopathy (DR) patients. DNA was extracted from 50 fecal samples (21 individuals with type 2 diabetes mellitus-associated retinopathy (DR), 14 with type 2 diabetes mellitus but without retinopathy (DM) and 15 sex- and age-matched healthy controls) and then sequenced by high-throughput 16S rDNA analysis. Liquid chromatography mass spectrometry (LC-MS)-based metabolomics was simultaneously performed on the samples. A significant difference in the gut microbiota composition was observed between the DR and healthy groups and between the DR and DM groups. At the genus level, Faecalibacterium, Roseburia, Lachnospira and Romboutsia were enriched in DR patients compared to healthy individuals, while Akkermansia was depleted. Compared to those in the DM patient group, five genera, including Prevotella, were enriched, and Bacillus, Veillonella, and Pantoea were depleted in DR patients. Fecal metabolites in DR patients significantly differed from those in the healthy population and DM patients. The levels of carnosine, succinate, nicotinic acid and niacinamide were significantly lower in DR patients than in healthy controls. Compared to those in DM patients, nine metabolites were enriched, and six were depleted in DR patients. KEGG annotation revealed 17 pathways with differentially abundant metabolites between DR patients and healthy controls, and only two pathways with differentially abundant metabolites were identified between DR and DM patients, namely, the arginine-proline and α-linolenic acid metabolic pathways. In a correlation analysis, armillaramide was found to be negatively associated with Prevotella and Subdoligranulum and positively associated with Bacillus. Traumatic acid was negatively correlated with Bacillus. Our study identified differential gut microbiota compositions and characteristic fecal metabolic phenotypes in DR patients compared with those in the healthy population and DM patients. Additionally, the gut microbiota composition and fecal metabolic phenotype were relevant. We speculated that the gut microbiota in DR patients may cause alterations in fecal metabolites, which may contribute to disease progression, providing a new direction for understanding DR.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Minming Zheng
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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14
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Timolol induces necroptosis, apoptosis and senescence concentration-dependently in rabbit Limbal stem cells in vitro. Life Sci 2021; 277:119453. [PMID: 33798551 DOI: 10.1016/j.lfs.2021.119453] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/26/2021] [Accepted: 03/28/2021] [Indexed: 11/21/2022]
Abstract
Limbal stem cells (LSCs) are crucial for corneal transparency and vision. Any damages to LSCs might lead to limbal stem cell deficiency resulting in corneal opacification and even blindness. Here, we investigated the cytotoxicity of timolol and its underlying mechanisms in rabbit LSCs (rLSCs) in vitro. High concentrations of 0.5% and 0.25% timolol induced necroptosis in rLSCs to upregulate receptor interacting protein kinase (RIPK)1, RIPK3, mixed lineage kinase domain-like (MLKL) and phosphorylated MLKL along with downregulation of caspase-8 and caspase-2 within 4 h. While, median concentrations of 0.125% to 0.0625% timolol induced apoptosis in the rLSCs within 28 h. The apoptotic mechanism in the median-concentration timolol-treated rLSCs is probably via extrinsic apoptosis pathway by activating caspase-2, caspase-8 and caspase-3 and intrinsic apoptosis pathway triggered by excessive generation of ROS and subsequent DNA damage to upregulate Bax and Bad, downregulate Bcl-2 and Bcl-xL, subsequently disrupt mitochondrial membrane potential, cytosolically translocate cytochrome c and apoptosis-inducing factor, and activate caspase-9. In addition, low concentration of 0.03125% timolol induced senescence in the rLSCs by elevating ROS level and increasing number of senescence associated β-galactosidase positive cells at 28 h. Our findings reveal that timolol induces necroptosis, apoptosis and senescence concentration-dependently in rLSCs in vitro.
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15
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Onat B, Rosales-Solano H, Ferrier L, Pawliszyn J. Identification of the metabolites regulated in soybean-Rhizobia symbiosis through solid phase microextraction coupled with LC-MS. J Chromatogr A 2021; 1641:461934. [PMID: 33611117 DOI: 10.1016/j.chroma.2021.461934] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 01/20/2021] [Accepted: 01/21/2021] [Indexed: 12/12/2022]
Abstract
Legumes provide one of the uniquely nutrient-rich food sources to the population and are one of the primary field crops that play significant roles in agricultural sustainability. Inoculation with Bradyrhizobium japonicum is necessary for the high yield of leguminous crops, i.e. soybean. Nodulation of soybean by Bradyrhizobium japonicum is a complex process that is essential for cultivation of these legumes and external stress factors, such as draught and soil acidity, that influence the nodulation and crop yield. Alterations in the nodule metabolites are known to identify the type of stress that mitigates nodulation and lowers crop yield. Current techniques aimed at understanding the metabolic activities in the symbiont, such as in the case of metabolic regulations in varying nodule growth phases, rely on exhaustive techniques based on the removal of nodules or other plant tissue. Aiming to capture a more in-depth, accurate profile of this system without quenching the metabolic activity in the nodules, or removing the nodules, a workflow was prepared for the metabolite sampling through in vivo solid phase microextraction in thin film format (TF-SPME). This technique was followed by LC-QTOF-MS instrumental analysis with subsequent metabolite annotation and reference standard validation. Our approach is unique in terms of eliminating the effects that arise due to analyte partition coefficients. We show that the symbiont undergoes metabolic regulations throughout the cultivation period, displaying the efficacy of TF-SPME as a non-exhaustive sampling method that can be used as a tool to investigate the metabolic alterations in nodules. These alterations would potentially fingerprint the environmental effects on soybean yield.
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Affiliation(s)
- Bora Onat
- Department of Chemistry, University of Waterloo, Waterloo, ON, Canada
| | | | - Laura Ferrier
- (Member) Ontario Certified Crop Advisor Association, Elmira, ON, Canada
| | - Janusz Pawliszyn
- Department of Chemistry, University of Waterloo, Waterloo, ON, Canada.
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16
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Kerboua M, Ahmed MA, Samba N, Aitfella-Lahlou R, Silva L, Boyero JF, Raposo C, Lopez Rodilla JM. Phytochemical Investigation of New Algerian Lichen Species: Physcia Mediterranea Nimis. Molecules 2021; 26:1121. [PMID: 33672591 PMCID: PMC7924039 DOI: 10.3390/molecules26041121] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 02/17/2021] [Accepted: 02/18/2021] [Indexed: 11/16/2022] Open
Abstract
The present study provides new data concerning the chemical characterisation of Physcia mediterranea Nimis, a rare Mediterranean species belonging to the family Physciaceae. The phytochemical screening was carried out using GC-MS, HPLC-ESI-MS-MS, and NMR techniques. Hot extraction of n-hexane was carried out, followed by separation of the part insoluble in methanol: wax (WA-hex), from the part soluble in methanol (ME-hex). GC-MS analysis of the ME-hex part revealed the presence of methylbenzoic acids such as sparassol and atraric acid and a diterpene with a kaurene skeleton which has never been detected before in lichen species. Out of all the compounds identified by HPLC-ESI-MS-MS, sixteen compounds are common between WA-hex and ME-hex. Most are aliphatic fatty acids, phenolic compounds and depsides. The wax part is characterised by the presence of atranorin, a depside of high biological value. Proton 1H and carbon 13C NMR have confirmed its identification. Atranol, chloroatranol (depsides compound), Ffukinanolide (sesquiterpene lactones), leprolomin (diphenyl ether), muronic acid (triterpenes), and ursolic acid (triterpenes) have also been identified in ME-hex. The results suggested that Physcia mediterranea Nimis is a valuable source of bioactive compounds that could be useful for several applications as functional foods, cosmetics, and pharmaceuticals.
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Affiliation(s)
- Marwa Kerboua
- Laboratory of Vegetal Biology and Environment, Biology Department, Badji Mokhtar University, Annaba 23000, Algeria; (M.K.); (M.A.A.)
| | - Monia Ali Ahmed
- Laboratory of Vegetal Biology and Environment, Biology Department, Badji Mokhtar University, Annaba 23000, Algeria; (M.K.); (M.A.A.)
| | - Nsevolo Samba
- Chemistry Department, University of Beira Interior, 6201-001 Covilha, Portugal; (N.S.); (R.A.-L.); (L.S.)
- Department of Clinical Analysis and Public Health, University Kimpa Vita, Uige 77, Angola
| | - Radhia Aitfella-Lahlou
- Chemistry Department, University of Beira Interior, 6201-001 Covilha, Portugal; (N.S.); (R.A.-L.); (L.S.)
- Fiber Materials and Environmental Technologies (FibEnTech), University of Beira Interior, 6201-001 Covilhã, Portugal
- Laboratory of Valorisation and Conservation of Biological Resources, Biology Department, Faculty of Sciences, University M’Hamed Bougara, Boumerdes 35000, Algeria
| | - Lucia Silva
- Chemistry Department, University of Beira Interior, 6201-001 Covilha, Portugal; (N.S.); (R.A.-L.); (L.S.)
- Fiber Materials and Environmental Technologies (FibEnTech), University of Beira Interior, 6201-001 Covilhã, Portugal
| | - Juan F. Boyero
- Department of Analytical Chemistry, Nutrition and Food Science, Faculty of Chemistry, Chromatographic and mass analysis service (NUCLEUS), University of Salamanca, 37008 Salamanca, Spain; (J.F.B.); (C.R.)
| | - Cesar Raposo
- Department of Analytical Chemistry, Nutrition and Food Science, Faculty of Chemistry, Chromatographic and mass analysis service (NUCLEUS), University of Salamanca, 37008 Salamanca, Spain; (J.F.B.); (C.R.)
| | - Jesus Miguel Lopez Rodilla
- Chemistry Department, University of Beira Interior, 6201-001 Covilha, Portugal; (N.S.); (R.A.-L.); (L.S.)
- Fiber Materials and Environmental Technologies (FibEnTech), University of Beira Interior, 6201-001 Covilhã, Portugal
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17
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Jabłońska-Trypuć A, Krętowski R, Świderski G, Cechowska-Pasko M, Lewandowski W. Cichoric acid attenuates the toxicity of mesotrione. Effect on in vitro skin cell model. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2020; 77:103375. [PMID: 32279013 DOI: 10.1016/j.etap.2020.103375] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 03/17/2020] [Accepted: 03/20/2020] [Indexed: 06/11/2023]
Abstract
There is an important need to increase knowledge regarding the interactions between environmental contaminants and other compounds. Pesticides are an important group of food contaminants. By contrast, cichoric acid (CA) belongs to the category of desirable food ingredients with antioxidant and cytotoxic effects. The aim of the presented study was to test if CA may constitute a food ingredient, which eliminate stimulatory effect of pesticides on skin cancer cells and toxic effect of herbicides on fibroblasts. Therefore, we conducted cytotoxicity studies of environmentally relevant pesticide concentrations and the mixture of both compounds in melanoma and fibroblasts cells. We studied if CA combined with mesotrione change the oxidative stress parameters and apoptotic activity in treated cells. Obtained results indicate that CA exhibits cytotoxic activity against mesotrione-induced skin cancer development by influencing oxidative stress parameters and apoptosis. On the other hand CA inhibits prooxidative and proapoptotic activity of mesotrione in fibroblasts. Presented methods and obtained results could be a useful tool in the analysis of environmental contaminants toxicity and possible preventive activity of antioxidative plant- origin compounds.
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Affiliation(s)
- Agata Jabłońska-Trypuć
- Division of Chemistry, Biology and Biotechnology, Faculty of Civil Engineering and Environmental Sciences, Białystok University of Technology, Wiejska 45E Street, Białystok, 15-351, Poland.
| | - Rafał Krętowski
- Department of Pharmaceutical Biochemistry, Medical University of Bialystok, Białystok, 15-222, Poland.
| | - Grzegorz Świderski
- Division of Chemistry, Biology and Biotechnology, Faculty of Civil Engineering and Environmental Sciences, Białystok University of Technology, Wiejska 45E Street, Białystok, 15-351, Poland.
| | - Marzanna Cechowska-Pasko
- Department of Pharmaceutical Biochemistry, Medical University of Bialystok, Białystok, 15-222, Poland.
| | - Włodzimierz Lewandowski
- Division of Chemistry, Biology and Biotechnology, Faculty of Civil Engineering and Environmental Sciences, Białystok University of Technology, Wiejska 45E Street, Białystok, 15-351, Poland.
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18
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Possible Protective Effects of TA on the Cancerous Effect of Mesotrione. Nutrients 2020; 12:nu12051343. [PMID: 32397133 PMCID: PMC7285202 DOI: 10.3390/nu12051343] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 05/01/2020] [Accepted: 05/06/2020] [Indexed: 01/10/2023] Open
Abstract
The interaction of different food ingredients is now a very important and often emerging topic of research. Pesticides and their breakdown products, which may be carcinogenic, are one of the frequently occurring food contaminants. Compounds like traumatic acid (TA), which originates from plants, are beneficial, antioxidant, and anticancer food ingredients. Previously obtained results from our research group indicated antioxidative in normal human fibroblasts and prooxidative in cancer cells activity of TA. Since the literature data show an undoubted connection between the presence of pesticides in food and the increased incidence of different types of cancers, we attempted to clarify whether TA can abolish the effect of mesotrione stimulating the growth of cancer cells. In order to study the influence of mesotrione on breast cancer cells, we decided to carry out cytotoxicity studies of environmentally significant herbicide concentrations. We also analyzed the cytotoxicity of TA and mixtures of these two compounds. After selecting the most effective concentrations of both components tested, we conducted analyses of oxidative stress parameters and apoptosis in ZR-75-1 cells. The obtained results allow us to conclude that traumatic acid by stimulating oxidative stress and apoptosis contributes to inhibiting the growth and development of cells of the ZR-75-1 line strengthened by mesotrione. This may mean that TA is a compound with pro-oxidative and proapoptotic effects in cancer cells whose development and proliferation are stimulated by the presence of mesotrione. The presented results may be helpful in answering the question of whether herbicides and their residues in edibles may constitute potential threat for people diagnosed with cancer and whether compounds with proven pro-oxidative effects on cancer cells can have potential cytoprotective functions.
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Su W, Zhao J, Fan TJ. Dose- and Time-Dependent Cytotoxicity of Carteolol in Corneal Endothelial Cells and the Underlying Mechanisms. Front Pharmacol 2020; 11:202. [PMID: 32210806 PMCID: PMC7068677 DOI: 10.3389/fphar.2020.00202] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 02/14/2020] [Indexed: 01/19/2023] Open
Abstract
Carteolol is a non-selective β-adrenoceptor antagonist used for the treatment of glaucoma, and its abuse might be cytotoxic to the cornea. However, its cytotoxicity and underlying mechanisms need to be elucidated. Herein, we used an in vivo model of feline corneas and an in vitro model of human corneal endothelial cells (HCECs), respectively. In vivo results displayed that 2% carteolol (clinical dosage) could induce monolayer density decline and breaking away of feline corneal endothelial (FCE) cells. An in vitro model of HCECs that were treated dose-dependently (0.015625–2%) with carteolol for 2–28 h, resulted in morphological abnormalities, declining in cell viability and elevating plasma membrane (PM) permeability in a dose- and time- dependent manner. High-dose (0.5–2%) carteolol treatment induced necrotic characteristics with uneven distribution of chromatin, marginalization and dispersed DNA degradation, inactivated caspase-2/-8, and increased RIPK1, RIPK3, MLKL, and pMLKL expression. The results suggested that high-dose carteolol could induce necroptosis via the RIPK/MLKL pathway. While low-dose (0.015625–0.25%) carteolol induced apoptotic characteristics with chromatin condensation, typical intranucleosomal DNA laddering patterns, G1 cell-cycle arrest, phosphatidylserine (PS) externalization, and apoptotic body formation in HCECs. Meanwhile, 0.25% carteolol treatment resulted in activated caspase-2, -3, -8, and -9, downregulation of Bcl-2 and Bcl-xL, upregulation of Bax and Bad, ΔΨm disruption, and release of cytoplasmic cytochrome c (Cyt.c) and AIF into the cytoplasm. These observations suggested that low-dose carteolol could induce apoptosis via a caspase activated and mitochondrial-dependent pathway. These results suggested that carteolol should be used carefully, as low as 0.015625% cartelol caused apoptotic cell death in HCECs in vitro.
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Affiliation(s)
- Wen Su
- Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Jun Zhao
- Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences, Ocean University of China, Qingdao, China
| | - Ting-Jun Fan
- Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences, Ocean University of China, Qingdao, China
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You XG, Fan TJ, Jiang GJ. Phenylephrine induces necroptosis and apoptosis in corneal epithelial cells dose- and time-dependently. Toxicology 2019; 428:152305. [PMID: 31605733 DOI: 10.1016/j.tox.2019.152305] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Revised: 09/13/2019] [Accepted: 10/02/2019] [Indexed: 11/19/2022]
Abstract
In the present study, the toxicity of phenylephrine, a selective α1-adrenergic receptor agonist, in corneal epithelial cells and its underlying mechanisms were investigated using an in vitro model of human corneal epithelial cells (HCEPCs) and an in vivo model of New Zealand white rabbit corneas. The HCEPCs treated with phenylephrine at concentrations from 10% to 0.078125% displayed abnormal morphology, decline of cell viability and elevation of plasma membrane permeability time- and dose-dependently. Moreover, 10%-1.25% phenylephrine induce necrosis characteristics of marginalization and uneven distribution of chromatin through up-regulation of RIPK1, RIPK3 and MLKL along with inactivation of caspase-8 and caspase-2, whereas 0.625% phenylephrine induced condensed chromatin, S phase arrest, phosphatidylserine externalization, DNA fragmentation and apoptotic body formation in the HCECs through activation of caspase-2, -8, -9 and -3 as well as down-regulation of Bcl-2, up-regulation of Bad, ΔΨm disruption and release of cytochrome c and AIF into cytosol. At last, 10% phenylephrine induced destruction of the corneal epithelia and apoptosis of corneal epithelial cells in rabbit corneas. In conclusion, 10% to 1.25% phenylephrine cause necroptosis via RIPK1-RIPK3-MLKL axis and 0.625% phenylephrine induce apoptosis via a mitochondrion-dependent and death receptor-mediated signal pathway in HCEPCs.
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Affiliation(s)
- Xin-Guo You
- Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences, Ocean University of China, Qingdao, Shandong Province 266003, PR China
| | - Ting-Jun Fan
- Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences, Ocean University of China, Qingdao, Shandong Province 266003, PR China
| | - Guo-Jian Jiang
- Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences, Ocean University of China, Qingdao, Shandong Province 266003, PR China.
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Jabłońska-Trypuć A, Wydro U, Serra-Majem L, Wołejko E, Butarewicz A. The Analysis of Bifenox and Dichlobenil Toxicity in Selected Microorganisms and Human Cancer Cells. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16214137. [PMID: 31717849 PMCID: PMC6862445 DOI: 10.3390/ijerph16214137] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 10/14/2019] [Accepted: 10/24/2019] [Indexed: 12/15/2022]
Abstract
Bifenox and Dichlobenil belong to the commonly used in Poland in agriculture group of herbicides and their residues are often detected in the environment. They are poorly known regarding their possible carcinogenic and antibacterial effect at the cellular level. Therefore, we decided to study their activity in bacterial strains Aliivibrio fisheri, E. coli, P. aeruginosa, and C. albicans (yeast) and human cancer ZR-75-1 cells. Compounds under study exhibit stimulatory effect on analyzed bacterial strains. The study performed on mammalian cells better reflects the influence of environmental pollutants on human organism, therefore we evaluated the effect of herbicides on ZR-75-1 cells. Cells viability, apoptosis and selected oxidative stress parameters in ZR-75-1 cells were investigated. Both analyzed substances exhibit stimulatory effects on analyzed parameters, however they do not stimulate apoptosis which correlate positively with the induction of oxidative stress. Bifenox and Dichlobenil enhance oxidative stress parameters by the generation of high levels of ROS, which can lead to their adaptation and resistance to the standard treatment regimen.
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Affiliation(s)
- Agata Jabłońska-Trypuć
- Division of Chemistry, Biology and Biotechnology, Faculty of Civil Engineering and Environmental Engineering, Bialystok University of Technology, 15-351 Białystok, Poland; (U.W.); (E.W.); (A.B.)
- Correspondence:
| | - Urszula Wydro
- Division of Chemistry, Biology and Biotechnology, Faculty of Civil Engineering and Environmental Engineering, Bialystok University of Technology, 15-351 Białystok, Poland; (U.W.); (E.W.); (A.B.)
| | - Lluis Serra-Majem
- Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, 35001 Las Palmas de Gran Canaria, Spain;
| | - Elżbieta Wołejko
- Division of Chemistry, Biology and Biotechnology, Faculty of Civil Engineering and Environmental Engineering, Bialystok University of Technology, 15-351 Białystok, Poland; (U.W.); (E.W.); (A.B.)
| | - Andrzej Butarewicz
- Division of Chemistry, Biology and Biotechnology, Faculty of Civil Engineering and Environmental Engineering, Bialystok University of Technology, 15-351 Białystok, Poland; (U.W.); (E.W.); (A.B.)
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