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Piras F, Sogos V, Pollastro F, Appendino G, Rosa A. Arzanol, a natural phloroglucinol α-pyrone, protects HaCaT keratinocytes against H 2O 2-induced oxidative stress, counteracting cytotoxicity, reactive oxygen species generation, apoptosis, and mitochondrial depolarization. J Appl Toxicol 2024; 44:720-732. [PMID: 38152000 DOI: 10.1002/jat.4570] [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: 09/20/2023] [Revised: 11/08/2023] [Accepted: 11/22/2023] [Indexed: 12/29/2023]
Abstract
Skin oxidative stress results in structural damage, leading to premature senescence, and pathological conditions such as inflammation and cancer. The plant-derived prenylated pyrone-phloroglucinol heterodimer arzanol, isolated from Helichrysum italicum ssp. microphyllum (Willd.) Nyman aerial parts, exhibits anti-inflammatory, anticancer, antimicrobial, and antioxidant activities. This study explored the arzanol protection against hydrogen peroxide (H2O2) induced oxidative damage in HaCaT human keratinocytes in terms of its ability to counteract cytotoxicity, reactive oxygen species (ROS) generation, apoptosis, and mitochondrial membrane depolarization. Arzanol safety on HaCaT cells was preliminarily examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and microscopic observation. The arzanol pre-incubation (5-100 μM, for 24 h) did not induce cytotoxicity and morphological alterations. The phloroglucinol, at 50 μM, significantly protected keratinocytes against cytotoxicity induced by 2 h-incubation with 2.5 and 5 mM H2O2, decreased cell ROS production induced by 1 h-exposure to all tested H2O2 concentrations (0.5-5 mM), as determined by the 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) assay, and lipid peroxidation (thiobarbituric acid reactive substances [TBARS] method). The 2-h incubation of keratinocytes with H2O2 determined a significant increase of apoptotic cells versus control cells, evaluated by NucView® 488 assay, from the dose of 2.5 mM. Moreover, an evident mitochondrial membrane potential depolarization, monitored by fluorescent mitochondrial dye MitoView™ 633, was assessed at 5 mM H2O2. Arzanol pre-treatment (50 μM) exerted a strong significant protective effect against apoptosis, preserving the mitochondrial membrane potential of HaCaT cells at the highest H2O2 concentrations. Our results validate arzanol as an antioxidant agent for the prevention/treatment of skin oxidative-related disorders, qualifying its potential use for cosmeceutical and pharmaceutical applications.
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Affiliation(s)
- Franca Piras
- Department of Biomedical Sciences, University of Cagliari, Monserrato, 09042, Italy
| | - Valeria Sogos
- Department of Biomedical Sciences, University of Cagliari, Monserrato, 09042, Italy
| | - Federica Pollastro
- Department of Pharmaceutical Sciences, University of Eastern Piedmont, Novara, 28100, Italy
- PlantaChem S.r.l.s, Novara, 28100, Italy
| | - Giovanni Appendino
- Department of Pharmaceutical Sciences, University of Eastern Piedmont, Novara, 28100, Italy
| | - Antonella Rosa
- Department of Biomedical Sciences, University of Cagliari, Monserrato, 09042, Italy
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Forouzanfar F, Tabatabaei Z, Emami SA, Ayati Z, Tayarani‐Najaran Z. Protective effects of fruit extract of Rosa canina and quercetin on human umbilical vein endothelial cell injury induced by hydrogen peroxide. Food Sci Nutr 2023; 11:7618-7625. [PMID: 38107098 PMCID: PMC10724588 DOI: 10.1002/fsn3.3681] [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: 05/12/2023] [Revised: 08/26/2023] [Accepted: 08/28/2023] [Indexed: 12/19/2023] Open
Abstract
The Nastaran plant, with the scientific name of Rosa canina, has been used since ancient times as a plant with medicinal properties. In the present study, human umbilical vein endothelial cells (HUVECs) were used to examine the protective effects of R. canina fruit extract (RCFE) and its flavonoid ingredient (quercetin) against H2O2-induced cell injury. RCFE (1.25-20 μg/mL) and quercetin (1.25-20 μM) were exposed to H2O2-oxidizing agent (1 and 2 mM) and the protective effect was examined on HUVEC cells by Alamar Blue test. The amount of intracellular reactive oxygen species (ROS) was measured by using DCFDA reagent by fluorimetric method. The effects of RCFE and quercetin on cell apoptosis were studied by staining with hypotonic PI solution and flow cytometry. The amount of PARP and survivin involved in the apoptotic process was measured using the western blot analysis. The results of the Alamar Blue test showed that RCFE and quercetin could reduce the toxicity of H2O2. RCFE and quercetin were able to significantly increase cell viability against H2O2. Also, it was found that RCFE and quercetin reduced the production of ROS by H2O2. It was found that RCFE and quercetin reduced the apoptosis and sub-G1 peak area in flow histogram after exposure of cells to H2O2. Based on western blot results, pretreatment with RCFE and quercetin could significantly increase survivin protein after exposure of cells to H2O2. Also, RCFE and quercetin could significantly reduce the amount of cleaved PARP after exposure of cells to H2O2. RCFE and its ingredient (quercetin) can be considered a promising source of phytochemicals in the prevention of cardiovascular diseases.
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Affiliation(s)
- Fatemeh Forouzanfar
- Department of Neuroscience, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
| | - Zeynab Tabatabaei
- Department of Traditional Pharmacy, School of PharmacyMashhad University of Medical SciencesMashhadIran
- Medical Toxicology Research CenterMashhad University of Medical SciencesMashhadIran
| | - Seyed Ahmad Emami
- Department of Traditional Pharmacy, School of PharmacyMashhad University of Medical SciencesMashhadIran
| | - Zahra Ayati
- Department of Traditional Pharmacy, School of PharmacyMashhad University of Medical SciencesMashhadIran
- Western Sydney UniversityPenrithAustralia
| | - Zahra Tayarani‐Najaran
- Targeted Drug Delivery Research Center, Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran
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Farshori NN, Siddiqui MA, Al-Oqail MM, Al-Sheddi ES, Al-Massarani SM, Ahamed M, Ahmad J, Al-Khedhairy AA. Copper Oxide Nanoparticles Exhibit Cell Death Through Oxidative Stress Responses in Human Airway Epithelial Cells: a Mechanistic Study. Biol Trace Elem Res 2022; 200:5042-5051. [PMID: 35000107 DOI: 10.1007/s12011-022-03107-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 01/04/2022] [Indexed: 11/02/2022]
Abstract
Copper oxide nanoparticles (CuONPs) are purposefully used to inhibit the growth of bacteria, algae, and fungi. Several studies on the beneficial and harmful effects of CuONPs have been conducted in vivo and in vitro, but there are a few studies that explain the toxicity of CuONPs in human airway epithelial cells (HEp-2). As a result, the purpose of this study is to look into the dose-dependent toxicity of CuONPs in HEp-2 cells. After 24 h of exposure to 1-40 µg/ml CuONPs, the MTT and neutral red assays were used to test for cytotoxicity. To determine the mechanism(s) of cytotoxicity in HEp-2 cells, additional oxidative stress assays (LPO and GSH), the amount of ROS produced, the loss of MMP, caspase enzyme activities, and apoptosis-related genes were performed using qRT-PCR. CuONPs exhibited dose-dependent cytotoxicity in HEp-2 cells, with an IC50 value of ~ 10 μg/ml. The morphology of HEp-2 cells was also altered in a dose-dependent manner. The involvement of oxidative stress in CuONP-induced cytotoxicity was demonstrated by increased LPO levels and ROS generation, as well as decreased levels of GSH and MMP. Furthermore, activated caspase enzymes and altered apoptotic genes support CuONPs' ability to induce apoptosis in HEp-2 cells. Overall, this study demonstrated that CuONPs can cause apoptosis in HEp-2 cells via oxidative stress; therefore, CuONPs may pose a risk to human health and should be handled and used with caution.
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Affiliation(s)
- Nida N Farshori
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 11495, Saudi Arabia
| | - Maqsood A Siddiqui
- DNA Research Chair, Zoology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
| | - Mai M Al-Oqail
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 11495, Saudi Arabia
| | - Ebtesam S Al-Sheddi
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 11495, Saudi Arabia
| | - Shaza M Al-Massarani
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 11495, Saudi Arabia
| | - Maqusood Ahamed
- King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, 11451, Saudi Arabia
| | - Javed Ahmad
- DNA Research Chair, Zoology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia
| | - Abdulaziz A Al-Khedhairy
- DNA Research Chair, Zoology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia
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Dalli M, Bekkouch O, Azizi SE, Azghar A, Gseyra N, Kim B. Nigella sativa L. Phytochemistry and Pharmacological Activities: A Review (2019-2021). Biomolecules 2021; 12:20. [PMID: 35053168 PMCID: PMC8773974 DOI: 10.3390/biom12010020] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 12/16/2021] [Accepted: 12/20/2021] [Indexed: 12/23/2022] Open
Abstract
Medicinal and aromatic plants are mainly characterized by the presence of different bioactive compounds which exhibit various therapeutic activities. In order to investigate the different pharmacological properties of different Nigella sativa extracts, a multitude of research articles published in the period between 2019 and 2021 were obtained from different databases (Scopus, Science Direct, PubMed, and Web of Science), and then explored and analyzed. The analysis of the collected articles allows us to classify the phytochemicals and the pharmacological activities through their underlying molecular mechanisms, as well as to explore the pharmacological activities exhibited by several identified compounds in Nigella sativa which allow a better understanding, and better elucidation, of the bioactive compounds responsible for the pharmacological effects. Also shown are the existence of other bioactive compounds that are still unexplored and could be of great interest. This review could be taken as a guide for future studies in the field.
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Affiliation(s)
- Mohammed Dalli
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, University Mohammed the First, P.O. Box 524, 60000 Oujda, Morocco; (O.B.); (S.-e.A.); (A.A.); (N.G.)
| | - Oussama Bekkouch
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, University Mohammed the First, P.O. Box 524, 60000 Oujda, Morocco; (O.B.); (S.-e.A.); (A.A.); (N.G.)
| | - Salah-eddine Azizi
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, University Mohammed the First, P.O. Box 524, 60000 Oujda, Morocco; (O.B.); (S.-e.A.); (A.A.); (N.G.)
| | - Ali Azghar
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, University Mohammed the First, P.O. Box 524, 60000 Oujda, Morocco; (O.B.); (S.-e.A.); (A.A.); (N.G.)
| | - Nadia Gseyra
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, University Mohammed the First, P.O. Box 524, 60000 Oujda, Morocco; (O.B.); (S.-e.A.); (A.A.); (N.G.)
| | - Bonglee Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea
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Cao Y. Introduction to special issue endothelial cells in toxicology: Current status and future perspectives. J Appl Toxicol 2021; 41:656-658. [PMID: 33686682 DOI: 10.1002/jat.4163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/01/2021] [Accepted: 03/01/2021] [Indexed: 11/10/2022]
Affiliation(s)
- Yi Cao
- Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang, China
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