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Gebremedin BD, Asfaw BT, Mengesha WA, Abebe KA. Biochemical Characterization of Ethiopian Black Cumin ( Nigella sativa L.). INTERNATIONAL JOURNAL OF FOOD SCIENCE 2024; 2024:2746560. [PMID: 39185325 PMCID: PMC11343625 DOI: 10.1155/2024/2746560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 07/17/2024] [Accepted: 08/02/2024] [Indexed: 08/27/2024]
Abstract
Black cumin (Nigella sativa L.) seed oil has been used for its medicinal and aromatic values. Some studies revealed the presence of variability among N. sativa genotypes in seed oil content and yield. In Ethiopia, very few studies were conducted to investigate the variability of N. sativa genotypes by using biochemical traits. Thus, this study was conducted at Debre Zeit and Kulumsa Agricultural Research Centers' experimental sites under field conditions during the 2021 cropping season to investigate the variability of Ethiopian N. sativa genotypes based on biochemical traits. Sixty-four genotypes were used and arranged in an 8 × 8 simple lattice design with two replications. Essential oils (EOs) and fixed oils were extracted by the respective methods of hydro distillation and solvent extraction. The univariate, bivariate, and multivariate analyses of the collected data were performed. Combined analysis of variance (ANOVA) revealed significant differences among genotypes in fixed oil yield per hectare (FOY), EO content (EOC), and EO yield per hectare (EOY). EOY had a significant positive correlation with FOY and EOC. It is expected to improve all biochemical traits by 17.39%-94.62% over the improved varieties by selection of the top 5% landraces. Therefore, genotypes 90504, 219970, and 013_ATH were the top 5% best performed landraces by FOY and EOY over the improved varieties. So, through selection, it would also be possible to improve the studied biochemical traits of the genotypes. The principal component (PC) analysis (PCA) of four biochemical traits showed 85.86% of the total variance captured by the first two PCs. EOY and FOY were the main contributor traits to the variation in the first PC, whereas FOC and EOC were the main contributor traits to the variation in the second PC. The genotypes were grouped into three different clusters based on four biochemical traits with significant intercluster distance. This showed that there was sufficient diversity among the genotypes which can be exploited for the future N. sativa improvement program in Ethiopia.
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Affiliation(s)
- Basazinew Degu Gebremedin
- Wondo Genet Agricultural Research CenterEthiopian Institute of Agricultural Research, P. O. Box 198, Shashemene, Ethiopia
- School of Plant and Horticultural ScienceHawassa University, P. O. Box 05, Hawassa, Ethiopia
| | - Bizuayehu Tesfaye Asfaw
- School of Plant and Horticultural ScienceHawassa University, P. O. Box 05, Hawassa, Ethiopia
| | - Wendawek Abebe Mengesha
- Department of MolecularCellular and Microbial BiologyAddis Ababa University, P. O. Box 3434, Addis Ababa, Ethiopia
| | - Kebebew Assefa Abebe
- Debre Zeit Agricultural Research CenterEthiopian Institute of Agricultural Research, P. O. Box 32, Debre Zeit, Ethiopia
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Khodaie SA, Razavi R, Nikkhah H, Namiranian N, Kamalinejad M. Nigella sativa L. and its bioactive and nutraceutical components in the management of diabetic peripheral neuropathy. Inflammopharmacology 2024:10.1007/s10787-024-01528-6. [PMID: 39143432 DOI: 10.1007/s10787-024-01528-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 07/05/2024] [Indexed: 08/16/2024]
Abstract
Diabetes-induced hyperglycemia leads to excessive production of oxygen free radicals, inflammatory cytokines, and oxidative stress, which initiates diabetic peripheral neuropathy (DPN). Currently, this condition affects 20% of adults with diabetes. Despite significant advances in the treatment of diabetes, the incidence of its complications, including DPN, is still high. Thus, there is a growing research interest in developing more effective and treatment approaches with less side effects for diabetes and its complications. Nigella sativa L. (NS) has received much research attention as an antioxidant, anti-yperglycemic factor, and anti-inflammatory agent. This natural compound demonstrates its antidiabetic neuropathy effect through various pathways, including the reduction of lipid peroxidation, the enhancement of catalase and superoxide dismutase enzyme activity, and the decrease in inflammatory cytokine levels. The present review focuses on the bioactive and nutraceutical components of black cumin (Nigella sativa L.) and their effects on DPN. In addition, we have also summarized the findings obtained from several experimental and clinical studies regarding the antidiabetic neuropathy effect of NS in animal models and human subjects.
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Affiliation(s)
- Seyed-Ali Khodaie
- Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Roghaye Razavi
- Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Haniyeh Nikkhah
- Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nasim Namiranian
- Community & Preventive Medicine, Yazd Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammad Kamalinejad
- School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Behdane Baran Salem Abi Company, Tehran, Iran.
- AB Pharma inc267 Esplanade West, North Vancouver, BC, Canada.
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Nyulas KI, Simon-Szabó Z, Pál S, Fodor MA, Dénes L, Cseh MJ, Barabás-Hajdu E, Csipor B, Szakács J, Preg Z, Germán-Salló M, Nemes-Nagy E. Cardiovascular Effects of Herbal Products and Their Interaction with Antihypertensive Drugs-Comprehensive Review. Int J Mol Sci 2024; 25:6388. [PMID: 38928095 PMCID: PMC11203894 DOI: 10.3390/ijms25126388] [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: 04/29/2024] [Revised: 06/05/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024] Open
Abstract
Hypertension is a highly prevalent population-level disease that represents an important risk factor for several cardiovascular complications and occupies a leading position in mortality statistics. Antihypertensive therapy includes a wide variety of drugs. Additionally, the potential antihypertensive and cardioprotective effects of several phytotherapy products have been evaluated, as these could also be a valuable therapeutic option for the prevention, improvement or treatment of hypertension and its complications. The present review includes an evaluation of the cardioprotective and antihypertensive effects of garlic, Aloe vera, green tea, Ginkgo biloba, berberine, ginseng, Nigella sativa, Apium graveolens, thyme, cinnamon and ginger, and their possible interactions with antihypertensive drugs. A literature search was undertaken via the PubMed, Google Scholar, Embase and Cochrane databases. Research articles, systematic reviews and meta-analyses published between 2010 and 2023, in the English, Hungarian, and Romanian languages were selected.
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Affiliation(s)
- Kinga-Ilona Nyulas
- Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540139 Târgu Mureș, Romania
| | - Zsuzsánna Simon-Szabó
- Department of Pathophysiology, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540139 Târgu Mureș, Romania
| | - Sándor Pál
- Department of Laboratory Medicine, Department of Transfusion Medicine, Medical School, University of Pécs, 7622 Pécs, Hungary
| | - Márta-Andrea Fodor
- Department of Laboratory Medicine, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540139 Târgu Mureș, Romania
| | - Lóránd Dénes
- Department of Anatomy and Embryology, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540139 Târgu Mureș, Romania
| | - Margit Judit Cseh
- Master Program of Nutrition and Dietetics, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540139 Târgu Mureș, Romania
| | - Enikő Barabás-Hajdu
- Department of Cell Biology and Microbiology, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540139 Târgu Mureș, Romania
| | - Bernadett Csipor
- Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540139 Târgu Mureș, Romania
| | - Juliánna Szakács
- Department of Biophysics, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540139 Târgu Mureș, Romania
| | - Zoltán Preg
- Department of Family Medicine, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540139 Târgu Mureș, Romania
| | - Márta Germán-Salló
- Department of Internal Medicine III, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540139 Târgu Mureș, Romania
| | - Enikő Nemes-Nagy
- Department of Chemistry and Medical Biochemistry, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540139 Târgu Mureș, Romania;
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Park M, Yi JM, Kim NS, Lee SY, Lee H. Effect of Poria cocos Terpenes: Verifying Modes of Action Using Molecular Docking, Drug-Induced Transcriptomes, and Diffusion Network Analyses. Int J Mol Sci 2024; 25:4636. [PMID: 38731856 PMCID: PMC11083729 DOI: 10.3390/ijms25094636] [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: 03/28/2024] [Revised: 04/18/2024] [Accepted: 04/21/2024] [Indexed: 05/13/2024] Open
Abstract
We characterized the therapeutic biological modes of action of several terpenes in Poria cocos F.A Wolf (PC) and proposed a broad therapeutic mode of action for PC. Molecular docking and drug-induced transcriptome analysis were performed to confirm the pharmacological mechanism of PC terpene, and a new analysis method, namely diffusion network analysis, was proposed to verify the mechanism of action against Alzheimer's disease. We confirmed that the compound that exists only in PC has a unique mechanism through statistical-based docking analysis. Also, docking and transcriptomic analysis results could reflect results in clinical practice when used complementarily. The detailed pharmacological mechanism of PC was confirmed by constructing and analyzing the Alzheimer's disease diffusion network, and the antioxidant activity based on microglial cells was verified. In this study, we used two bioinformatics approaches to reveal PC's broad mode of action while also using diffusion networks to identify its detailed pharmacological mechanisms of action. The results of this study provide evidence that future pharmacological mechanism analysis should simultaneously consider complementary docking and transcriptomics and suggest diffusion network analysis, a new method to derive pharmacological mechanisms based on natural complex compounds.
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Affiliation(s)
- Musun Park
- Korean Medicine (KM) Data Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea
| | - Jin-Mu Yi
- KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea; (J.-M.Y.); (N.S.K.)
| | - No Soo Kim
- KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea; (J.-M.Y.); (N.S.K.)
| | - Seo-Young Lee
- KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea;
| | - Haeseung Lee
- College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea;
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Aslani MR, Saadat S, Boskabady MH. Comprehensive and updated review on anti-oxidant effects of Nigella sativa and its constituent, thymoquinone, in various disorders. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2024; 27:923-951. [PMID: 38911247 PMCID: PMC11193497 DOI: 10.22038/ijbms.2024.75985.16453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 04/24/2024] [Indexed: 06/25/2024]
Abstract
Several pharmacological effects were described for Nigella sativa (N. sativa) seed and it has been used traditionally to treat various diseases. In this review article, the updated and comprehensive anti-oxidant effects of N. sativa and its main constituent, thymoquinone (TQ), on various disorders are described. The relevant articles were retrieved through PubMed, Science Direct, and Scopus up to December 31, 2023. Various extracts and essential oils of N. sativa showed anti-oxidant effects on cardiovascular, endocrine, gastrointestinal and liver, neurologic, respiratory, and urogenital diseases by decreasing and increasing various oxidant and anti-oxidant marketers, respectively. The main constituent of the plant, TQ, also showed similar anti-oxidant effects as the plant itself. The anti-oxidant effects of different extracts and essential oils of N. sativa were demonstrated in various studies which were perhaps due to the main constituent of the plant, TQ. The findings of this review article suggest the possible therapeutic effect of N. sativa and TQ in oxidative stress disorders.
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Affiliation(s)
- Mohammad Reza Aslani
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Lung Inflammatory Diseases Research Center, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Saeideh Saadat
- Department of Physiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mohammad Hossein Boskabady
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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6
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Ghasemi F, Nili-Ahmadabadi A, Omidifar N, Nili-Ahmadabadi M. Protective potential of thymoquinone against cadmium, arsenic, and lead toxicity: A short review with emphasis on oxidative pathways. J Appl Toxicol 2023; 43:1764-1777. [PMID: 36872630 DOI: 10.1002/jat.4459] [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: 07/31/2022] [Revised: 02/13/2023] [Accepted: 02/27/2023] [Indexed: 03/07/2023]
Abstract
Heavy metals are among the most important environmental pollutions used in various industries. Their extensive use has increased human susceptibility to different chronic diseases. Toxic metal exposure, especially cadmium, arsenic, and lead, causes oxidative damages, mitochondrial dysfunction, and genetic and epigenetic modifications. Meanwhile, thymoquinone (TQ) is an effective component of Nigella sativa oil that plays an important role in preventing the destructive effects of heavy metals. The present review discusses how TQ can protect various tissues against oxidative damage of heavy metals. This review is based on the research reported about the protective effects of TQ in the toxicity of heavy metals, approximately the last 10 years (2010-2021). Scientific databases, including Scopus, Web of Science, and PubMed, were searched using the following keywords either alone or in combination: cadmium, arsenic, lead, TQ, and oxidative stress. TQ, as a potent antioxidant, can distribute to cellular compartments and prevent oxidative damage of toxic metals. However, depending on the type of toxic metal and the carrier system used to release TQ in biological systems, its therapeutic dosage range may be varied.
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Affiliation(s)
- Farzad Ghasemi
- Faculty of Pharmacy, Eastern Mediterranean University, Famagusta, North Cyprus, Turkey
| | - Amir Nili-Ahmadabadi
- Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
- Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Navid Omidifar
- Medical Education Research Center, Department of Pathology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Nili-Ahmadabadi
- Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Gamit N, Patil M, B Sundrappa S, Sundaram SM, Sethi G, Dharmarajan A, Warrier S. Mesenchymal stem cell-derived rapid drug screening system for Alzheimer's disease for the identification of novel drugs. Drug Dev Res 2023; 84:1496-1512. [PMID: 37571798 DOI: 10.1002/ddr.22102] [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: 02/14/2023] [Revised: 06/11/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023]
Abstract
A reliable and efficient in vitro model is needed to screen drugs for Alzheimer's disease (AD), as many drugs are currently in the developmental stage. To address this, we developed an in vitro model using amniotic membrane-derived mesenchymal stem cells (AM-MSCs) to screen novel drugs for AD. We differentiated AM-MSCs into neurons and degenerated them using beta amyloid1-42 (Aß). We then tested AD drugs, which are commercially available such as donepezil, rivastigmine, memantine, citicoline, and two novel drugs, that is, probucol, an anti-hyperlipidaemic drug, and NMJ-2, a cinnamic acid analogue for their potential to protect the cells against neurodegeneration. We used gene expression and immunofluorescence staining to assess the neuroprotective ability of these drugs. We also measured the ability of these drugs to reduce lactate dehydrogenase, reactive oxygen species, and nitric oxide levels, as well as their ability to stabilize the mitochondrial membrane potential and increase acetylcholine (ACh) levels. The AD drugs and novel drugs reduced cytotoxicity and oxidative stress, stabilized mitochondrial membrane potential, and restored ACh levels. Furthermore, they reduced BACE1 expression, with a concomitant increase in the expression of cholinergic markers. This AM-MSCs-based AD-like model has immense potential to be an accurate human model and an alternative to animal models for testing a large number of lead compounds in a short time. Our results also suggest that the novel drugs probucol and NMJ-2 may protect against Aß-induced neurodegeneration.
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Affiliation(s)
- Naisarg Gamit
- Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education (MAHE), Bangalore, India
| | - Manasi Patil
- Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education (MAHE), Bangalore, India
| | - Soumya B Sundrappa
- Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education (MAHE), Bangalore, India
| | - S Mohana Sundaram
- Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education (MAHE), Bangalore, India
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Arun Dharmarajan
- Department of Biomedical Sciences, Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India
| | - Sudha Warrier
- Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education (MAHE), Bangalore, India
- Cuor Stem Cellutions Pvt Ltd, Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education (MAHE), Bangalore, India
- Department of Biotechnology, Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India
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Abo Mansour HE, Elberri AI, Ghoneim MES, Samman WA, Alhaddad AA, Abdallah MS, El-Berri EI, Salem MA, Mosalam EM. The Potential Neuroprotective Effect of Thymoquinone on Scopolamine-Induced In Vivo Alzheimer's Disease-like Condition: Mechanistic Insights. Molecules 2023; 28:6566. [PMID: 37764343 PMCID: PMC10534545 DOI: 10.3390/molecules28186566] [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: 07/20/2023] [Revised: 08/31/2023] [Accepted: 09/05/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Alzheimer's disease (AD) is a common neurodegenerative disorder without effective treatment. Thymoquinone (TQ) has demonstrated potential in exhibiting anti-inflammatory, anti-cancer, and antioxidant characteristics. Despite TQ's neuroprotection effect, there is a scarcity of information regarding its application in AD research, and its molecular trajectories remain ambiguous. Thus, the objective of the current investigation was to examine the potential beneficial effects and underlying mechanisms of TQ in scopolamine (SCOP)-induced neuronal injury to mimic AD in vivo model. METHODS Thirty mice were divided into normal, SCOP, and TQ groups. The Y-maze and pole climbing tests were performed to measure memory and motor performance. Afterwards, histopathological and immunohistochemical examinations were carried out. Furthermore, peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway-related proteins and genes were detected with an emphasis on the role of miR-9. RESULTS TQ has the potential to ameliorate cognitive deficits observed in SCOP-induced AD-like model, as evidenced by the improvement in behavioral outcomes, histopathological changes, modulation of the expression pattern of PPAR-γ downstream targets with a significant decrease in the deposition of amyloid beta (Aβ). CONCLUSIONS TQ provided meaningful multilevel neuroprotection through its anti-inflammatory and its PPAR-γ agonist activity. Consequently, TQ may possess a potential beneficial role against AD development.
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Affiliation(s)
- Hend E. Abo Mansour
- Biochemistry Department, Faculty of Pharmacy, Menoufia University, Shibin El-Kom 32511, Egypt;
| | - Aya Ibrahim Elberri
- Genetic Engineering and Molecular Biology Division, Department of Zoology, Faculty of Science, Menoufia University, Shibin El-Kom 32511, Egypt;
| | - Mai El-Sayed Ghoneim
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Sadat City (USC), Sadat City 32897, Egypt;
| | - Waad A. Samman
- Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Medina 42353, Saudi Arabia; (W.A.S.); (A.A.A.)
| | - Aisha A. Alhaddad
- Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Medina 42353, Saudi Arabia; (W.A.S.); (A.A.A.)
| | - Mahmoud S. Abdallah
- Clinical Pharmacy Department, Faculty of Pharmacy, University of Sadat City (USC), Sadat City 32897, Egypt;
| | - Eman I. El-Berri
- Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt;
| | - Mohamed A. Salem
- Department of Pharmacognosy, Faculty of Pharmacy, Menoufia University, Shibin El-Kom 32511, Egypt;
| | - Esraa M. Mosalam
- Biochemistry Department, Faculty of Pharmacy, Menoufia University, Shibin El-Kom 32511, Egypt;
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Barber K, Mendonca P, Evans JA, Soliman KFA. Antioxidant and Anti-Inflammatory Mechanisms of Cardamonin through Nrf2 Activation and NF-kB Suppression in LPS-Activated BV-2 Microglial Cells. Int J Mol Sci 2023; 24:10872. [PMID: 37446045 PMCID: PMC10341801 DOI: 10.3390/ijms241310872] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 06/23/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Chronic oxidative stress (OS) and inflammation are implicated in developing and progressing neurodegenerative diseases (NDs). The chronic activation of microglia cells leads to the overproduction of several substances, including nitric oxide and reactive oxygen species, which can induce neurodegeneration. Natural compounds have recently been investigated for their potential to protect cells from OS and to improve many disease-related conditions. Cardamonin (CD) is a bioactive compound in many plants, such as Alpinia katsumadai and Alpinia conchigera. The present study examined the effects of CD on LPS-activated BV-2 microglial cells. The cell viability results showed that the increasing concentrations of CD, ranging from 0.78 to 200 µM, induced BV-2 cell cytotoxicity in a dose-response manner. In the nitric oxide assay, CD concentrations of 6.25 to 25 µM reduced the release of nitric oxide in LPS-activated BV-2 cells by 90% compared to those treated with LPS only (p ≤ 0.0001). CD (6.25 µM) significantly decreased the cellular production of SOD (3-fold (p ≤ 0.05)) and increased the levels of expression of CAT (2.5-fold (p ≤ 0.05)) and GSH (2-fold (p ≤ 0.05)) in the LPS-activated BV-2 cells. Furthermore, on RT-PCR arrays, CD (6.25 µM) downregulated mRNA expression of CCL5/RANTES (5-fold), NOS2 (2-fold), SLC38A1 (3-fold), TXNIP (2-fold), SOD1 (2-fold), SOD2 (1.5-fold) and upregulated GSS (1.9-fold), GCLC (1.7-fold) and catalase (2.9-fold) expression, indicating CD efficacy in modulating genes involved in OS and inflammation. Furthermore, CD (6.25 µM) increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and lowered the levels of Kelch-like ECH-associated protein 1 (Keap1), indicating that this may be the signaling responsible for the elevation of antioxidant factors. Lastly, the results showed that CD (6.25 µM) modulated genes and proteins associated with the NF-kB signaling, downregulating genes related to excessive neuroinflammation. These results imply that CD may be a potential compound for developing therapeutic and preventive agents in treating neurodegeneration induced by excessive OS and inflammation.
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Affiliation(s)
- Kimberly Barber
- Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL 32307, USA; (K.B.); (J.A.E.)
| | - Patricia Mendonca
- Department of Biology, College of Science and Technology, Florida A&M University, Tallahassee, FL 32307, USA
| | - Jasmine A. Evans
- Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL 32307, USA; (K.B.); (J.A.E.)
| | - Karam F. A. Soliman
- Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL 32307, USA; (K.B.); (J.A.E.)
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AlDreini S, Fatfat Z, Abou Ibrahim N, Fatfat M, Gali-Muhtasib H, Khalife H. Thymoquinone enhances the antioxidant and anticancer activity of Lebanese propolis. World J Clin Oncol 2023; 14:203-214. [PMID: 37275937 PMCID: PMC10236984 DOI: 10.5306/wjco.v14.i5.203] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 03/24/2023] [Accepted: 04/12/2023] [Indexed: 05/19/2023] Open
Abstract
BACKGROUND Reactive oxygen species (ROS) are produced by multiple cellular processes and are maintained at optimal levels in normal cells by endogenous antioxidants. In recent years, the search for potential exogenous antioxidants from dietary sources has gained considerable attention to eliminate excess ROS that is associated with oxidative stress related diseases including cancer. Propolis, a resinous honeybee product, has been shown to have protective effects against oxidative stress and anticancer effects against several types of neoplasms. AIM To investigate the antioxidant and anticancer potential of Lebanese propolis when applied alone or in combination with the promising anticancer compound Thymoquinone (TQ) the main constituent of Nigella sativa essential oil. METHODS Crude extracts of Lebanese propolis collected from two locations, Rashaya and Akkar-Danniyeh, were prepared in methanol and the total phenolic content was determined by Folin-Ciocalteu method. The antioxidant activity was assessed by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and to inhibit H2O2-induced oxidative hemolysis of human erythrocytes. The anticancer activity was evaluated by [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide] MTT assay against HCT-116 human colorectal cancer cells and MDA-MB-231 human breast cancer cells. RESULTS The total phenolic content of propolis extract from Rashaya and Akkar-Danniyeh were 56.81 µg and 83.503 µg of gallic acid equivalent /mg of propolis, respectively. Both natural agents exhibited strong antioxidant activities as evidenced by their ability to scavenge DPPH free radical and to protect erythrocytes against H2O2-induced hemolysis. They also dose-dependently decreased the viability of both cancer cell lines. The IC50 value of each of propolis extract from Rashaya and Akkar-Danniyeh or TQ was 22.3, 61.7, 40.44 µg/mL for breast cancer cells at 72 h and 33.3, 50.9, 33.5 µg/mL for colorectal cancer cells at the same time point, respectively. Importantly, the inhibitory effects of propolis on DPPH radicals and cancer cell viability were achieved at half its concentration when combined with TQ. CONCLUSION Our results indicate that Lebanese propolis extract has antioxidant and anticancer potential and its combination with TQ could possibly prevent ROS- mediated diseases.
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Affiliation(s)
- Sima AlDreini
- Rammal Rammal Laboratory (ATAC Group), Faculty of Sciences I, Hadath 1003, Lebanon
| | - Zaynab Fatfat
- Department of Biology, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Najwa Abou Ibrahim
- Rammal Rammal Laboratory (ATAC Group), Faculty of Sciences I, Hadath 1003, Lebanon
| | - Maamoun Fatfat
- Department of Biology, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Hala Gali-Muhtasib
- Department of Biology, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Hala Khalife
- Rammal Rammal Laboratory (ATAC Group), Faculty of Sciences I, Hadath 1003, Lebanon
- Applied Biochemistry Laboratory, School of Pharmacy, Camerino University, Camerino 62032, Italy
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11
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Yuhainis Firus Khan A, Mohtar F, Rahman TA, Muid SA, Froemming GRA, Nawawi H. In vitro study of Nigella sativa and thymoquinone activity on endothelial activation and monocyte adhesion. J Appl Biomed 2023. [PMID: 37212154 DOI: 10.32725/jab.2023.006] [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] [Indexed: 05/23/2023] Open
Abstract
INTRODUCTION Thymoquinone (TQ) is one of the bioactive compounds in Nigella sativa (NS). Also known as black seeds/cumin, it has been postulated to possess anti-atherogenic properties. However, research on the effects of NS oil (NSO) and TQ on atherogenesis remain scarce. The aim of this study is to determine gene and protein expression of Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Endothelial-eukocyte adhesion molecule (E-selectin) in Human Coronary Artery Endothelial Cells (HCAECs). METHODS HCAECs were stimulated for 24 hours (h) with 200 µg/ml of Lipopolysaccharides (LPS) and different concentrations of NSO (55, 110, 220, 440 µg/ml) or TQ (4.5, 9.0, 18.0, 36.0 µm). The effects of NSO and TQ on gene and protein expressions were measured using multiplex gene assay and ELISA assay, respectively. Rose Bengal assay was used to analyse monocyte binding activity. RESULTS NSO and TQ significantly reduced ICAM-1 and VCAM-1 gene and protein expressions. TQ showed significant reduction activity of the biomarkers in dose dependent manner. HCAECs pre-treated with NSO and TQ for 24 h significantly lowered monocytes adherence compared to non-treated HCAECs. CONCLUSIONS NSO and TQ supplementation have anti-atherogenic properties and inhibit monocytes' adherence to HCAECs via down-regulation of ICAM-1 expression. NSO could potentially be incorporated in standard treatment regimens to prevent atherosclerosis and its related complications.
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Affiliation(s)
- Al'Aina Yuhainis Firus Khan
- Universiti Teknologi MARA, Institute for Pathology, Laboratory and Forensic Medicine (I-PPerForM), Sungai Buloh, Malaysia
| | - Fahmi Mohtar
- Universiti Teknologi MARA, Centre for Pathology Diagnostic and Research Laboratories (CPDRL), Sungai Buloh, Malaysia
| | - Thuhairah Abdul Rahman
- Universiti Teknologi MARA, Institute for Pathology, Laboratory and Forensic Medicine (I-PPerForM), Sungai Buloh, Malaysia
- Universiti Teknologi MARA, Faculty of Medicine, Department of Pathology, Sungai Buloh, Malaysia
- Universiti Teknologi MARA, Integrative Pharmacogenomics Institute (iPROMISE), Puncak Alam, Malaysia
| | - Suhaila Abdul Muid
- Universiti Teknologi MARA, Institute for Pathology, Laboratory and Forensic Medicine (I-PPerForM), Sungai Buloh, Malaysia
- Universiti Teknologi MARA, Faculty of Medicine, Department of Biochemistry and Molecular Medicine, Sungai Buloh, Malaysia
| | - Gabriele Ruth Anisah Froemming
- Universiti Teknologi MARA, Institute for Pathology, Laboratory and Forensic Medicine (I-PPerForM), Sungai Buloh, Malaysia
- Universiti Malaysia Sarawak, Faculty of Medicine and Health Sciences, Department of Basic Medical Sciences, Kota Samarahan, Malaysia
| | - Hapizah Nawawi
- Universiti Teknologi MARA, Institute for Pathology, Laboratory and Forensic Medicine (I-PPerForM), Sungai Buloh, Malaysia
- Universiti Teknologi MARA, Faculty of Medicine, Department of Pathology, Sungai Buloh, Malaysia
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Gawas CG, Mathur S, Wani M, Tabassum H. Nigella sativa and its nano-mediated approach toward management of neurodegenerative disorders: A review. IBRAIN 2023; 9:111-123. [PMID: 37786518 PMCID: PMC10529340 DOI: 10.1002/ibra.12091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/16/2023] [Accepted: 01/19/2023] [Indexed: 10/04/2023]
Abstract
Nigella sativa L., also known as black seed or black cumin, is a plant that has been used for centuries. In the past, this flowering plant was used as a food preservative and medicinal herb. A vital component of Nigella sativa, thymoquinone (TQ), plays a significant therapeutic role in the management of most diseases, including cancer, diabetes mellitus, hypertension, inflammation, gastrointestinal disorders, and neurodegenerative disorders. Neurodegenerative disorders are primarily caused by neurotransmitter hypoactivity, particularly insufficient serotonin activity. It has been discovered that many medicinal herbs and their active compounds have therapeutic value. Black cumin seeds have been used to heal ailments and its history traces back to ancient times such as ancient Babylonia. They can be used applied to alleviate edema, hair loss, and bruising, and consumd to treat stomach issues. It is one of the most feasible and effective medicinal plants. The use of nanoformulations based on Nigella sativa and TQ to treat neurodegenerative diseases (NDs) has yielded promising outcomes. Customized administration of nanoparticle (NP) systems and nanomedicine are two of the many options for drug delivery to the central nervous system (CNS) that are attracting increasing interest. Delivering a therapeutic and diagnostic substance to a particular location is the core target of NPs. Because of their distinct cell uptake and trafficking mechanisms, NPs can reduce the amount that accumulates in undesirable organs. The focus of the current review is on recent studies on the various neuroprotective properties of Nigella sativa as well as nanoformulations for NDs and the brain's uptake of NPs. The review summarizes the In vivo, In vitro, and In silico studies on the protective effects of black cumin against neurodegenerative disorders.
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Affiliation(s)
- Chaitali G. Gawas
- Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil VidyapeethPuneMaharashtraIndia
| | - Sakshi Mathur
- Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil VidyapeethPuneMaharashtraIndia
| | - Minal Wani
- Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil VidyapeethPuneMaharashtraIndia
| | - Heena Tabassum
- Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil VidyapeethPuneMaharashtraIndia
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Adinew GM, Messeha SS, Taka E, Badisa RB, Soliman KFA. Anticancer Effects of Thymoquinone through the Antioxidant Activity, Upregulation of Nrf2, and Downregulation of PD-L1 in Triple-Negative Breast Cancer Cells. Nutrients 2022; 14:nu14224787. [PMID: 36432484 PMCID: PMC9695946 DOI: 10.3390/nu14224787] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 11/04/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022] Open
Abstract
The variety of therapies available for treating and preventing triple-negative breast cancer (TNBC) is constrained by the absence of progesterone receptors, estrogen receptors, and human epidermal growth factor receptor 2. Nrf2 (nuclear factor-erythroid 2-related factor), and PD-L1 (program cell death ligand 1), a downstream signaling target, have a strong correlation to oxidative stress and inflammation, major factors in the development and progression of TNBC. In this study, the genetically distinct MDA-MB-231 and MDA-MB-468 TNBC cells were treated with the natural component thymoquinone (TQ). The results show that TQ exhibits considerable antioxidant activity and decreases the generation of H2O2, at the same time increasing catalase (CAT) activity, superoxide dismutase (SOD) enzyme, and glutathione (GSH). Additionally, the results show that TQ treatment increased the levels of the different genes involved in the oxidative stress-antioxidant defense system PRNP, NQO1, and GCLM in both cell lines with significant large-fold change in MDA-MB-468 cells (+157.65 vs. +1.7, +48.87 vs. +2.63 and +4.78 vs. +2.17), respectively. Nrf2 mRNA and protein expression were also significantly increased in TQ-treated TNBC cells despite being higher in MDA-MB-468 cells (6.67 vs. 4.06). Meanwhile, TQ administration increased mRNA levels while decreasing PD-L1 protein expression in both cell lines. In conclusion, TQ modifies the expression of multiple oxidative-stress-antioxidant system genes, ROS, antioxidant enzymes, Nrf2, and PD-L1 protein, pointing to the therapeutic potential and chemopreventive utilization of TQ in TNBC.
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Thymoquinone Improved Nonylphenol-Induced Memory Deficit and Neurotoxicity Through Its Antioxidant and Neuroprotective Effects. Mol Neurobiol 2022; 59:3600-3616. [PMID: 35355194 DOI: 10.1007/s12035-022-02807-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Accepted: 03/17/2022] [Indexed: 12/27/2022]
Abstract
Nonylphenol (NP), a well-known endocrine-disrupter chemical, has several harmful effects on the central nervous system including neuroendocrine disruption, cognitive impairment, and neurotoxicity. Thymoquinone (TQ) is a main bioactive compound in the black seeds of Nigella sativa that has antioxidant, anti-inflammatory, and neuroprotective properties. Here, we investigated the neuroprotective effect of TQ against NP-induced memory deficit and neurotoxicity in rats. To induce memory impairment, NP (25 mg/kg) was used as gavage in male Wistar rats for 21 days. TQ (2.5, 5, and 10 mg/kg) was intraperitoneally administered in NP-treated animals. The morris water maze test was performed to assess spatial learning and memory. The hippocampal tissues were isolated from the brain for histopathological evaluation. Biochemical, molecular, and cellular tests were performed to quantify oxidant (malondialdehyde; MDA)/antioxidant (superoxide dismutase (SOD), total antioxidant capacity (TAC), and reduced glutathione (GSH) parameters) as well as markers for astrocytic activation (glial fibrillary acidic protein; GFAP) and neuronal death (alpha-synuclein; α-syn). Results showed TQ (5 mg/kg) significantly improved NP-induced memory impairment. Histological data revealed a significant increase in the number of necrotic cells in hippocampus, and TQ treatment markedly decreased this effect. The GSH and TAC levels were significantly increased in TQ-treated groups compared to NP group. The molecular analysis indicated that NP increased GFAP and decreased α-syn expression and TQ treatment did the reverse. In vitro study in astrocytes isolated from mice brain showed that TQ significantly increased cell viability in NP-induced cytotoxicity. This study strongly indicates that TQ has neuroprotective effects on NP-induced neurotoxicity through reducing oxidative damages and neuroinflammation. This study investigates the behavioral neurotoxicity induced by Nonylphenol (NP) and the protective effects of Thymoquinone (TQ) as a potent antioxidant compound using molecular, cell culture, histopathological and biochemical techniques.
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Chen M, Liang J, Wang Y, Liu Y, Zhou C, Hong P, Zhang Y, Qian ZJ. A new benzaldehyde from the coral-derived fungus Aspergillus terreus C23-3 and its anti-inflammatory effects via suppression of MAPK signaling pathway in RAW264.7 cells. J Zhejiang Univ Sci B 2022; 23:230-240. [PMID: 35261218 DOI: 10.1631/jzus.b2100807] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Marine fungi are important members of the marine microbiome, which have been paid growing attention by scientists in recent years. The secondary metabolites of marine fungi have been reported to contain rich and diverse compounds with novel structures (Chen et al., 2019). Aspergillus terreus, the higher level marine fungus of the Aspergillus genus (family of Trichocomaceae, order of Eurotiales, class of Eurotiomycetes, phylum of Ascomycota), is widely distributed in both sea and land. In our previous study, the coral-derived A. terreus strain C23-3 exhibited potential in producing other biologically active (with antioxidant, acetylcholinesterase inhibition, and anti-inflammatory activity) compounds like arylbutyrolactones, territrems, and isoflavones, and high sensitivity to the chemical regulation of secondary metabolism (Yang et al., 2019, 2020; Nie et al., 2020; Ma et al., 2021). Moreover, we have isolated two different benzaldehydes, including a benzaldehyde with a novel structure, from A. terreus C23-3 which was derived from Pectinia paeonia of Xuwen, Zhanjiang City, Guangdong Province, China.
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Affiliation(s)
- Minqi Chen
- College of Food Science and Technology, School of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China.,Shenzhen Institute of Guangdong Ocean University, Guangdong Ocean University, Shenzhen 518108, China
| | - Jinyue Liang
- College of Food Science and Technology, School of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China
| | - Yuan Wang
- College of Food Science and Technology, School of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China
| | - Yayue Liu
- College of Food Science and Technology, School of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China.,Shenzhen Institute of Guangdong Ocean University, Guangdong Ocean University, Shenzhen 518108, China.,Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang 524025, China.,Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China
| | - Chunxia Zhou
- College of Food Science and Technology, School of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China.,Shenzhen Institute of Guangdong Ocean University, Guangdong Ocean University, Shenzhen 518108, China.,Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang 524025, China.,Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China
| | - Pengzhi Hong
- College of Food Science and Technology, School of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China.,Shenzhen Institute of Guangdong Ocean University, Guangdong Ocean University, Shenzhen 518108, China.,Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang 524025, China.,Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China
| | - Yi Zhang
- College of Food Science and Technology, School of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China. .,Shenzhen Institute of Guangdong Ocean University, Guangdong Ocean University, Shenzhen 518108, China. .,Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang 524025, China. .,Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China.
| | - Zhong-Ji Qian
- College of Food Science and Technology, School of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China. , .,Shenzhen Institute of Guangdong Ocean University, Guangdong Ocean University, Shenzhen 518108, China. , .,Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang 524025, China. ,
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Mahmud NM, Paraoan L, Khaliddin N, Kamalden TA. Thymoquinone in Ocular Neurodegeneration: Modulation of Pathological Mechanisms via Multiple Pathways. Front Cell Neurosci 2022; 16:786926. [PMID: 35308121 PMCID: PMC8924063 DOI: 10.3389/fncel.2022.786926] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 02/09/2022] [Indexed: 02/01/2023] Open
Abstract
Thymoquinone is a naturally occurring compound and is the major component of Nigella sativa, also known as black seed or black cumin. For centuries thymoquinone has been used especially in the Middle East traditionally to treat wounds, asthma, allergies, fever, headache, cough, hypertension, and diabetes. Studies have suggested beneficial effects of thymoquinone to be attributed to its antioxidant, antibacterial, anti-oxidative stress, anti-inflammatory, and neuroprotective properties. Recently, there has been a surge of interest in thymoquinone as a treatment for neurodegeneration in the brain, such as that seen in Alzheimer’s (AD) and Parkinson’s diseases (PD). In vitro and in vivo studies on animal models of AD and PD suggest the main neuroprotective mechanisms are based on the anti-inflammatory and anti-oxidative properties of thymoquinone. Neurodegenerative conditions of the eye, such as Age-related Macular Degeneration (AMD) and glaucoma share at least in part similar mechanisms of neuronal cell death with those occurring in AD and PD. This review aims to summarize and critically analyze the evidence to date of the effects and potential neuroprotective actions of thymoquinone in the eye and ocular neurodegenerations.
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Affiliation(s)
- Nur Musfirah Mahmud
- UM Eye Research Centre, Department of Ophthalmology, University of Malaya, Kuala Lumpur, Malaysia
- Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Luminita Paraoan
- Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Nurliza Khaliddin
- UM Eye Research Centre, Department of Ophthalmology, University of Malaya, Kuala Lumpur, Malaysia
| | - Tengku Ain Kamalden
- UM Eye Research Centre, Department of Ophthalmology, University of Malaya, Kuala Lumpur, Malaysia
- *Correspondence: Tengku Ain Kamalden,
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Tiji S, Lakrat M, Rokni Y, Mejdoubi EM, Hano C, Addi M, Asehraou A, Mimouni M. Characterization and Antimicrobial Activity of Nigella sativa Extracts Encapsulated in Hydroxyapatite Sodium Silicate Glass Composite. Antibiotics (Basel) 2022; 11:170. [PMID: 35203773 PMCID: PMC8868394 DOI: 10.3390/antibiotics11020170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/22/2022] [Accepted: 01/25/2022] [Indexed: 12/10/2022] Open
Abstract
N. sativa is an interesting source of bioactive compounds commonly used for various therapeutic purposes. Associate its seeds extracts with biomaterials to improve their antimicrobial properties are highly demanded. This study aims to investigate the encapsulation of NS extracts in hydroxyapatite nanoparticle sodium silicate glass (nHap/SSG) scaffold. NS essential oil (HS) was extracted by hydrodistillation, while hexane (FH) and acetone extracts (FA) were obtained using Soxhlet extraction. (FH) was the most abundant (34%) followed by (FA) (2.02%) and (HS) (1.2%). GC-MS chromatography showed that the (HS) contained beta cymene, alpha thujene, β-pinene and thymoquinone, while (FH) had mostly fatty acids and (FA) decane, 2.9-dimethyl, benzene 1,3,3-trimethylnonyl and beta cymene. Loaded nHap/SGG scaffolds with various amount of (FH), (HS) and (FA) at 1.5, 3, and 6 wt%; were elaborated then characterized by ATR-FTIR, X-ray and SEM techniques and their antimicrobial activity was studied. Samples loaded with 1.5 wt% HE was highly active against C. albicans (19 mm), and at 3 wt% on M. luteus (20 mm) and S. aureus (20 mm). Additionally, loaded scaffolds with 1.5 wt% AE had an important activity against M. luteus (18.9 mm) and S. aureus (19 mm), while the EO had low activities on all bacterial strains. The outcome of this finding indicated that loaded scaffolds demonstrated an important antimicrobial effect that make them promising materials for a wide range of medical applications.
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Affiliation(s)
- Salima Tiji
- Applied Chemistry and Environment Laboratory, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco;
| | - Mohammed Lakrat
- Solid Mineral Chemistry Laboratory, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco; (M.L.); (E.M.M.)
- High Institute of Biological and Paramedical Sciences, ISSB-P, Mohammed VI Polytechnic University (UM6P), Benguerir 43150, Morocco
| | - Yahya Rokni
- Bio-Resources, Biotechnology, Ethno-Pharmacology and Health Laboratory, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco; (Y.R.); (A.A.)
- Research Unit Bioprocess and Biointerfaces, Laboratory of Industrial Engineering and Surface Engineering, National School of Applied Sciences, Sultan Moulay Slimane University, 17 Mghila, Beni Mellal 23000, Morocco
| | - El Miloud Mejdoubi
- Solid Mineral Chemistry Laboratory, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco; (M.L.); (E.M.M.)
| | - Christophe Hano
- Laboratoire de Biologie des Ligneux et des Grandes Cultures, INRA USC1328, Orleans University, CEDEX 2, 45067 Orléans, France
| | - Mohamed Addi
- Laboratoire d’Amélioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Faculté des Sciences, Université Mohammed Premier, Oujda 60000, Morocco;
| | - Abdeslam Asehraou
- Bio-Resources, Biotechnology, Ethno-Pharmacology and Health Laboratory, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco; (Y.R.); (A.A.)
| | - Mostafa Mimouni
- Applied Chemistry and Environment Laboratory, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco;
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Chaturvedi S, Gupta R, Gupta N, Ansari N, Ghazi N, Naseem A, Chaudhry RK, Ansari UA, Khan A, Jahan S. Nigella sativa and its chemical constituents: A promising approach against neurodegenerative disorders. BLACK SEEDS (NIGELLA SATIVA) 2022:149-176. [DOI: 10.1016/b978-0-12-824462-3.00013-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Lunić TM, Mandić MR, Oalđe Pavlović MM, Sabovljević AD, Sabovljević MS, Božić Nedeljković BĐ, Božić BĐ. The Influence of Seasonality on Secondary Metabolite Profiles and Neuroprotective Activities of Moss Hypnum cupressiforme Extracts: In Vitro and In Silico Study. PLANTS (BASEL, SWITZERLAND) 2022; 11:plants11010123. [PMID: 35009126 PMCID: PMC8747716 DOI: 10.3390/plants11010123] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 12/28/2021] [Accepted: 12/29/2021] [Indexed: 05/14/2023]
Abstract
Numerous representatives of mosses, including Hypnum cupressiforme, have been used to alleviate different inflammation-related conditions. However, the mode of action underlying this anti-inflammatory potential has been poorly understood. Moreover, the influence of seasonality on the chemical composition and biological activity of mosses is generally overlooked. This study aimed to investigate the influence of seasonal changes (spring, summer, and autumn) on secondary metabolite composition and biological activities of ethyl acetate H. cupressiforme extracts. Antioxidant activity was measured using β-carotene bleaching assay, while MTT, NBT, ELISA, and Griess assays were carried out to explore the anti-neuroinflammatory and neuroprotective potential of extracts. Inhibitory activities on acetylcholinesterase and tyrosinase were assessed experimentally and by docking analysis. The highest content of secondary metabolites and antioxidant activity were observed in moss during the summer. Extracts inhibited the secretion of ROS, NO, TNF-α, and IL-6, alleviating the inflammatory potential of H2O2 and LPS in microglial and neuronal cells. Strong inhibitory effects on acetylcholinesterase and tyrosinase were observed in vitro. Docking analyses revealed high-affinity interactions of secondary metabolites present in H. cupressiforme with important enzyme residues. Altogether, these results reveal the neuroprotective potential and the significance of seasonal fluctuations on secondary metabolite content and biological activities in moss H. cupressiforme.
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Affiliation(s)
- Tanja M. Lunić
- Institute of Physiology and Biochemistry “Ivan Đaja”, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (T.M.L.); (M.R.M.)
| | - Marija R. Mandić
- Institute of Physiology and Biochemistry “Ivan Đaja”, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (T.M.L.); (M.R.M.)
| | - Mariana M. Oalđe Pavlović
- Institute of Botany and Botanical Garden “Jevremovac”, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (M.M.O.P.); (A.D.S.); (M.S.S.)
| | - Aneta D. Sabovljević
- Institute of Botany and Botanical Garden “Jevremovac”, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (M.M.O.P.); (A.D.S.); (M.S.S.)
| | - Marko S. Sabovljević
- Institute of Botany and Botanical Garden “Jevremovac”, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (M.M.O.P.); (A.D.S.); (M.S.S.)
- Department of Botany, Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University in Kosice, Mánesova 23, 040 01 Kosice, Slovakia
| | - Biljana Đ. Božić Nedeljković
- Institute of Physiology and Biochemistry “Ivan Đaja”, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (T.M.L.); (M.R.M.)
- Correspondence: (B.Đ.B.N.); (B.Đ.B.); Tel.: +381-11-303-23-56 (B.Đ.B.N.)
| | - Bojan Đ. Božić
- Institute of Physiology and Biochemistry “Ivan Đaja”, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (T.M.L.); (M.R.M.)
- Correspondence: (B.Đ.B.N.); (B.Đ.B.); Tel.: +381-11-303-23-56 (B.Đ.B.N.)
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Pei Y, Yang S, Xiao Z, Zhou C, Hong P, Qian ZJ. Structural Characterization of Sulfated Polysaccharide Isolated From Red Algae ( Gelidium crinale) and Antioxidant and Anti-Inflammatory Effects in Macrophage Cells. Front Bioeng Biotechnol 2021; 9:794818. [PMID: 34869300 PMCID: PMC8637441 DOI: 10.3389/fbioe.2021.794818] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 10/20/2021] [Indexed: 12/18/2022] Open
Abstract
Gelidium crinale, the red algae belonging to Geliaceae Gelidium, is a traditional edible and industrial alga in China. A sulfated polysaccharide (GNP) is successfully separated from Gelidium crinale by acid extraction and two-step column chromatography. Chemical analysis showed that the molecular weight of GNP was 25.8 kDa and the monosaccharide composition had the highest galactose content and confirmed the presence and content (16.5%) of sulfate by Fourier transform infrared spectroscopy (FT-IR) spectrometry as well as barium chloride-gelatin methods. In addition, the effect of GNP on lipopolysaccharide (LPS)-induced oxidative stress and inflammation in macrophages was also evaluated. The research results showed that GNP had fairly strong scavenging activities on 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical, hydroxyl radical, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and had Fe2+-chelating ability in a dose-dependent manner. At the same time, it significantly inhibits the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and the production of pro-inflammatory cytokines in RAW 264.7 cells induced by LPS through blocking the mitogen-activated protein kinase (MAPK)/nuclear factor kappa beta (NF-κB) signaling pathway. These results indicate that GNP may be a latent component anti-inflammation in pharmaceutical and functional food industries.
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Affiliation(s)
- Yu Pei
- College of Food Science and Technology, School of Chemistry and Environment, Shenzhen Institute of Guangdong Ocean University, Zhanjiang, China.,Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang, China
| | - Shengtao Yang
- College of Food Science and Technology, School of Chemistry and Environment, Shenzhen Institute of Guangdong Ocean University, Zhanjiang, China.,Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang, China
| | - Zhenbang Xiao
- College of Food Science and Technology, School of Chemistry and Environment, Shenzhen Institute of Guangdong Ocean University, Zhanjiang, China.,Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang, China
| | - Chunxia Zhou
- College of Food Science and Technology, School of Chemistry and Environment, Shenzhen Institute of Guangdong Ocean University, Zhanjiang, China.,Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang, China
| | - Pengzhi Hong
- College of Food Science and Technology, School of Chemistry and Environment, Shenzhen Institute of Guangdong Ocean University, Zhanjiang, China.,Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang, China
| | - Zhong-Ji Qian
- College of Food Science and Technology, School of Chemistry and Environment, Shenzhen Institute of Guangdong Ocean University, Zhanjiang, China.,Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang, China
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21
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Chemical Composition Related to Antimicrobial Activity of Moroccan Nigella sativa L. Extracts and Isolated Fractions. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:8308050. [PMID: 34725555 PMCID: PMC8557078 DOI: 10.1155/2021/8308050] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 10/07/2021] [Indexed: 11/23/2022]
Abstract
Background Nigella sativa L. (NS) is an aromatic and medicinal plant commonly used in Mediterranean cuisine. Its grains contain a large amount of fixed oil and have many therapeutic virtues and medicinal properties (antioxidant, antidiabetic, antimicrobial, and anticancer). Aim The aim of this work is to study the antimicrobial activity of Nigella sativa L. extracts and separated fractions on various pathogenic strains and to correlate that with its chemical composition. Methods Extracts from Moroccan Nigella sativa seeds were extracted using successive organic solvents, and their hexane and acetone extracts were separated by column chromatography. The chemical composition of extracts, fractions, and essential oil was determined by GC-MS and HPLC-DAD. Extracts and fractions were evaluated for antimicrobial activity through disk diffusion against Gram-positive bacteria (Staphylococcus aureus, Bacillus cereus, and Listeria innocua), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and yeast (Candida pelliculosa) for 1 mg/mL concentration. Bacterial strains were followed to study their behaviors over time in different concentrations. The minimum inhibitory concentration of Nigella sativa essential oil was determined against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Candida albicans. Results and Conclusion. Although hexane extract was active against both types of bacteria (Gram+ and Gram−), some of its fractions were specifically active against only one type. Fraction (SH4) had the highest activity (15 mm inhibitory diameter). Acetone extract was nonactive but surprisingly resulted in specific active fractions, and the most interesting one was (SA7) that had an inhibitory diameter of 13 mm. This antibacterial effect was related to fatty acids (linoleic and palmitic acids) in (SH4) and 17 pentatriacontene in (SA7). Moreover, the antifungal activity of hexane fractions (10–13 mm) was higher than hexane extract (8 mm), but for acetone, it was the opposite. Acetone extract had a higher activity (18 mm) than its fractions (8–12 mm), except for (SA7) (19 mm). Those inhibitions were attributed to gallic acid, cysteine, and apigenin in acetone extract and cysteine with ascorbic acid in fraction (SA7). Antifungal activity of the essential oil was more pronounced than the antibacterial one. Indeed, determined MICs in the first case were on the microgram scale (MIC = 8 μg/mL, Candida albicans), while in the second case, they were on the milligram scale (MIC = 0.96 mg/mL for Staphylococcus aureus, 0.5 mg/mL for Bacillus cereus, and 0.68 mg/mL for Escherichia coli). This antifungal activity was attributed to three major compounds beta-cymene, alpha-thujene, origanene, and thymoquinone. Results of strains behavior over time at different concentrations of the fractions showed all the curves went through a maximum around 20 hours and had a delay of expression of 5 hours at the start. Taking all results into count, Nigella sativa L. extracts and/or derived principles could form promising antimicrobial agents for therapeutical and industrial uses.
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Franzoni F, Scarfò G, Guidotti S, Fusi J, Asomov M, Pruneti C. Oxidative Stress and Cognitive Decline: The Neuroprotective Role of Natural Antioxidants. Front Neurosci 2021; 15:729757. [PMID: 34720860 PMCID: PMC8548611 DOI: 10.3389/fnins.2021.729757] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 09/09/2021] [Indexed: 12/14/2022] Open
Abstract
Free- radicals (Oxygen and Nitrogen species) are formed in mitochondria during the oxidative phosphorylation. Their high reactivity, due to not-engaged electrons, leads to an increase of the oxidative stress. This condition affects above all the brain, that usually needs a large oxygen amount and in which there is the major possibility to accumulate "Reacting Species." Antioxidant molecules are fundamental in limiting free-radical damage, in particular in the central nervous system: the oxidative stress, in fact, seems to worsen the course of neurodegenerative diseases. The aim of this review is to sum up natural antioxidant molecules with the greatest neuroprotective properties against free radical genesis, understanding their relationship with the Central Nervous System.
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Affiliation(s)
- Ferdinando Franzoni
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Giorgia Scarfò
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Sara Guidotti
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Jonathan Fusi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Muzaffar Asomov
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Carlo Pruneti
- Department of Medicine and Surgery, University of Parma, Parma, Italy
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23
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Hannan MA, Zahan MS, Sarker PP, Moni A, Ha H, Uddin MJ. Protective Effects of Black Cumin ( Nigella sativa) and Its Bioactive Constituent, Thymoquinone against Kidney Injury: An Aspect on Pharmacological Insights. Int J Mol Sci 2021; 22:ijms22169078. [PMID: 34445781 PMCID: PMC8396533 DOI: 10.3390/ijms22169078] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 08/21/2021] [Accepted: 08/22/2021] [Indexed: 02/07/2023] Open
Abstract
The prevalence of chronic kidney disease (CKD) is increasing worldwide, and a close association between acute kidney injury (AKI) and CKD has recently been identified. Black cumin (Nigella sativa) has been shown to be effective in treating various kidney diseases. Accumulating evidence shows that black cumin and its vital compound, thymoquinone (TQ), can protect against kidney injury caused by various xenobiotics, namely chemotherapeutic agents, heavy metals, pesticides, and other environmental chemicals. Black cumin can also protect the kidneys from ischemic shock. The mechanisms underlying the kidney protective potential of black cumin and TQ include antioxidation, anti-inflammation, anti-apoptosis, and antifibrosis which are manifested in their regulatory role in the antioxidant defense system, NF-κB signaling, caspase pathways, and TGF-β signaling. In clinical trials, black seed oil was shown to normalize blood and urine parameters and improve disease outcomes in advanced CKD patients. While black cumin and its products have shown promising kidney protective effects, information on nanoparticle-guided targeted delivery into kidney is still lacking. Moreover, the clinical evidence on this natural product is not sufficient to recommend it to CKD patients. This review provides insightful information on the pharmacological benefits of black cumin and TQ against kidney damage.
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Affiliation(s)
- Md. Abdul Hannan
- ABEx Bio-Research Center, East Azampur, Dhaka 1230, Bangladesh; (M.A.H.); (M.S.Z.); (P.P.S.); (A.M.)
- Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh
| | - Md. Sarwar Zahan
- ABEx Bio-Research Center, East Azampur, Dhaka 1230, Bangladesh; (M.A.H.); (M.S.Z.); (P.P.S.); (A.M.)
| | - Partha Protim Sarker
- ABEx Bio-Research Center, East Azampur, Dhaka 1230, Bangladesh; (M.A.H.); (M.S.Z.); (P.P.S.); (A.M.)
| | - Akhi Moni
- ABEx Bio-Research Center, East Azampur, Dhaka 1230, Bangladesh; (M.A.H.); (M.S.Z.); (P.P.S.); (A.M.)
| | - Hunjoo Ha
- Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea;
| | - Md Jamal Uddin
- ABEx Bio-Research Center, East Azampur, Dhaka 1230, Bangladesh; (M.A.H.); (M.S.Z.); (P.P.S.); (A.M.)
- Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea;
- Correspondence: ; Tel.: +82-2-3277-4075; Fax: +82-2-3277-2851
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Rather MA, Khan A, Alshahrani S, Rashid H, Qadri M, Rashid S, Alsaffar RM, Kamal MA, Rehman MU. Inflammation and Alzheimer's Disease: Mechanisms and Therapeutic Implications by Natural Products. Mediators Inflamm 2021; 2021:9982954. [PMID: 34381308 PMCID: PMC8352708 DOI: 10.1155/2021/9982954] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 05/24/2021] [Accepted: 07/10/2021] [Indexed: 02/08/2023] Open
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder with no clear causative event making the disease difficult to diagnose and treat. The pathological hallmarks of AD include amyloid plaques, neurofibrillary tangles, and widespread neuronal loss. Amyloid-beta has been extensively studied and targeted to develop an effective disease-modifying therapy, but the success rate in clinical practice is minimal. Recently, neuroinflammation has been focused on as the event in AD progression to be targeted for therapies. Various mechanistic pathways including cytokines and chemokines, complement system, oxidative stress, and cyclooxygenase pathways are linked to neuroinflammation in the AD brain. Many cells including microglia, astrocytes, and oligodendrocytes work together to protect the brain from injury. This review is focused to better understand the AD inflammatory and immunoregulatory processes to develop novel anti-inflammatory drugs to slow down the progression of AD.
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Affiliation(s)
- Mashoque Ahmad Rather
- Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar, Tamil Nadu 608002, India
| | - Andleeb Khan
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia
| | - Saeed Alshahrani
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia
| | - Hina Rashid
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia
| | - Marwa Qadri
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia
| | - Summya Rashid
- Department of Pharmacology & Toxicology, College of Pharmacy Girls Section, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia
| | - Rana M. Alsaffar
- Department of Pharmacology & Toxicology, College of Pharmacy Girls Section, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia
| | - Mohammad Amjad Kamal
- King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia
- West China School of Nursing/Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
- Enzymoics, 7 Peterlee Place, Hebersham, NSW 2770; Novel Global Community Educational Foundation, Australia
| | - Muneeb U. Rehman
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
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Malik S, Singh A, Negi P, Kapoor VK. Thymoquinone: A small molecule from nature with high therapeutic potential. Drug Discov Today 2021; 26:2716-2725. [PMID: 34303824 DOI: 10.1016/j.drudis.2021.07.013] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 05/23/2021] [Accepted: 07/17/2021] [Indexed: 12/14/2022]
Abstract
Thymoquinone (TQ; 2-isopropyl-5-methylbenzo-1, 4-quinone), the main active constituent of Nigella sativa, has been proven to have great therapeutic properties in numerous in vivo and in vitro models. Nevertheless, this molecule is not yet in clinical trials, largely because of its poor bioavailability and hydrophobicity. This review examines the different activities of TQ, as well as various combination therapies, nanotechnologies and clinical trials involving TQ. The TQ nanoparticle formulation shows better bioavailability than free TQ, and it is time for clinical trials of these formulations to realize the potential of TQ as a therapeutic.
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Affiliation(s)
- Safiya Malik
- School of Pharmaceutical Sciences, Shoolini University, Solan 173212, India
| | - Amardeep Singh
- School of Pharmaceutical Sciences, Shoolini University, Solan 173212, India
| | - Poonam Negi
- School of Pharmaceutical Sciences, Shoolini University, Solan 173212, India
| | - Vijay Kumar Kapoor
- School of Pharmaceutical Sciences, Shoolini University, Solan 173212, India.
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26
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Hannan MA, Rahman MA, Sohag AAM, Uddin MJ, Dash R, Sikder MH, Rahman MS, Timalsina B, Munni YA, Sarker PP, Alam M, Mohibbullah M, Haque MN, Jahan I, Hossain MT, Afrin T, Rahman MM, Tahjib-Ul-Arif M, Mitra S, Oktaviani DF, Khan MK, Choi HJ, Moon IS, Kim B. Black Cumin ( Nigella sativa L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety. Nutrients 2021; 13:1784. [PMID: 34073784 PMCID: PMC8225153 DOI: 10.3390/nu13061784] [Citation(s) in RCA: 111] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 05/20/2021] [Accepted: 05/21/2021] [Indexed: 02/07/2023] Open
Abstract
Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin (Nigella sativa L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific community, and pharmaceutical industries. The pleiotropic pharmacological effects of black cumin, and its main bioactive component thymoquinone (TQ), have been manifested by their ability to attenuate oxidative stress and inflammation, and to promote immunity, cell survival, and energy metabolism, which underlie diverse health benefits, including protection against metabolic, cardiovascular, digestive, hepatic, renal, respiratory, reproductive, and neurological disorders, cancer, and so on. Furthermore, black cumin acts as an antidote, mitigating various toxicities and drug-induced side effects. Despite significant advances in pharmacological benefits, this miracle herb and its active components are still far from their clinical application. This review begins with highlighting the research trends in black cumin and revisiting phytochemical profiles. Subsequently, pharmacological attributes and health benefits of black cumin and TQ are critically reviewed. We overview molecular pharmacology to gain insight into the underlying mechanism of health benefits. Issues related to pharmacokinetic herb-drug interactions, drug delivery, and safety are also addressed. Identifying knowledge gaps, our current effort will direct future research to advance potential applications of black cumin and TQ in health and diseases.
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Affiliation(s)
- Md. Abdul Hannan
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea; (M.A.H.); (R.D.); (B.T.); (Y.A.M.); (M.A.); (S.M.); (D.F.O.); (H.J.C.)
- Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh; (A.A.M.S.); (M.T.H.); (M.T.-U.-A.)
| | - Md. Ataur Rahman
- 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
| | - Abdullah Al Mamun Sohag
- Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh; (A.A.M.S.); (M.T.H.); (M.T.-U.-A.)
| | - Md. Jamal Uddin
- ABEx Bio-Research Center, East Azampur, Dhaka 1230, Bangladesh; (M.J.U.); (P.P.S.)
- Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Korea
| | - Raju Dash
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea; (M.A.H.); (R.D.); (B.T.); (Y.A.M.); (M.A.); (S.M.); (D.F.O.); (H.J.C.)
| | - Mahmudul Hasan Sikder
- Department of Pharmacology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh;
| | - Md. Saidur Rahman
- Department of Animal Science & Technology and BET Research Institute, Chung-Ang University, Gyeonggi-do, Anseong 17546, Korea;
| | - Binod Timalsina
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea; (M.A.H.); (R.D.); (B.T.); (Y.A.M.); (M.A.); (S.M.); (D.F.O.); (H.J.C.)
| | - Yeasmin Akter Munni
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea; (M.A.H.); (R.D.); (B.T.); (Y.A.M.); (M.A.); (S.M.); (D.F.O.); (H.J.C.)
| | - Partha Protim Sarker
- ABEx Bio-Research Center, East Azampur, Dhaka 1230, Bangladesh; (M.J.U.); (P.P.S.)
- Department of Biotechnology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh
| | - Mahboob Alam
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea; (M.A.H.); (R.D.); (B.T.); (Y.A.M.); (M.A.); (S.M.); (D.F.O.); (H.J.C.)
- Division of Chemistry and Biotechnology, Dongguk University, Gyeongju 780-714, Korea
| | - Md. Mohibbullah
- Department of Fishing and Post Harvest Technology, Sher-e-Bangla Agricultural University, Sher-e-Bangla Nagar, Dhaka 1207, Bangladesh;
| | - Md. Nazmul Haque
- Department of Fisheries Biology and Genetics, Patuakhali Science and Technology University, Patuakhali 8602, Bangladesh;
| | - Israt Jahan
- Department of Pharmacy, Faculty of Life and Earth Sciences, Jagannath University, Dhaka 1100, Bangladesh;
| | - Md. Tahmeed Hossain
- Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh; (A.A.M.S.); (M.T.H.); (M.T.-U.-A.)
| | - Tania Afrin
- Interdisciplinary Institute for Food Security, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh;
| | - Md. Mahbubur Rahman
- Research and Development Center, KNOTUS Co., Ltd., Yeounsu-gu, Incheon 22014, Korea;
| | - Md. Tahjib-Ul-Arif
- Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh; (A.A.M.S.); (M.T.H.); (M.T.-U.-A.)
| | - Sarmistha Mitra
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea; (M.A.H.); (R.D.); (B.T.); (Y.A.M.); (M.A.); (S.M.); (D.F.O.); (H.J.C.)
| | - Diyah Fatimah Oktaviani
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea; (M.A.H.); (R.D.); (B.T.); (Y.A.M.); (M.A.); (S.M.); (D.F.O.); (H.J.C.)
| | - Md Kawsar Khan
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh;
- Department of Biological Sciences, Macquarie University, Sydney, NSW 2109, Australia
| | - Ho Jin Choi
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea; (M.A.H.); (R.D.); (B.T.); (Y.A.M.); (M.A.); (S.M.); (D.F.O.); (H.J.C.)
| | - Il Soo Moon
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea; (M.A.H.); (R.D.); (B.T.); (Y.A.M.); (M.A.); (S.M.); (D.F.O.); (H.J.C.)
| | - 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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Khalil M, Bazzi A, Zeineddine D, Jomaa W, Daher A, Awada R. Repressive effect of Rhus coriaria L. fruit extracts on microglial cells-mediated inflammatory and oxidative stress responses. JOURNAL OF ETHNOPHARMACOLOGY 2021; 269:113748. [PMID: 33359864 DOI: 10.1016/j.jep.2020.113748] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 12/13/2020] [Accepted: 12/19/2020] [Indexed: 05/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Rhus coriaria L. represents a herbal shrub that is used widely in traditional medicine in the Middle East region to treat different diseases including inflammation-related disorders. R. coriaria extracts have been well characterized in terms of their biological activities, pharmacological potential and phytochemical components. However, the effect of R. coriaria on neuro-inflammation has not been studied previously in detail. AIM OF THE STUDY In the present study, we performed a qualitative phytochemical analysis and investigated the antioxidant and anti-neuro-inflammatory potential of R. coriaria extracts on BV-2 microglial cells. MATERIALS AND METHODS R. coriaria extracts were prepared using two different solvents: distilled water and ethanol. Phytochemical screening was performed to determine the principal bioactive components. The radical scavenging activity was assessed by DPPH method (2,2-diphenyl-1-picrylhydrazyl). The effect of R. coriaria on neuro-inflammation was studied upon measuring the production of oxidative stress and inflammatory factors using DCF (2',7'-dichlorofluorescein) and Nitric oxide (NO) assays respectively, and by analyzing the mRNA (TNFα, IL-10, iNOS and COX-2) and protein (NFκβ) levels of genes involved BV-2 microglia cells-mediated inflammation using quantitative Real Time PCR and Western blot, respectively. RESULTS We found that R. coriaria extracts contain high phenolic and flavonoid contents. Interestingly, the ethanolic extract exerted a potent anti-inflammatory potential on insulted BV-2 cells manifested by: i) inhibition of Reactive Oxygen species (ROS) production and nitric oxide (NO) release; ii) suppressing TNFα, iNOS and COX-2 mRNA levels; iii) reducing NFκβ activation; and iiii) enhancing IL-10 transcription levels. CONCLUSION Our results indicate that the neuro-inflammation inhibitory activity of R. coriaria extracts involves the inhibition of NF-κB signaling pathway. These findings suggest that R. coriaria might carry therapeutic potential against neurodegenerative diseases.
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Affiliation(s)
- Mohamad Khalil
- Anti-cancer Therapeutic Approaches Group (ATAC), Rammal Rammal Laboratory, Biology Department, Faculty of Sciences, Lebanese University, Lebanon; Department of Earth, Environment and Life Sciences (DISTAV), University of Genova, Corso Europa 26, 16132, Genova, Italy
| | - Ali Bazzi
- Anti-cancer Therapeutic Approaches Group (ATAC), Rammal Rammal Laboratory, Biology Department, Faculty of Sciences, Lebanese University, Lebanon
| | - Dana Zeineddine
- Anti-cancer Therapeutic Approaches Group (ATAC), Rammal Rammal Laboratory, Biology Department, Faculty of Sciences, Lebanese University, Lebanon
| | - Wissam Jomaa
- Anti-cancer Therapeutic Approaches Group (ATAC), Rammal Rammal Laboratory, Biology Department, Faculty of Sciences, Lebanese University, Lebanon
| | - Ahmad Daher
- Anti-cancer Therapeutic Approaches Group (ATAC), Rammal Rammal Laboratory, Biology Department, Faculty of Sciences, Lebanese University, Lebanon; Doctoral School of Science and Technology, Research Platform for Environmental Science (PRASE), Lebanese University, Lebanon
| | - Rana Awada
- Anti-cancer Therapeutic Approaches Group (ATAC), Rammal Rammal Laboratory, Biology Department, Faculty of Sciences, Lebanese University, Lebanon; Doctoral School of Science and Technology, Research Platform for Environmental Science (PRASE), Lebanese University, Lebanon.
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Gao X, He D, Liu D, Hu G, Zhang Y, Meng T, Su Y, Zhou A, Huang B, Du J, Fu S. Beta-naphthoflavone inhibits LPS-induced inflammation in BV-2 cells via AKT/Nrf-2/HO-1-NF-κB signaling axis. Immunobiology 2020; 225:151965. [PMID: 32747020 DOI: 10.1016/j.imbio.2020.151965] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 05/06/2020] [Accepted: 05/24/2020] [Indexed: 01/15/2023]
Abstract
Numerous studies have shown that over-activation of microglia could cause neuroinflammation and release pro-inflammatory mediators, which could result in neurodegenerative diseases, like Parkinson's disease, Alzheimer's disease etc. Beta-naphthoflavone (BNF) has anti-oxidant and anti-inflammatory effects in borderline tissues, but BNF has not been reported the effect associated with neuroinflammation. Therefore, the purpose of this experiment is to inquiry the impact and mechanism of BNF on neuroinflammation. The results indicated that BNF significantly inhibited the production of pro-inflammatory mediators (inducible nitric-oxide synthase (iNOS), Cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) andinterleukin-6 (IL-6)) in LPS-exposed BV-2 cells. Analysis of western blot results found that BNF accelerated the activation of AKT/Nrf-2/HO-1 signaling pathway and suppressed NF-κB pathway activation. Further study showed that BNF inhibited activation of NF-κB pathway via promoting HO-1, and SnPP IX (a HO-1 inhibitor) could inhibit anti-inflammatory function of BNF. We also found that BNF reduced the apoptosis rate of Human neuroblastoma cells (SHSY5Y) and mouse hippocampal neuron cell line (HT22) by inhibiting release of inflammatory mediators in LPS-exposed BV2 cells. In a word, our results suggested that BNF could inhibit inflammatory response via AKT/Nrf-2/HO-1-NF-κB signaling axis in BV-2 cells and exerts neuroprotective impact via inhibiting the activation of BV2 cells.
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Affiliation(s)
- Xiyu Gao
- College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
| | - Dewei He
- College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
| | - Dianfeng Liu
- College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
| | - Guiqiu Hu
- College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
| | - Yufei Zhang
- College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
| | - Tianyu Meng
- College of Food Science and Engineering, Jilin University, Changchun, China.
| | - Yingchun Su
- College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
| | - Ang Zhou
- College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
| | - Bingxu Huang
- College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
| | - Jian Du
- College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
| | - Shoupeng Fu
- College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
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Cui N, Luo H, Zhao Y. Protective effect of GYY4137, a water‑soluble hydrogen sulfide‑releasing molecule, on intestinal ischemia‑reperfusion. Mol Med Rep 2020; 21:1633-1639. [PMID: 32016475 DOI: 10.3892/mmr.2020.10961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Accepted: 10/16/2019] [Indexed: 11/06/2022] Open
Abstract
The present study aimed to clarify the protective effects of p‑methoxyphenyl morpholino‑phosphinodithioic acid (GYY4137), a water‑soluble hydrogen sulfide‑releasing molecule, on a rat model of intestinal ischemia‑reperfusion (IIR). A total of 40 healthy male Sprague Dawley (SD) rats were randomly divided into four groups (n=10/group): Group A, a sham‑surgery group; Group B, the IIR group; group C, rats with IIR that were administered an abdominal injection of low‑dose GYY4137 (40 mg/kg); and group D, rats with IIR that were administered high‑dose GYY4137 (80 mg/kg). Intestinal histomorphology was observed using hematoxylin and eosin staining, and the concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured. Apoptotic index (AI) was determined by terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling. Reverse transcription‑quantitative PCR analysis was performed to assess the expression levels of intestinal caspase‑3, Bax and Bcl‑2. Notably, disordered arrangement of intestinal villi and mucosal necrosis were detected in group B, which was substantially improved by GYY4137 treatment (groups C and D). MDA content (nmol/mg) was 2.83±0.36, 9.23±0.78, 4.97±0.45 and 3.51±1.05 nmol/mg in groups A, B, C and D, respectively. In addition, SOD concentration (U/mg) was 135.37±3.34, 76.45±1.39, 95.13±1.64 and 115.13±2.54 in groups A, B, C and D, respectively. Furthermore, AI in group B (21.73±1.17%) was markedly higher than that in group A (4.53±0.28%) and in the GYY4137 intervention groups (9.53±0.96 and 6.53±0.76% in groups C and D, respectively). Compared with in group A, the mRNA expression levels of Bax and caspase‑3 were markedly higher in group B (P<0.05), whereas the expression of Bcl‑2 was significantly lower (P<0.05). Furthermore, compared with in group B, Bcl‑2 expression was higher, and Bax and caspase‑3 expression was lower in groups C and D (P<0.05). In conclusion, GYY4137 may alleviate IIR‑induced damage in SD rats.
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Affiliation(s)
- Ning Cui
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Hesheng Luo
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Yu Zhao
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
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Role of Oxidative Stress, MAPKinase and Apoptosis Pathways in the Protective Effects of Thymoquinone Against Acrylamide-Induced Central Nervous System Toxicity in Rat. Neurochem Res 2019; 45:254-267. [PMID: 31728856 DOI: 10.1007/s11064-019-02908-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Revised: 10/28/2019] [Accepted: 11/08/2019] [Indexed: 12/24/2022]
Abstract
The present study evaluated biochemical endpoints characterizing acrylamide (ACR) neurotoxicity in the cortex of rats, following the possible neuroprotective activity of thymoquinone (TQ), an active constituent of Nigella sativa. ACR (50 mg/kg, intraperitoneal [i.p.]) concurrently with TQ (2.5, 5 and 10 mg/kg, i.p.) for 11 days were administered to rats. As positive control, vitamin E was used. After 11 days of injections, narrow beam test (NBT) was performed. The levels of reduced glutathione (GSH) and malondialdehyde (MDA) were measured and Western blotting was done for mitogen-activated protein kinases (MAPKinases) and apoptosis pathways proteins in the rats' cortex. Additionally, Evans blue assay was done to evaluate the integrity of blood brain barrier (BBB). Administration of ACR significantly induced gait abnormalities. A significant decrease and increase in the levels of GSH and MDA was observed in the cortex of ACR-treated rats, respectively. The elevation in the levels of caspases 3 and 9, glial fibrillary acidic protein (GFAP) content, and Bax/Bcl-2, P-P38/P38 and P-JNK/JNK ratios accompanied by reduction in myelin basic protein (MBP) content and P-ERK/ERK ratio were noticed in the ACR group. TQ (5 mg/kg) improved gait abnormalities, and restored these changes. ACR affected the integrity of BBB while TQ was able to maintain the integrity of this barrier. TQ reversed the alterations in the protein contents of MAP kinase and apoptosis signaling pathways as well as MBP and GFAP contents, induced by ACR. It protected against ACR-mediated neurotoxicity, partly through its antioxidant and antiapoptotic properties.
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Antioxidant properties of probucol released from mesoporous silica. Eur J Pharm Sci 2019; 138:105038. [PMID: 31398394 DOI: 10.1016/j.ejps.2019.105038] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 07/15/2019] [Accepted: 08/05/2019] [Indexed: 11/21/2022]
Abstract
Antioxidants play a vital role in scavenging reactive oxygen species (ROS) produced by the reduction of molecular oxygen from various cellular mechanisms. Under oxidative stress, an increase in the levels of ROS overwhelms the antioxidant response, causing oxidative damage to biological molecules, and leading to the development of various diseases. Drug compounds with potent antioxidant properties are typically poorly water soluble and highly hydrophobic. An extreme case is Probucol (PB), a potent antioxidant with reported water solubility of 5 ng/ml, and oral bioavailiability of <10%. In this study, PB was loaded in mesoporous silica at various drug loadings to understand the changes to the physical properties of the loaded drug, and it's in vitro drug release. Further in vitro studies were conducted in endothelial and microglia cell models to compare the free radical scavening efficiency of ascorbic acid, PB, and PB release from mesoporous silica particles. Out of the three different mesostructured particles studied, the maximum loading of PB was achieved for large pore mesoporous particles (SBA-15) at 50 wt% drug loading, before complete pore filling was observed. For all materials, loadings above complete pore filling resulted in the recrystallization of PB on the external surface. In vitro drug release measurements showed a rapid dissolution rate at low drug loadings compared to a bimodal release profile of amorphous and crystalline drug at higher drug loadings. PB loaded in mesoporous particle was shown to enhance the antioxidant response to extracellular ROS in the endothelial cell line model, and to intracellular ROS in the microglia cell model. Our results indicate that the antioxidant properties of PB can be significantly improved by using mesoporous silica as a delivery vehicle.
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Zhang Y, Li C, Zhou C, Hong P, Zhang Y, Sun S, Qian ZJ. 2'-Hydroxy-5'-methoxyacetophenone attenuates the inflammatory response in LPS-induced BV-2 and RAW264.7 cells via NF-κB signaling pathway. J Neuroimmunol 2019; 330:143-151. [PMID: 30884275 DOI: 10.1016/j.jneuroim.2019.03.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 03/11/2019] [Accepted: 03/11/2019] [Indexed: 02/07/2023]
Abstract
Seahorse has been used as a traditional medicine in Southeast Asian countries for a long time. A compound, 2'-Hydroxy-5'-Methoxyacetophenone (2H5M) isolated from seahorse, Hippocampus kuda, was tested for its anti-inflammatory effect in lipopolysaccharides (LPS)-stimulated BV-2 cells and RAW264.7 cells. MTT assay indicated that 2H5M has no cytotoxicity on two kinds of cells. The concentration of nitric oxide (NO) measured by Griess Reaction System showed that 2H5M could significantly inhibit the NO concentration. The ELISA results showed that 2H5M could suppress the secretion of TNF-α in a dose-dependent manner. Moreover, western blot analysis was utilized to measure the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways. Electrophoretic mobility shift assay (EMSA) demonstrated that 2H5M reduced NF-κB DNA binding activity. Furthermore, the molecular docking study showed that 2H5M can form active sites with NF-κB. Collectively, these results indicated that 2H5M possesses anti-inflammatory effects and may have a potential application in inflammatory disorders in the future.
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Affiliation(s)
- YuanYuan Zhang
- School of Chemistry and Environment of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China; College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
| | - ChengYong Li
- School of Chemistry and Environment of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China; Shenzhen Institute of Guangdong Ocean University, Shenzhen 518108, China
| | - ChunXia Zhou
- College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; Shenzhen Institute of Guangdong Ocean University, Shenzhen 518108, China
| | - PengZhi Hong
- College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
| | - Yi Zhang
- College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
| | - ShengLi Sun
- School of Chemistry and Environment of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China
| | - Zhong-Ji Qian
- School of Chemistry and Environment of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China; Shenzhen Institute of Guangdong Ocean University, Shenzhen 518108, China.
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Üstün R, Oğuz EK, Şeker A, Korkaya H. Thymoquinone protects DRG neurons from axotomy-induced cell death. Neurol Res 2018; 40:930-937. [PMID: 30088803 DOI: 10.1080/01616412.2018.1504157] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
OBJECTIVE Peripheral nerve injury (PNI) is a significant health problem that is linked to sensory, motor, and autonomic deficits. This pathological condition leads to a reduced quality of life in most affected individuals. Schwann cells (SCs) play a crucial role in the repair of PNI. Effective agents that promote SC activation may facilitate and accelerate peripheral nerve repair. Thymoquinone (TQ), a bioactive component of Nigella sativa seeds, has an antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective properties. In the present study, the neuroprotective efficacy of TQ was investigated by using a laser microdissection technique in a mouse PNI model. METHODS Single cells were isolated from dorsal root ganglions (DRGs) of 6-8-week-old mice, maintained in defined culture conditions and treated with or without TQ at different concentrations. Axons were cut (axotomy) using a controllable laser microbeam to model axonal injury in vitro. Under fluorescence microscopy, cell viability was evaluated using the fluorescent dyes. The behavior of the cells was continuously monitored with time-lapse video microscopy. RESULTS TQ significantly increased neuronal survival by promoting the survival and proliferation of SCs and fibroblasts, as well as the migration of SCs. Furthermore, TQ improved the ability to extend neurites of axotomized neurons. The regenerative effect of TQ was dose-dependent suggesting a target specificity. Our studies warrant further preclinical and clinical investigations of TQ as a potential regenerative agent to treat peripheral nerve injuries. CONCLUSION TQ exhibits a regenerative potential for the treatment of damaged peripheral nerves.
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Affiliation(s)
- Ramazan Üstün
- a Department of Physiology, Faculty of Medicine , Van Yüzüncü Yıl University , Van , Turkey.,b Neuroscience Research Unit, Faculty of Medicine , Van Yüzüncü Yıl University , Van , Turkey
| | - Elif Kaval Oğuz
- b Neuroscience Research Unit, Faculty of Medicine , Van Yüzüncü Yıl University , Van , Turkey
| | - Ayşe Şeker
- a Department of Physiology, Faculty of Medicine , Van Yüzüncü Yıl University , Van , Turkey
| | - Hasan Korkaya
- c Department of Biochemistry and Molecular Biology, Georgia Cancer Center , Augusta University , Augusta , GA , USA
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Cobourne-Duval MK, Taka E, Mendonca P, Soliman KFA. Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NFκB pathway signaling targets in LPS/IFNγ -activated BV-2 microglia cells. J Neuroimmunol 2018; 320:87-97. [PMID: 29759145 PMCID: PMC5967628 DOI: 10.1016/j.jneuroim.2018.04.018] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 04/17/2018] [Accepted: 04/30/2018] [Indexed: 12/22/2022]
Abstract
Neuroinflammation and microglial activation are pathological markers of a number of central nervous system (CNS) diseases. Chronic activation of microglia induces the release of excessive amounts of reactive oxygen species (ROS) and pro-inflammatory cytokines. Additionally, chronic microglial activation has been implicated in several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Thymoquinone (TQ) has been identified as one of the major active components of the natural product Nigella sativa seed oil. TQ has been shown to exhibit anti-inflammatory, anti-oxidative, and neuroprotective effects. In this study, lipopolysaccharide (LPS) and interferon gamma (IFNγ) activated BV-2 microglial cells were treated with TQ (12.5 μM for 24 h). We performed quantitative proteomic analysis using Orbitrap/Q-Exactive Proteomic LC-MS/MS (Liquid chromatography-mass spectrometry) to globally assess changes in protein expression between the treatment groups. Furthermore, we evaluated the ability of TQ to suppress the inflammatory response using ELISArray™ for Inflammatory Cytokines. We also assessed TQ's effect on the gene expression of NFκB signaling targets by profiling 84 key genes via real-time reverse transcription (RT2) PCR array. Our results indicated that TQ treatment of LPS/IFNγ-activated microglial cells significantly increased the expression of 4 antioxidant, neuroprotective proteins: glutaredoxin-3 (21 fold; p < 0.001), biliverdin reductase A (15 fold; p < 0.0001), 3-mercaptopyruvate sulfurtransferase (11 fold; p < 0.01), and mitochondrial lon protease (>8 fold; p < 0.001) compared to the untreated, activated cells. Furthermore, TQ treatment significantly (P < 0.0001) reduced the expression of inflammatory cytokines, IL-2 = 38%, IL-4 = 19%, IL-6 = 83%, IL-10 = 237%, and IL-17a = 29%, in the activated microglia compared to the untreated, activated which expression levels were significantly elevated compared to the control microglia: IL-2 = 127%, IL-4 = 151%, IL-6 = 670%, IL-10 = 133%, IL-17a = 127%. Upon assessing the gene expression of NFκB signaling targets, this study also demonstrated that TQ treatment of activated microglia resulted in >7 fold down-regulation of several NFκB signaling targets genes, including interleukin 6 (IL6), complement factor B (CFB), chemokine (CC motif) ligand 3 (CXCL3), chemokine (CC) motif ligand 5 (CCL5) compared to the untreated, activated microglia. This modulation in gene expression counteracts the >10-fold upregulation of these same genes observed in the activated microglia compared to the controls. Our results show that TQ treatment of LPS/IFNγ-activated BV-2 microglial cells induce a significant increase in expression of neuroprotective proteins, a significant decrease in expression inflammatory cytokines, and a decrease in the expression of signaling target genes of the NFκB pathway. Our findings are the first to show that TQ treatment increased the expression of these neuroprotective proteins (biliverdin reductase-A, 3-mercaptopyruvate sulfurtransferase, glutaredoxin-3, and mitochondrial lon protease) in the activated BV-2 microglial cells. Additionally, our results indicate that TQ treatment decreased the activation of the NFκB signaling pathway, which plays a key role in neuroinflammation. In conclusion, our results demonstrate that TQ treatment reduces the inflammatory response and modulates the expression of specific proteins and genes and hence potentially reduce neuroinflammation and neurodegeneration driven by microglial activation.
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Affiliation(s)
- Makini K Cobourne-Duval
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, United States
| | - Equar Taka
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, United States
| | - Patricia Mendonca
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, United States
| | - Karam F A Soliman
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, United States.
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Zhang YY, Zhang Y, Yao YB, Lei XL, Qian ZJ. Butyrolactone-I from Coral-Derived Fungus Aspergillus terreus Attenuates Neuro-Inflammatory Response via Suppression of NF-κB Pathway in BV-2 Cells. Mar Drugs 2018; 16:E202. [PMID: 29880753 PMCID: PMC6025369 DOI: 10.3390/md16060202] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 05/23/2018] [Accepted: 06/06/2018] [Indexed: 12/11/2022] Open
Abstract
Butyrolactone-I (ZB5-1) from the coral-derived fungus Aspergillus terreus was investigated in this study to estimate its anti-neuroinflammatory effects on lipopolysaccharide (LPS)-induced BV-2 microglia cells. MTT assay indicated that ZB5-1 in tested concentrations had no cytotoxicity on BV-2 cells, and significantly reduced the production of nitric oxide (NO), measured using Griess reagent, and interleukin-1 beta (IL-1β), detected by enzyme-linked immunosorbent assay (ELISA). ZB5-1 also down-regulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner by Western blot analysis. Moreover, the effect of ZB5-1 on the nuclear factor-κB (NF-κB) signaling pathway was studied via the expression of phosphorylation of NF-κB p65 and inhibitor of NF-κB (IκB), and the nuclear translocation of NF-κB p65 respectively. The results showed that ZB5-1 could inhibit the phosphorylation of p65 and IκB. Furthermore, molecular docking study suggested that ZB5-1 bound at the active sites of NF-κB to prevent its translocation to the nucleus. Therefore, we suggest ZB5-1 has a potential to reduce the anti-inflammatory response in LPS-induced BV-2 cells.
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Affiliation(s)
- Yuan Yuan Zhang
- College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China.
| | - Yi Zhang
- College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China.
- Shenzhen Institute of Guangdong Ocean University, Shenzhen 518108, China.
| | - Yuan-Bei Yao
- College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China.
| | - Xiao-Ling Lei
- College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China.
| | - Zhong-Ji Qian
- Shenzhen Institute of Guangdong Ocean University, Shenzhen 518108, China.
- College of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China.
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Ruiz-Roso MB, Olivares-Álvaro E, Quintela JC, Ballesteros S, Espinosa-Parrilla JF, Ruiz-Roso B, Lahera V, de Las Heras N, Martín-Fernández B. Effects of Low Phytanic Acid-Concentrated DHA on Activated Microglial Cells: Comparison with a Standard Phytanic Acid-Concentrated DHA. Neuromolecular Med 2018; 20:328-342. [PMID: 29846873 DOI: 10.1007/s12017-018-8496-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 05/24/2018] [Indexed: 02/04/2023]
Abstract
Docosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 (ω-3) long chain polyunsaturated fatty acid of neuronal membranes involved in normal growth, development, and function. DHA has been proposed to reduce deleterious effects in neurodegenerative processes. Even though, some inconsistencies in findings from clinical and pre-clinical studies with DHA could be attributed to the presence of phytanic acid (PhA) in standard DHA treatments. Thus, the aim of our study was to analyze and compare the effects of a low PhA-concentrated DHA with a standard PhA-concentrated DHA under different neurotoxic conditions in BV-2 activated microglial cells. To this end, mouse microglial BV-2 cells were stimulated with either lipopolysaccharide (LPS) or hydrogen peroxide (H2O2) and co-incubated with DHA 50 ppm of PhA (DHA (PhA:50)) or DHA 500 ppm of PhA (DHA (PhA:500)). Cell viability, superoxide anion (O2-) production, Interleukin 6 (L-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), glutathione peroxidase (GtPx), glutathione reductase (GtRd), Caspase-3, and the brain-derived neurotrophic factor (BDNF) protein expression were explored. Low PhA-concentrated DHA protected against LPS or H2O2-induced cell viability reduction in BV-2 activated cells and O2- production reduction compared to DHA (PhA:500). Low PhA-concentrated DHA also decreased COX-2, IL-6, iNOS, GtPx, GtRd, and SOD-1 protein expression when compared to DHA (PhA:500). Furthermore, low PhA-concentrated DHA increased BDNF protein expression in comparison to DHA (PhA:500). The study provides data supporting the beneficial effect of low PhA-concentrated DHA in neurotoxic injury when compared to a standard PhA-concentrated DHA in activated microglia.
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Affiliation(s)
- María Belén Ruiz-Roso
- Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain
| | - Elena Olivares-Álvaro
- Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain
| | | | - Sandra Ballesteros
- Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain
| | | | - Baltasar Ruiz-Roso
- Department of Nutrition and Bromatology I (Nutrition), Faculty of Pharmacy, Complutense University, 28040, Madrid, Spain
| | - Vicente Lahera
- Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain
| | - Natalia de Las Heras
- Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain
| | - Beatriz Martín-Fernández
- Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain.
- Natac Biotech S.L., 28923, Alcorcón, Madrid, Spain.
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Farkhondeh T, Samarghandian S, Shahri AMP, Samini F. The Neuroprotective Effects of Thymoquinone: A Review. Dose Response 2018; 16:1559325818761455. [PMID: 29662431 PMCID: PMC5898665 DOI: 10.1177/1559325818761455] [Citation(s) in RCA: 88] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 10/26/2017] [Accepted: 11/14/2017] [Indexed: 12/12/2022] Open
Abstract
Thymoquinone (TQ), one of the main components active of Nigella sativa, exhibited very useful biomedical effects such as anti-inflammatory, antioxidant, antimicrobial, antiparasitic, anticancer, hypoglycemic, antihypertensive, and antiasthmatic effects. There are several studies about pharmacological activities of TQ but its neuroprotection effects are not fully described. The literature search has indicated many studies pertaining to the effects of TQ in neurological problems such as epilepsy, parkinsonism, anxiety, and improvement of learning and memory, and so on. In addition, TQ protected brain cells from various injuries due to its antioxidant, anti-inflammatory, and apoptotic effects in cell line and experimental animal models. The present study has been designed to review the scientific literature about the pharmacological activities of TQ to the neurological diseases. This study purposed that although experimental studies indicated the beneficial effects of TQ against nervous system problems, better designed clinical trials in humans are needed to confirm these effects.
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Affiliation(s)
- Tahereh Farkhondeh
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Saeed Samarghandian
- Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | | | - Fariborz Samini
- Department of Neurosurgery, Faculty of Medicine, Mashhad University of Medical Sciences, Mahhad, Iran
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Cascella M, Bimonte S, Barbieri A, Del Vecchio V, Muzio MR, Vitale A, Benincasa G, Ferriello AB, Azzariti A, Arra C, Cuomo A. Dissecting the Potential Roles of Nigella sativa and Its Constituent Thymoquinone on the Prevention and on the Progression of Alzheimer's Disease. Front Aging Neurosci 2018; 10:16. [PMID: 29479315 PMCID: PMC5811465 DOI: 10.3389/fnagi.2018.00016] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2017] [Accepted: 01/12/2018] [Indexed: 01/31/2023] Open
Abstract
Several nutraceuticals have been investigated for preventing or retarding the progression of different neurodegenerative diseases, including Alzheimer's disease (AD). Because Nigella sativa (NS) and its isolated compound thymoquinone (TQ) have significant anti-oxidant and anti-inflammatory proprieties, they could represent effective neuroprotective agents. The purpose of this manuscript is to analyze and to recapitulate the results of in vitro and in vivo studies on the potential role of NS/TQ in AD's prevention and treatment. The level of evidence for each included animal study has been assessed by using a modified CAMARADES (Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies) 10-item checklist. We used MEDLINE and EMBASE databases to screen relevant articles published up to July 2017. A manual search was also performed. The database search yielded 38 studies, of which 18 were included in this manuscript. Results from these approaches suggest that NS or TQ could represent an effective strategy against AD due to the balancing of oxidative processes and the binding to specific intracellular targets. The overall effects mainly regard the prevention of hippocampal pyramidal cell loss and the increased cognitive functions.
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Affiliation(s)
- Marco Cascella
- Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy
| | - Sabrina Bimonte
- Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy
| | - Antonio Barbieri
- S.S.D. Sperimentazione Animale, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy
| | - Vitale Del Vecchio
- S.S.D. Sperimentazione Animale, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy
| | - Maria Rosaria Muzio
- Division of Infantile Neuropsychiatry, UOMI-Maternal and Infant Health, Naples, Italy
| | | | | | | | - Amalia Azzariti
- Experimental Pharmacology Laboratory, IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy
| | - Claudio Arra
- S.S.D. Sperimentazione Animale, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy
| | - Arturo Cuomo
- Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy
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Bargi R, Asgharzadeh F, Beheshti F, Hosseini M, Sadeghnia HR, Khazaei M. The effects of thymoquinone on hippocampal cytokine level, brain oxidative stress status and memory deficits induced by lipopolysaccharide in rats. Cytokine 2017; 96:173-184. [PMID: 28432986 DOI: 10.1016/j.cyto.2017.04.015] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 03/31/2017] [Accepted: 04/11/2017] [Indexed: 01/05/2023]
Abstract
OBJECTIVE The study objective was to determine the protective effects of thymoquinone (TQ) on brain tissues oxidative stress status, hippocampal cytokine level, and learning and memory deficits induced by lipopolysaccharide (LPS) in rats. METHODS Animals were randomly divided into the following groups and treated: (1) Control (saline), (2) LPS (1mg/kg i.p.), (3-5) 2, 5 or 10mg/kg TQ extract 30min before LPS injection. The treatment was started since two weeks before the behavioral experiments and continued during the behavioral tests (LPS injected 2h before each behavioral experiment). Finally, the brains were removed for biochemical assessments. RESULTS Morris water maze (MWM) test results showed that LPS increased escape latency compared to control group whereas TQ decreased them vs. LPS group. In passive avoidance (PA) test, LPS reduced the latency to enter the dark compartment vs. control group, while TQ treatment attenuated this effect of LPS. Additionally, LPS increased interleukin-6 (IL-6) and tumor necrosis alpha (TNF-α) in the hippocampal tissues. It also elevated malondialdehyde (MDA) and nitric oxide (NO) metabolites and decreased thiol content, superoxide dismutase (SOD) and catalase (CAT) in both hippocampus and cortex vs. control group, while TQ decreased IL-6, TNF-α, MDA and NO metabolites and increased thiol content, SOD and CAT compared to LPS group. CONCLUSION Findings of current study indicated that TQ improved LPS-induced learning and memory impairments induced by LPS in rats by attenuating the hippocampal cytokine levels and brain tissues oxidative damage.
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Affiliation(s)
- Rahimeh Bargi
- Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fereshteh Asgharzadeh
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farimah Beheshti
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahmoud Hosseini
- Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Hamid Reza Sadeghnia
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Khazaei
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Karaca G, Aydin O, Pehlivanli F, Altunkaya C, Uzun H, Güler O. Effectiveness of thymoquinone, zeolite, and platelet-rich plasma in model of corrosive oesophagitis induced in rats. Ann Surg Treat Res 2017; 92:396-401. [PMID: 28580343 PMCID: PMC5453871 DOI: 10.4174/astr.2017.92.6.396] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 01/20/2017] [Accepted: 01/23/2017] [Indexed: 01/08/2023] Open
Abstract
Purpose The effectiveness of platelet-rich plasma (PRP), thymoquinone, and zeolite in corrosive esophageal burns was investigated in a rat model. Methods Four groups were comprised as containing 10 rats in each group. For group I, oesophagitis was induced and no other procedure was performed (control group). For group II, oesophagitis was induced and thymoquinone was administered for 1 week via oral gavage once a day (thymoquinone group). For group III, oesophagitis was induced for 1 week via oral gavage once a day (PRP group). For group IV, oesophagitis was induced and zeolite was administered for 1 week via oral gavage once a day (zeolite group). On the 10th day, the rats were sacrificed under anaesthesia and venous blood sampling was performed from the vena portae. The oesophaguses were totally excised. Biochemically, interleukin (IL)-1B, IL-6, TNF-α, and MCP-1 were examined from venous blood. Inflammation score was evaluated histopathologically in oesophageal tissue that was collected. Results There was a statistically significant difference among groups in terms of IL-1, IL-6, MCP levels, compared to the control group; median IL-1, IL-6, MCP levels of thymoquinone, PRP, and zeolite groups were statistically significantly lower. There was a statistically significant difference among groups in terms of inflammation scores, compared to group I; median inflammation scores of groups II, III and IV were statistically significantly lower thymoquinone. Conclusion PRP, and zeolite exhibited positive effect on recovery in oesophagitis by reducing inflammation in the involved segment.
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Affiliation(s)
- Gökhan Karaca
- Department of General Surgery, Faculty of Medicine, Kırıkkale University, Kırıkkale, Turkey
| | - Oktay Aydin
- Department of General Surgery, Faculty of Medicine, Kırıkkale University, Kırıkkale, Turkey
| | - Faruk Pehlivanli
- Department of General Surgery, Faculty of Medicine, Kırıkkale University, Kırıkkale, Turkey
| | - Canan Altunkaya
- Department of General Surgery, Faculty of Medicine, Kırıkkale University, Kırıkkale, Turkey
| | - Hafize Uzun
- Department of Biochemistry, Istanbul University, Istanbul, Turkey
| | - Osman Güler
- Department of General Surgery, Faculty of Medicine, Kırıkkale University, Kırıkkale, Turkey
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