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Sobhannizadeh A, Giglou MT, Behnamian M, Estaji A, Majdi M, Szumny A. The effect of plant growth regulators, FeO 3-CTs nanoparticles and LEDs light on the growth and biochemical compounds of black seed (Nigella sativa L.) callus in vitro. BMC PLANT BIOLOGY 2025; 25:539. [PMID: 40281420 PMCID: PMC12032791 DOI: 10.1186/s12870-025-06423-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Accepted: 03/18/2025] [Indexed: 04/29/2025]
Abstract
BACKGROUND black seed (Nigella sativa L.) has long been utilized in traditional medicine and as a food ingredient due to its potential therapeutic properties including its effectiveness against cancer, coronaviruses, and bacterial infections. Recently, it has garnered significant attention for its rich reservoir of beneficial secondary metabolites. In vitro culture of black seeds presents an efficient and modern approach for the large-scale production of these valuable compounds, offering advantages such as space efficiency, reduced time, and lower costs. This study aimed to develop and optimize a protocol for callus induction and the identification of key secondary metabolites, including thymoquinone (TQ), phenolic compounds, and flavonoids. To induce callus formation in seed explants, two plant growth regulators (PGRs) were applied individually or in combination and incorporated into Murashige and Skoog (MS) culture medium. RESULTS The combination of Auxin, 2,4-dichlorophenoxyacetic acid (2,4-D) and cytokinin, 6-benzylaminopurine (BAP), effectively induced callus formation in most explants, with the response varying based on concentration. The highest callus fresh weight (7.02 g) was obtained on Red(R) LED lighting with FeO3-CTs nanoparticles (100 mg/L- 1), which also resulted in the highest dry weight (1.307 g) after 40 days of cultivation. Similarly, the highest levels of phenols, flavonoids and amino acids were observed under R LED with FeO3-CTs nanoparticles (100 mg L- 1), while FeO3-CTs nanoparticles at 100 and 200 mg/L- 1) exhibited significant effects on metabolite production. In contrast, the antioxidant activity against DPPH free radicals and total carbohydrate accumulation were enhanced in callus cultures treated with FeO3-CTs nanoparticles (200 mg/L- 1) under dark conditions. Additionally, GC-MS analysis revealed that FeO3-CTs nanoparticles (100 mg/L- 1) yielded the most effective enhancement of secondary metabolites under blue (B) LED light at a concentration of 295 mg/L- 1. CONCLUSION The finding of this study highlights the potential of the proposed method for the large-scale production of secondary metabolites, total carbohydrates, amino acids, phenolic compounds, and flavonoids from black seed callus cultures in a controlled environment. This optimized approach offers a cost-effective and space-efficient strategy for enhancing bioactive compound synthesis, with potential applications in pharmaceutical and nutraceutical industries.
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Affiliation(s)
- Ali Sobhannizadeh
- Department of Horticultural Sciences, Faculty of Agriculture and Natural Resources, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran
- Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Wrocław, Poland
| | - Mousa Torabi Giglou
- Department of Horticultural Sciences, Faculty of Agriculture and Natural Resources, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran.
| | - Mahdi Behnamian
- Department of Horticultural Sciences, Faculty of Agriculture and Natural Resources, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran
| | - Asghar Estaji
- Department of Horticultural Sciences, Faculty of Agriculture and Natural Resources, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran
| | - Mohammad Majdi
- Department of Plant Production and Genetics, Faculty of Agriculture, University of Kurdistan, P. O. Box 416, Sanandaj, Iran
| | - Antoni Szumny
- Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
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Toprak V, Özdemir İ, Öztürk Ş, Yanar O, Kizildemir YZ, Tuncer MC. Thymoquinone Enhances Doxorubicin Efficacy via RAS/RAF Pathway Modulation in Ovarian Adenocarcinoma. Pharmaceutics 2025; 17:536. [PMID: 40284530 PMCID: PMC12030150 DOI: 10.3390/pharmaceutics17040536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 04/14/2025] [Accepted: 04/17/2025] [Indexed: 04/29/2025] Open
Abstract
Background/Objectives: Ovarian cancer remains one of the most commonly diagnosed malignancies among women worldwide. The heterogeneity among tumor subtypes and the emergence of treatment resistance have raised significant concerns regarding the long-term efficacy of chemotherapy, radiotherapy, and immunotherapy. In response to these challenges, drug repurposing strategies-utilizing existing drugs in novel therapeutic contexts-have gained increasing attention. This study aimed to investigate the cytotoxic and apoptotic effects of the combined application of doxorubicin (DX) and thymoquinone (TQ) on ovarian adenocarcinoma cells (OVCAR3). Methods: OVCAR3 cells were cultured in RPMI medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin. Cell viability and proliferation were assessed using the MTT assay following treatment with various concentrations of DX and TQ. NucBlue immunofluorescence staining was employed to examine nuclear morphology and to identify apoptosis-associated changes. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was per-formed to evaluate the expression levels of apoptosis-related and oncogenic pathway genes, including RAF, RAS, Bcl-2, and Bax. Results: The results demonstrated that the combination of DX and TQ significantly reduced OVCAR3 cell viability and induced apoptosis in a dose-dependent manner. qRT-PCR analysis revealed a downregulation of RAS, RAF, and Bcl-2 expression, along with an upregulation of Bax, indicating activation of the intrinsic apoptotic pathway. These findings suggest that thymoquinone exerts an-ti-proliferative and pro-apoptotic effects by modulating the RAS/RAF signaling cascade. Furthermore, the co-administration of thymoquinone with doxorubicin potentiated these effects, suggesting a synergistic interaction between the two agents. Conclusions: Histopathological and molecular evaluations further confirmed the activation of apoptosis and the suppression of key oncogenic pathways. Collectively, these results underscore the therapeutic potential of thymoquinone as both a monotherapy and an adjuvant to conventional chemotherapy, warranting further validation in preclinical and clinical studies.
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Affiliation(s)
- Veysel Toprak
- Department of Gynecology and Obstetrics, Faculty of Medicine, Private Metrolife Hospital, Şanlıurfa 63320, Turkey;
| | - İlhan Özdemir
- Department of Gynecology and Obstetrics, Faculty of Medicine, Atatürk University, Erzurum 25070, Turkey;
| | - Şamil Öztürk
- Vocational School of Health Services, Çanakkale Onsekiz Mart University, Çanakkale 17100, Turkey;
| | - Orhan Yanar
- Department of Gynecology and Obstetrics, Private Nev Hospital, Şanlıurfa 63300, Turkey;
| | - Yusuf Ziya Kizildemir
- Department of Gynecology and Obstetrics, Şanlıurfa Training and Research Hospital, Şanlıurfa 63300, Turkey;
| | - Mehmet Cudi Tuncer
- Department of Anatomy, Faculty of Medicine, Dicle University, Diyarbakir 21200, Turkey
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Biswas P, Bose S, Chakraborty S. Vitamin D3 potentiates antimicrobial and antibiofilm activities of streptomycin and thymoquinone against Pseudomonas aeruginosa. World J Microbiol Biotechnol 2025; 41:104. [PMID: 40074989 DOI: 10.1007/s11274-025-04304-y] [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: 12/31/2024] [Accepted: 02/22/2025] [Indexed: 03/14/2025]
Abstract
Biofilm formed by Pseudomonas aeruginosa is a three dimensional microbial matrix that confers multidrug resistance properties along with the proficiency to evade the host immune system. The present study aims to determine the combinatorial effects of vitamin D3 (cholecalciferol) with two already reported antibiofilm agents: streptomycin and thymoquinone separately against P. aeruginosa biofilms. The minimum inhibitory concentration of streptomycin, thymoquinone and D3 was found to be 20, 10 and 100 μg/mL respectively. The inhibition of biofilm formation and pre-formed biofilm disintegration properties of streptomycin and thymoquinone alone or in combination with D3 at their sub-MIC concentration was determined by crystal violet staining and confocal laser scanning microscopy. A significant inhibition of metabolic activities like oxygen consumption rate and reduction in quorum sensing related cellular activities like swarming motilities, pyocyanin production and extracellular protease secretion by P. aeruginosa were also observed as a result of this combinatorial effect. Both of these combinatorial applications were found to accumulate ROS in bacterial cells, which has been proved to be one of the main causes of their antibiofilm activity. Effect of these two drug combinations on bacterial lettuce leaf infection was also evaluated. Molecular docking analysis indicated that thymoquinone combined D3 can interact more efficiently with the quorum sensing proteins LasI and LasR. The host cell cytotoxicity of these two combinations was found to be negligible on the murine macrophage cell line. These findings suggest that D3 potentiates the antimicrobial and antibiofilm efficacy of both streptomycin and thymoquinone against P. aeruginosa. Although both combinations have shown significant antibiofilm and antimicrobial potential, combinatorial performances of D3 combined thymoquinone were found to be more promising.
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Affiliation(s)
- Priyam Biswas
- Department of Biochemistry, University of Calcutta, Kolkata, West Bengal, 700 019, India
| | - Soham Bose
- Department of Biochemistry, University of Calcutta, Kolkata, West Bengal, 700 019, India
| | - Sudipta Chakraborty
- Department of Microbiology, Government General Degree College, Narayangarh, Rathipur, Narayangarh, Midnapore, West Bengal, 721437, India.
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Sharma B, Shekhar H, Sahu A, Haque S, Kaur D, Tuli HS, Sharma U. Deciphering the anticancer potential of thymoquinone: in-depth exploration of the potent flavonoid from Nigella sativa. Mol Biol Rep 2025; 52:268. [PMID: 40016603 DOI: 10.1007/s11033-025-10375-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 02/20/2025] [Indexed: 03/01/2025]
Abstract
Since its first written description around 3000 BC until the present day, cancer has stood as a leading global cause of death, claiming the lives of 1 in 6 individuals. Due to its widespread impact and lethality, it remains one of the most explored yet most challenging disease for the global scientific community. Throughout history, various plant extracts have been used in treating numerous diseases, including cancer. These natural extracts are regaining attention due to their therapeutic benefits and lesser side effects. Thymoquinone, chemically 2-isopropyl-5-methylbenzo-1,4-quinone, constitutes the primary bioactive component of the plant Nigella sativa. Extensive research across in vivo, in vitro models, and clinical trials has revealed Thymoquinone's noteworthy therapeutic potential against cancer. Thymoquinone has shown promising anti-cancer activity in various cancers including breast cancer, lung cancer, prostate cancer, colorectal cancer, cervical cancer, pancreatic cancer, gastric cancer and blood cancers. However, there are challenges such as limited clinical trials, low bioavailability, and the need for more research to understand its long-term safety and effectiveness. This article provides a comprehensive and thorough review of thymoquinone, covering its effectiveness across various malignancies, the molecular signalling pathways it influences, and its role in triggering apoptosis and inhibiting inflammation, angiogenesis, and metastasis. Additionally, the review includes a thorough examination of thymoquinone's pharmacokinetics and safety, making it the first of its kind in its comprehensiveness.
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Affiliation(s)
- Bunty Sharma
- Department of Biotechnology, Graphic Era (Deemed to Be University), Dehradun, Uttarakhand, India
| | - Himanshu Shekhar
- Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bhatinda, 151001, India
| | - Anidrisha Sahu
- Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bhatinda, 151001, India
| | - Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, 45142, Jazan, Saudi Arabia
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, 1102 2801, Lebanon
| | - Damandeep Kaur
- University Centre for Research & Development, University Institute of Pharmaceutical Sciences, Chandigarh University, Gharuan, Mohali, Punjab, 140413, India
| | - Hardeep Singh Tuli
- Department of Bio-Sciences and Technology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to Be University), Mullana, Ambala, 133207, India
| | - Ujjawal Sharma
- Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bhatinda, 151001, India.
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Bday J, Souid M, Pires V, Gabbouj S, Véjux A, Lizard G, Hassen E. Arginase Activity Inhibition With Thymoquinone Induces a Hybrid Type of Cell-Death in MDA-MB-231 Cell Line. J Biochem Mol Toxicol 2025; 39:e70130. [PMID: 39829401 PMCID: PMC11744436 DOI: 10.1002/jbt.70130] [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: 08/20/2024] [Revised: 11/18/2024] [Accepted: 12/29/2024] [Indexed: 01/22/2025]
Abstract
Arginase plays a crucial role in the urea cycle; it also has immunosuppressive and pro-tumor effects. The present study aimed to assess the effects of arginase inhibition by thymoquinone (2-Isopropyl-5-methyl-1,4-benzoquinone), an active compound of Nigella sativa, on cell death in the MDA-MB-231 triple-negative breast tumor cell line. Cell viability assays, Western blot analysis, and flow cytometry analysis were used to characterize oxidative stress and cell death. Our results showed that inhibition of arginase activity with thymoquinone significantly increased intracellular nitric oxide levels and resulted in overproduction of cellular and mitochondrial reactive oxygen species. Reductions in cell viability, cycle arrest, and increased cell death were also observed. Loss of transmembrane mitochondrial potential, activation of caspase-3, -7, and -9, cleavage of PARP, condensation and/or fragmentation of the nuclei, suggest that this cell death involved apoptosis. Furthermore, a cytoplasm vacuole formation and an increase in the ratio of [LC3-II/LC3-I] suggests a concomitant activation of autophagy with apoptosis. Altogether, the present study highlighted that arginase inhibition with thymoquinone induces a hybrid type of cell death defined as oxiapoptophagy. Thus, arginase inhibition with thymoquinone in the MDA-MB-231 cell line could be, in part, involved in the anticancer effect of thymoquinone.
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Affiliation(s)
- Jaweher Bday
- Molecular Immuno‐Oncology LaboratoryUniversity of MonastirMonastirTunisia
- Higher Institute of Biotechnology of MonastirUniversity of MonastirMonastirTunisia
| | - Moufida Souid
- Molecular Immuno‐Oncology LaboratoryUniversity of MonastirMonastirTunisia
- Higher Institute of Biotechnology of MonastirUniversity of MonastirMonastirTunisia
| | - Vivien Pires
- Bio‐PeroxIL ‘Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism’ Laboratory (EA 7270)Université de Bourgogne (UB)DijonFrance
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut AgroUniversité de BourgogneDijonFrance
| | - Sallouha Gabbouj
- Molecular Immuno‐Oncology LaboratoryUniversity of MonastirMonastirTunisia
| | - Anne Véjux
- Bio‐PeroxIL ‘Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism’ Laboratory (EA 7270)Université de Bourgogne (UB)DijonFrance
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut AgroUniversité de BourgogneDijonFrance
| | - Gérard Lizard
- Bio‐PeroxIL ‘Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism’ Laboratory (EA 7270)Université de Bourgogne (UB)DijonFrance
| | - Elham Hassen
- Molecular Immuno‐Oncology LaboratoryUniversity of MonastirMonastirTunisia
- Higher Institute of Biotechnology of MonastirUniversity of MonastirMonastirTunisia
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Xu M, Feng P, Yan J, Li L. Mitochondrial quality control: a pathophysiological mechanism and potential therapeutic target for chronic obstructive pulmonary disease. Front Pharmacol 2025; 15:1474310. [PMID: 39830343 PMCID: PMC11739169 DOI: 10.3389/fphar.2024.1474310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 12/11/2024] [Indexed: 01/22/2025] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is a prevalent chronic respiratory disease worldwide. Mitochondrial quality control mechanisms encompass processes such as mitochondrial biogenesis, fusion, fission, and autophagy, which collectively maintain the quantity, morphology, and function of mitochondria, ensuring cellular energy supply and the progression of normal physiological activities. However, in COPD, due to the persistent stimulation of harmful factors such as smoking and air pollution, mitochondrial quality control mechanisms often become deregulated, leading to mitochondrial dysfunction. Mitochondrial dysfunction plays a pivotal role in the pathogenesis of COPD, contributing toinflammatory response, oxidative stress, cellular senescence. However, therapeutic strategies targeting mitochondria remain underexplored. This review highlights recent advances in mitochondrial dysfunction in COPD, focusing on the role of mitochondrial quality control mechanisms and their dysregulation in disease progression. We emphasize the significance of mitochondria in the pathophysiological processes of COPD and explore potential strategies to regulate mitochondrial quality and improve mitochondrial function through mitochondrial interventions, aiming to treat COPD effectively. Additionally, we analyze the limitations and challenges of existing therapeutic strategies, aiming to provide new insights and methods for COPD treatment.
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Affiliation(s)
- Mengjiao Xu
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Peng Feng
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Ferguson Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, United States
| | - Jun Yan
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Lei Li
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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Bakir E, Baglama SS. The Effect of Foot Reflexology and Knee Massage With Black Cumin Seed Oil on Knee Osteoarthritis Symptoms. Holist Nurs Pract 2024:00004650-990000000-00066. [PMID: 39642267 DOI: 10.1097/hnp.0000000000000714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/08/2024]
Abstract
This study aimed to examine the effect of foot reflexology and knee massage with black cumin seed oil on pain and fatigue symptoms in elderly individuals with knee osteoarthritis and assess which of these 2 applications is more effective. Our randomized controlled trial was conducted with 150 participants. Study data were collected from participants over 65 years who received outpatient treatment in a university hospital's physical therapy and rehabilitation unit and were determined to have no perception problems based on the Mini-Mental Test. After randomization, the study sample was classified into 5 groups, each including 30 participants: (1) foot reflexology with black cumin seed oil, (2) foot reflexology with a placebo, (3) knee massage with black cumin oil, (4) knee massage with a placebo, and (5) control. Participants were administered a Patient Descriptive Information Form, the Lequesne Knee Osteoarthritis Index, the Pain-Visual Analog Scale, the Fatigue Severity Scale, and the Western Ontario and McMaster Universities Osteoarthritis Index. Control group participants received standard of care, while participants in treatment groups received the studied interventions for 6 weeks. Data were collected by administering questionnaires to the participants in the first and sixth weeks and analyzed using IBM Statistical Package for Social Sciences 22.0 software. The study showed that foot reflexology and knee massage administered using black cumin oil effectively reduced pain and fatigue severity in Osteoarthritis (OA) patients, and overall, foot reflexology administered using black cumin oil was the most effective treatment to reduce pain and fatigue.
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Affiliation(s)
- Ercan Bakir
- Author Affiliations: Department of Nursing, Faculty of Health Sciences, Adıyaman University, Adıyaman, Turkiye (Dr Bakir); and Department of Nursing, Faculty of Health Sciences, Mugla Sıtkı Kocman University, Mugla, Turkiye (Dr Samancioglu Baglama)
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Gontar Ł, Geszprych A, Sitarek-Andrzejczyk M, Osińska E. Influence of Plant Phenology on Chemical Composition of Monarda fistulosa L. Organs and their Bioactive Properties. PLANT FOODS FOR HUMAN NUTRITION (DORDRECHT, NETHERLANDS) 2024; 79:920-925. [PMID: 39325328 PMCID: PMC11573850 DOI: 10.1007/s11130-024-01238-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 09/05/2024] [Indexed: 09/27/2024]
Abstract
Monarda fistulosa L. above-ground organs, collected at three phases of plant phenology, were investigated as potential raw materials for application in the food industry. They were evaluated regarding essential oil (EO) content, composition, and antimicrobial activity, as well as characteristics of phenolic fractions and antioxidant properties, which may determine health benefits and potential use in food preservation. The dominant constituent of leaf EO was carvacrol. In the inflorescence EO carvacrol content was especially high at the full flowering phase (45.12%), while during the fruit setting phase its content was lower than that of p-cymene (39.75%) and thymoquinone (25.04%). In the agar dilution test, leaf and inflorescence EOs inhibited the growth of the six tested microorganisms at the concentration range of 0.156-0.625 µL/mL. Leaves collected at the vegetative phase of plant growth were characterised by the highest content of rosmarinic acid and didymin. Inflorescences harvested during the flowering of plants were rich in linarin. Flavonoid content was highly correlated with antioxidant activity of extracts. Due to these properties, M. fistulosa extracts and essential oils could be used in the food industry as natural preservatives or antioxidants, thereby contributing to the development of safer and more sustainable food products.
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Affiliation(s)
- Łukasz Gontar
- Department of Vegetable and Medicinal Plants, Institute of Horticulture Sciences, Warsaw University of Life Sciences, 159 Nowoursynowska Street, Warsaw, 02-776, Poland.
| | - Anna Geszprych
- Department of Vegetable and Medicinal Plants, Institute of Horticulture Sciences, Warsaw University of Life Sciences, 159 Nowoursynowska Street, Warsaw, 02-776, Poland
| | - Monika Sitarek-Andrzejczyk
- Research and Innovation Centre Pro-Akademia, 9/11 Innowacyjna Street, Konstantynów Łódzki, 95-050, Poland
| | - Ewa Osińska
- Department of Vegetable and Medicinal Plants, Institute of Horticulture Sciences, Warsaw University of Life Sciences, 159 Nowoursynowska Street, Warsaw, 02-776, Poland
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Durga BB, Ramachandran V, Senthil B, Soloman VG, Elshikh MS, Almutairi SM, Wen ZH, Lo YH. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells. Open Life Sci 2024; 19:20221000. [PMID: 39655191 PMCID: PMC11627060 DOI: 10.1515/biol-2022-1000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 09/20/2024] [Accepted: 10/10/2024] [Indexed: 12/12/2024] Open
Abstract
This research examines the cytotoxic consequences of thymoquinone-loaded bovine serum albumin nanoparticles (TQ-BSA NPs) on the A549 lung cancer cell line. UV-visible (UV-Vis) spectroscopy, Fourier transform infrared spectrophotometer (FT-IR), scanning electron microscopy (SEM), and dynamic light scattering (DLS) were employed to verify the biogenic TQ-BSA NPs' size, shape, and distribution. UV-Vis spectrophotometry indicated peaks at 200-300 nm, 500-600 nm, and a prominent peak at 700-800 nm, confirming the presence of TQ-BSA NPs. The polydispersity index, as confirmed by DLS, indicated a solvent distribution in water, accompanied by a zeta potential value of 126.2 ± 46.8 mV. The average size of TQ-BSA NPs was confirmed to be 187 ± 8 nm by SEM. TQ-BSA NPs reduce colony formation in the A549 lung cancer cell line in a dose-dependent manner relative to the control group. Protein expression analysis indicated that TQ-BSA NPs promoted programmed cell death by increasing pro-apoptotic levels and decreasing anti-apoptotic levels. TQ-BSA NPs demonstrated inhibition of cancer cell proliferation and promotion of apoptosis and exhibited significant efficacy against cancer cells at low concentrations. As a result, they have the makings of a promising chemotherapeutic agent for low-dose, long-term administration.
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Affiliation(s)
- Bala Baskaran Durga
- Faculty of Allied Health Sciences, Meenakshi Academy of Higher Education & Research, Chennai, India
| | - Vinayagam Ramachandran
- Department of Biotechnology, Institute of Biotechnology, College of Life and Applied Sciences, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk, 38541, Republic of Korea
| | - Bakthavatchalam Senthil
- Department of Chemistry, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Ramapuram, Chennai, Tamil Nadu, India
| | - Vasthi Gnanarani Soloman
- Department of Chemistry, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Ramapuram, Chennai, Tamil Nadu, India
| | - Mohamed Soliman Elshikh
- Department of Botany and Microbiology, College of Science, King Saud University, P.O. 2455, Riyadh, 11451, Saudi Arabia
| | - Saeedah Musaed Almutairi
- Department of Botany and Microbiology, College of Science, King Saud University, P.O. 2455, Riyadh, 11451, Saudi Arabia
| | - Zhi-Hong Wen
- Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, 80424, Taiwan
- Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung, 804201, Taiwan
| | - Yi-Hao Lo
- Department of Family Medicine, Zuoying Armed Forces General Hospital, Kaohsiung, 81342, Taiwan
- Department of Nursing, Meiho University, Pingtung County91200, Taiwan
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Singh A, Mishra A, Meena A, Mishra N, Luqman S. Exploration of selected monoterpenes as potential TRPC channel family modulator in lung cancer, an in-silico upshot. J Biomol Struct Dyn 2024; 42:7917-7933. [PMID: 37526232 DOI: 10.1080/07391102.2023.2241900] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 07/24/2023] [Indexed: 08/02/2023]
Abstract
Lung cancer is still the most frequent cause of cancer-related death, accounting for nearly two million cases yearly. As cancer is a multifactorial disease, developing novel molecular therapeutics that can simultaneously target multiple associated cellular processes has become necessary. Ion channels are diverse regulators of cancer-related processes such as abnormal proliferation, invasion, migration, tumor progression, inhibition of apoptosis, and chemoresistance. Among the various families of ion channels, the transient receptor potential canonical channel family steps out in the context of lung cancer, as several members have been postulated as prognostic markers for lung cancer. Phytochemicals have been found to have health benefits in the treatment of a variety of diseases and disorders. Among phytochemicals, monoterpenes are effective in treating both the early and late stages of cancer. The molecular docking interaction analysis was conducted to evaluate the binding potential of selected monoterpenes with TRPC3, TRPC4, TRPC5, and TRPC6 involved in different phases of carcinogenesis. Amongst the selected monoterpenes, thymoquinone exhibited the highest binding energy of -6.7 kcal/mol against the TRPC4 channel, and all amino acid binding residues were similar to those of the known inhibitor for TRPC4. In addition, molecular-dynamic simulation results parameters, such as RMSD, RMSF, and Rg, indicated that thymoquinone did not impact the protein compactness and exhibited stability during the interaction. The average interaction energy between thymoquinone and TRPC4 protein was -26.85 kJ/mol. In-silico Drug-likeness and ADMET profiling indicated that thymoquinone is a druggable candidate with minimal toxicity. We propose further investigation and evaluation of thymoquinone for lead optimization and drug development.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Akanksha Singh
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, Uttar Pradesh, India
| | - Anamika Mishra
- Department of Applied Sciences, Indian Institute of Information Technology Allahabad, Prayagraj, Uttar Pradesh, India
| | - Abha Meena
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, Uttar Pradesh, India
- Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
| | - Nidhi Mishra
- Department of Applied Sciences, Indian Institute of Information Technology Allahabad, Prayagraj, Uttar Pradesh, India
| | - Suaib Luqman
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, Uttar Pradesh, India
- Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
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Talib WH, Abed I, Raad D, Alomari RK, Jamal A, Jabbar R, Alhasan EOA, Alshaeri HK, Alasmari MM, Law D. Targeting Cancer Hallmarks Using Selected Food Bioactive Compounds: Potentials for Preventive and Therapeutic Strategies. Foods 2024; 13:2687. [PMID: 39272454 PMCID: PMC11395675 DOI: 10.3390/foods13172687] [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: 06/30/2024] [Revised: 08/23/2024] [Accepted: 08/23/2024] [Indexed: 09/15/2024] Open
Abstract
Cancer continues to be a prominent issue in healthcare systems, resulting in approximately 9.9 million fatalities in 2020. It is the second most common cause of death after cardiovascular diseases. Although there are difficulties in treating cancer at both the genetic and phenotypic levels, many cancer patients seek supplementary and alternative medicines to cope with their illness, relieve symptoms, and reduce the side effects of cytotoxic drug therapy. Consequently, there is an increasing emphasis on studying natural products that have the potential to prevent or treat cancer. Cancer cells depend on multiple hallmarks to secure survival. These hallmarks include sustained proliferation, apoptosis inactivation, stimulation of angiogenesis, immune evasion, and altered metabolism. Several natural products from food were reported to target multiple cancer hallmarks and can be used as adjuvant interventions to augment conventional therapies. This review summarizes the main active ingredients in food that have anticancer activities with a comprehensive discussion of the mechanisms of action. Thymoquinone, allicin, resveratrol, parthenolide, Epigallocatechin gallate, and piperine are promising anticancer bioactive ingredients in food. Natural products discussed in this review provide a solid ground for researchers to provide effective anticancer functional food.
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Affiliation(s)
- Wamidh H Talib
- Faculty of Allied Medical Sciences, Applied Science Private University, Amman 11931, Jordan
- Faculty of Health and Life Sciences, Inti International University, Nilai 71800, Negeri Sembilan, Malaysia
| | - Ilia Abed
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Daniah Raad
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Raghad K Alomari
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Ayah Jamal
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Rand Jabbar
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Eman Omar Amin Alhasan
- Faculty of Allied Medical Sciences, Applied Science Private University, Amman 11931, Jordan
| | - Heba K Alshaeri
- Department of Pharmacology, Faculty of Medicine, King Abdul-Aziz University, Rabigh 25724, Saudi Arabia
| | - Moudi M Alasmari
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Jeddah 21423, Saudi Arabia
- King Abdullah International Medical Research Centre (KAIMRC), Jeddah 22233, Saudi Arabia
| | - Douglas Law
- Faculty of Health and Life Sciences, Inti International University, Nilai 71800, Negeri Sembilan, Malaysia
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12
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Eloraby DAI, El-Gayar SF, El-Bolok AH, Ammar SG, ElShafei MM. In Vitro Assessment of the Cytotoxic Effect of 5-Fluorouracil, Thymoquinone and their Combination on Tongue Squamous Cell Carcinoma Cell Line. Asian Pac J Cancer Prev 2024; 25:2169-2176. [PMID: 38918680 PMCID: PMC11382834 DOI: 10.31557/apjcp.2024.25.6.2169] [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: 02/23/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Tongue cancer is the most prevalent type of oral cancer. Recently, natural compounds have been considered important resources for several anticancer drugs. Thymoquinone (TQ) exhibits a potent anti-cancer effect. 5-Fluorouracil (5-FU) is a chemotherapeutic drug that has been utilized in the treatment of cancer. Recently, combination therapy has gained popularity as a treatment option for patients with cancer. OBJECTIVES The present study was carried out to assess the cytotoxic effect of 5-Fluorouracil (5-FU), Thymoquinone (TQ), and their combination on tongue squamous cell carcinoma cell line (HNO-97). METHODS Tongue carcinoma cell line (HNO-97) was maintained in cultured flasks and the cells were divided into four groups; group Ι: control untreated group, group ΙΙ: HNO-97-treated cells with different concentrations of 5-FU from 0.5 µM/ml to 3µM/ml, group ΙIΙ: HNO-97-treated cells with different concentrations of TQ from 7.25µM/ml to 23.05µM/ml, and group ΙV: HNO-97-treated cells with both 5-FU and TQ in serial concentrations till (IC50) in a dose of 27.44 µM/ml. Determination of the cytotoxic effect of the tested agents on the HNO-97 cell line was done using methyl thiazole tetrazolium assay, nuclear morphometric analysis, microscopic examination, and annexin-v/ propidium iodide staining assay. RESULT The findings revealed that the cytotoxic effect of 5-FU, TQ, and their combination on tongue squamous cell carcinoma cell line (HNO-97) was dose-dependent. The microscopic examination revealed that 5-FU, TQ alone, or their combination induced apoptotic cell death. P-value < 0.05 was statistically significant. CONCLUSION The combination of 5-FU and TQ produced a marked cytotoxic effect on HNO-97 cells.
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Affiliation(s)
- Dina Ashraf Ibrahim Eloraby
- Oral and Maxillofacial Pathology Department, Faculty of Dentistry, Minia University, Minia 61519, Egypt
- Oral and Maxillofacial Pathology Department, Faculty of oral and Dental Medicine, Misr International University, Obour 19648, Egypt
| | - Sherif Farouk El-Gayar
- Oral and Maxillofacial Pathology Department, Faculty of Dentistry, Minia University, Minia 61519, Egypt
| | - Amr Helmy El-Bolok
- Oral and Maxillofacial Pathology Department, Faculty of Dentistry, Minia University, Minia 61519, Egypt
| | - Sabreen Gamal Ammar
- Oral and Maxillofacial Pathology Department, Faculty of Dentistry, Minia University, Minia 61519, Egypt
| | - Marwa Mokbel ElShafei
- Oral and Maxillofacial Pathology Department, Faculty of oral and Dental Medicine, Misr International University, Obour 19648, Egypt
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13
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Masood M, Singh P, Hariss D, Khan F, Yameen D, Siraj S, Islam A, Dohare R, Mahfuzul Haque M. Nitric oxide as a double-edged sword in pulmonary viral infections: Mechanistic insights and potential therapeutic implications. Gene 2024; 899:148148. [PMID: 38191100 DOI: 10.1016/j.gene.2024.148148] [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: 09/19/2023] [Revised: 12/21/2023] [Accepted: 01/05/2024] [Indexed: 01/10/2024]
Abstract
In the face of the global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), researchers are tirelessly exploring novel therapeutic approaches to combat coronavirus disease 2019 (COVID-19) and its associated complications. Nitric oxide (NO) has appeared as a multifaceted signaling mediator with diverse and often contrasting biological activities. Its intricate biochemistry renders it a crucial regulator of cardiovascular and pulmonary functions, immunity, and neurotransmission. Perturbations in NO production, whether excessive or insufficient, contribute to the pathogenesis of various diseases, encompassing cardiovascular disease, pulmonary hypertension, asthma, diabetes, and cancer. Recent investigations have unveiled the potential of NO donors to impede SARS-CoV- 2 replication, while inhaled NO demonstrates promise as a therapeutic avenue for improving oxygenation in COVID-19-related hypoxic pulmonary conditions. Interestingly, NO's association with the inflammatory response in asthma suggests a potential protective role against SARS-CoV-2 infection. Furthermore, compelling evidence indicates the benefits of inhaled NO in optimizing ventilation-perfusion ratios and mitigating the need for mechanical ventilation in COVID-19 patients. In this review, we delve into the molecular targets of NO, its utility as a diagnostic marker, the mechanisms underlying its action in COVID-19, and the potential of inhaled NO as a therapeutic intervention against viral infections. The topmost significant pathway, gene ontology (GO)-biological process (BP), GO-molecular function (MF) and GO-cellular compartment (CC) terms associated with Nitric Oxide Synthase (NOS)1, NOS2, NOS3 were arginine biosynthesis (p-value = 1.15 x 10-9) regulation of guanylate cyclase activity (p-value = 7.5 x 10-12), arginine binding (p-value = 2.62 x 10-11), vesicle membrane (p-value = 3.93 x 10-8). Transcriptomics analysis further validates the significant presence of NOS1, NOS2, NOS3 in independent COVID-19 and pulmonary hypertension cohorts with respect to controls. This review investigates NO's molecular targets, diagnostic potentials, and therapeutic role in COVID-19, employing bioinformatics to identify key pathways and NOS isoforms' significance.
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Affiliation(s)
- Mohammad Masood
- Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India.
| | - Prithvi Singh
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.
| | - Daaniyaal Hariss
- Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India.
| | - Faizya Khan
- Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India.
| | - Daraksha Yameen
- Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India.
| | - Seerat Siraj
- Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India.
| | - Asimul Islam
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.
| | - Ravins Dohare
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.
| | - Mohammad Mahfuzul Haque
- Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India.
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Ramineedu K, Sankaran KR, Mallepogu V, Rendedula DP, Gunturu R, Gandham S, Md SI, Meriga B. Thymoquinone mitigates obesity and diabetic parameters through regulation of major adipokines, key lipid metabolizing enzymes and AMPK/p-AMPK in diet-induced obese rats. 3 Biotech 2024; 14:16. [PMID: 38125651 PMCID: PMC10728404 DOI: 10.1007/s13205-023-03847-x] [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: 09/16/2023] [Accepted: 11/02/2023] [Indexed: 12/23/2023] Open
Abstract
UNLABELLED The present study was designed to evaluate the anti-obesity and anti-hyperglycemic activity of Thymoquinone (ThyQ) isolated from Nigella sativa seeds. Male Wistar rats were randomly divided into five groups and fed either normal pellet diet or high-fat diet (HFD) for 18 weeks and water ad-libitum. Group I: normal pellet diet (NPD)-fed, Group II: high-fat diet (HFD)-fed, Group III: HFD-fed-ThyQ (20 mg)-treated, Group IV: HFD-fed-ThyQ (40 mg)-treated and Group V: HFD-fed-Orlistat (5 mg)-treated group. Intervention with ThyQ started from 12th week onwards to HFD-fed rats of group III and IV. ThyQ administration significantly (p < 0.01) mitigated body weight gain, blood glucose, insulin level, serum and liver lipids (except HDL) and improved glucose tolerance and insulin sensitivity as evaluated by oral glucose tolerance test (OGTT), homeostasis model assessment-insulin resistance (HOMA-IR) and insulin tolerance test (ITT). Furthermore, ThyQ significantly (p < 0.01) diminished serum aspartate transaminase (AST), alanine transaminase (ALT), acetyl-CoA carboxylase (ACC), plasma leptin, resistin and visfatin levels but enhanced lipoprotein lipase (LPL) and adiponectin levels. RT-PCR analysis demonstrated down-regulated mRNA expression of sterol regulatory element-binding proteins-1c (SREBP-1c), CCAAT/enhancer-binding protein-α (C/EBP-α) and fatty acid synthase (FAS) but upregulation of Insulin receptor substrate-1 (IRS-1).Western blot analysis displayed phosphorylation of adenosine monophosphate activated protein kinase (AMPK) in ThyQ-treated rats. Liver microtome sections of HFD-fed rats showed degenerated hepatocytes with high lipid stores while that of adipose tissue sections displayed large, fat-laden adipocytes, however, these histological changes were considerably attenuated in ThyQ-treated groups. Together these findings demonstrate that ThyQ can be a valuable therapeutic compound to potentially alleviate diet-induced obesity, hyperglycemia and insulin resistance. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s13205-023-03847-x.
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Affiliation(s)
- Keerthi Ramineedu
- Division of Cell Culture and Molecular Biology, Department of Biochemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh 517502 India
| | - Karunakaran Reddy Sankaran
- Division of Cell Culture and Molecular Biology, Department of Biochemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh 517502 India
| | - Venkataswamy Mallepogu
- Division of Cell Culture and Molecular Biology, Department of Biochemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh 517502 India
| | | | | | - Sreedevi Gandham
- Department of ECE, Siddartha Educational Academy Group of Institutions, Tirupati, AP 517502 India
| | - Shahidul Islam Md
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000 South Africa
| | - Balaji Meriga
- Division of Cell Culture and Molecular Biology, Department of Biochemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh 517502 India
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15
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Ibrahim KG, Hudu SA, Jega AY, Taha A, Yusuf AP, Usman D, Adeshina KA, Umar ZU, Nyakudya TT, Erlwanger KH. Thymoquinone: A comprehensive review of its potential role as a monotherapy for metabolic syndrome. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2024; 27:1214-1227. [PMID: 39229585 PMCID: PMC11366942 DOI: 10.22038/ijbms.2024.77203.16693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Accepted: 04/06/2024] [Indexed: 09/05/2024]
Abstract
Metabolic syndrome (MetS) is a widespread global epidemic that affects individuals across all age groups and presents a significant public health challenge. Comprising various cardio-metabolic risk factors, MetS contributes to morbidity and, when inadequately addressed, can lead to mortality. Current therapeutic approaches involve lifestyle changes and the prolonged use of pharmacological agents targeting the individual components of MetS, posing challenges related to cost, compliance with medications, and cumulative side effects. To overcome the challenges associated with these conventional treatments, herbal medicines and phytochemicals have been explored and proven to be holistic complements/alternatives in the management of MetS. Thymoquinone (TQ), a prominent bicyclic aromatic compound derived from Nigella sativa emerges as a promising candidate that has demonstrated beneficial effects in the treatment of the different components of MetS, with a good safety profile. For methodology, literature searches were conducted using PubMed and Google Scholar for relevant studies until December 2023. Using Boolean Operators, TQ and the individual components of MetS were queried against the databases. The retrieved articles were screened for eligibility. As a result, we provide a comprehensive overview of the anti-obesity, anti-dyslipidaemic, anti-hypertensive, and anti-diabetic effects of TQ including some underlying mechanisms of action such as modulating the expression of several metabolic target genes to promote metabolic health. The review advocates for a paradigm shift in MetS management, it contributes valuable insights into the multifaceted aspects of the application of TQ, fostering an understanding of its role in mitigating the global burden of MetS.
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Affiliation(s)
- Kasimu Ghandi Ibrahim
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, P.O. Box 2000, Zarqa 13110, Jordan
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto P.M.B 2346, Nigeria
| | - Shuaibu Abdullahi Hudu
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, P.O. Box 2000, Zarqa 13110, Jordan
- Department of Medical Microbiology and Immunology, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo
| | | | - Ahmad Taha
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, P.O. Box 2000, Zarqa 13110, Jordan
- Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, P.M.B. 2254
| | | | - Dawoud Usman
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto P.M.B 2346, Nigeria
- Department of Physiology, Faculty of Medicine, Port-said University, Egypt
| | - Kehinde Ahmad Adeshina
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto P.M.B 2346, Nigeria
- Department of Biochemistry, Federal University of Technology, P.M.B. 65, Minna, Niger State, Nigeria
| | - Zayyanu Usman Umar
- Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto P.M.B 2346, Nigeria
| | - Trevor Tapiwa Nyakudya
- Biomedical Science Research and Training Centre (BioRTC), Yobe State University, Damaturu, Nigeria
| | - Kennedy Honey Erlwanger
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa
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16
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Lv M, Ding Y, Zhang Y, Liu S. Targeting EBV-encoded products: Implications for drug development in EBV-associated diseases. Rev Med Virol 2024; 34:e2487. [PMID: 37905912 DOI: 10.1002/rmv.2487] [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: 08/09/2023] [Revised: 10/02/2023] [Accepted: 10/22/2023] [Indexed: 11/02/2023]
Abstract
Epstein-Barr virus, a human gamma-herpesvirus, has a close connection to the pathogenesis of cancers and other diseases, which are a burden for public health worldwide. So far, several drugs or biomolecules have been discovered that can target EBV-encoded products for treatment, such as Silvestrol, affinity toxin, roscovitine, H20, H31, curcumin, thymoquinone, and ribosomal protein L22. These drugs activate or inhibit the function of some biomolecules, affecting subsequent signalling pathways by acting on the products of EBV. These drugs usually target LMP1, LMP2; EBNA1, EBNA2, EBNA3; EBER1, EBER2; Bam-HI A rightward transcript and BHRF1. Additionally, some promising findings in the fields of vaccines, immunological, and cellular therapies have been established. In this review, we mainly summarise the function of drugs mentioned above and unique mechanisms, hoping that we can help giving insight to the design of drugs for the treatment of EBV-associated diseases.
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Affiliation(s)
- Mengwen Lv
- Department of Blood Transfusion, The Affiliated Hospital of Qingdao University, Qingdao, China
- Department of Pathogenic Biology, Qingdao University Medical College, Qingdao, China
| | - Yuan Ding
- Department of Special Examination, Qingdao Women & Children Hospital, Qingdao, China
| | - Yan Zhang
- Department of Pathogenic Biology, Qingdao University Medical College, Qingdao, China
- Department of Clinical Laboratory, Zibo Central Hospital, Zibo, China
| | - Shuzhen Liu
- Department of Blood Transfusion, The Affiliated Hospital of Qingdao University, Qingdao, China
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17
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Kurowska N, Madej M, Strzalka-Mrozik B. Thymoquinone: A Promising Therapeutic Agent for the Treatment of Colorectal Cancer. Curr Issues Mol Biol 2023; 46:121-139. [PMID: 38248312 PMCID: PMC10814900 DOI: 10.3390/cimb46010010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 12/18/2023] [Accepted: 12/21/2023] [Indexed: 01/23/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and is responsible for approximately one million deaths each year. The current standard of care is surgical resection of the lesion and chemotherapy with 5-fluorouracil (5-FU). However, of concern is the increasing incidence in an increasingly younger patient population and the ability of CRC cells to develop resistance to 5-FU. In this review, we discuss the effects of thymoquinone (TQ), one of the main bioactive components of Nigella sativa seeds, on CRC, with a particular focus on the use of TQ in combination therapy with other chemotherapeutic agents. TQ exhibits anti-CRC activity by inducing a proapoptotic effect and inhibiting proliferation, primarily through its effect on the regulation of signaling pathways crucial for tumor progression and oxidative stress. TQ can be used synergistically with chemotherapeutic agents to enhance their anticancer effects and to influence the expression of signaling pathways and other genes important in cancer development. These data appear to be most relevant for co-treatment with 5-FU. We believe that TQ is a suitable candidate for consideration in the chemoprevention and adjuvant therapy for CRC, but further studies, including clinical trials, are needed to confirm its safety and efficacy in the treatment of cancer.
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Affiliation(s)
- Natalia Kurowska
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland; (N.K.); (M.M.)
| | - Marcel Madej
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland; (N.K.); (M.M.)
- Silesia LabMed, Centre for Research and Implementation, Medical University of Silesia, 40-752 Katowice, Poland
| | - Barbara Strzalka-Mrozik
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland; (N.K.); (M.M.)
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18
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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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19
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Roohi TF, Faizan S, Parray ZA, Baig MDAI, Mehdi S, Kinattingal N, Krishna KL. Beyond Glucose: The Dual Assault of Oxidative and ER Stress in Diabetic Disorders. High Blood Press Cardiovasc Prev 2023; 30:513-531. [PMID: 38041772 DOI: 10.1007/s40292-023-00611-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 11/15/2023] [Indexed: 12/03/2023] Open
Abstract
Diabetes mellitus, a prevalent global health concern, is characterized by hyperglycemia. However, recent research reveals a more intricate landscape where oxidative stress and endoplasmic reticulum (ER) stress orchestrate a dual assault, profoundly impacting diabetic disorders. This review elucidates the interplay between these two stress pathways and their collective consequences on diabetes. Oxidative stress emanates from mitochondria, where reactive oxygen species (ROS) production spirals out of control, leading to cellular damage. We explore ROS-mediated signaling pathways, which trigger β-cell dysfunction, insulin resistance, and endothelial dysfunction the quintessential features of diabetes. Simultaneously, ER stress unravels, unveiling how protein folding disturbances activate the unfolded protein response (UPR). We dissect the UPR's dual role, oscillating between cellular adaptation and apoptosis, significantly influencing pancreatic β-cells and peripheral insulin-sensitive tissues. Crucially, this review exposes the synergy between oxidative and ER stress pathways. ROS-induced UPR activation and ER stress-induced oxidative stress create a detrimental feedback loop, exacerbating diabetic complications. Moreover, we spotlight promising therapeutic strategies that target both stress pathways. Antioxidants, molecular chaperones, and novel pharmacological agents offer potential avenues for diabetes management. As the global diabetes burden escalates, comprehending the dual assault of oxidative and ER stress is paramount. This review not only unveils the intricate molecular mechanisms governing diabetic pathophysiology but also advocates a holistic therapeutic approach. By addressing both stress pathways concurrently, we may forge innovative solutions for diabetic disorders, ultimately alleviating the burden of this pervasive health issue.
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Affiliation(s)
- Tamsheel Fatima Roohi
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore, Karnataka, 570015, India
| | - Syed Faizan
- Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore, Karnataka, 570015, India
| | - Zahoor Ahmad Parray
- Department of Chemistry, Indian Institute of Technology (IIT) Delhi, Hauz Khas Campus, New Delhi, 110016, India
| | - M D Awaise Iqbal Baig
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore, Karnataka, 570015, India
| | - Seema Mehdi
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore, Karnataka, 570015, India
| | - Nabeel Kinattingal
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore, Karnataka, 570015, India
| | - K L Krishna
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore, Karnataka, 570015, India.
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20
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Shaukat A, Zaidi A, Anwar H, Kizilbash N. Mechanism of the antidiabetic action of Nigella sativa and Thymoquinone: a review. Front Nutr 2023; 10:1126272. [PMID: 37818339 PMCID: PMC10561288 DOI: 10.3389/fnut.2023.1126272] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Accepted: 07/27/2023] [Indexed: 10/12/2023] Open
Abstract
Introduction Long used in traditional medicine, Nigella sativa (NS; Ranunculaceae) has shown significant efficacy as an adjuvant therapy for diabetes mellitus (DM) management by improving glucose tolerance, decreasing hepatic gluconeogenesis, normalizing blood sugar and lipid imbalance, and stimulating insulin secretion from pancreatic cells. In this review, the pharmacological and pharmacokinetic properties of NS as a herbal diabetes medication are examined in depth, demonstrating how it counteracts oxidative stress and the onset and progression of DM. Methods This literature review drew on databases such as Google Scholar and PubMed and various gray literature sources using search terms like the etiology of diabetes, conventional versus herbal therapy, subclinical pharmacology, pharmacokinetics, physiology, behavior, and clinical outcomes. Results The efficiency and safety of NS in diabetes, notably its thymoquinone (TQ) rich volatile oil, have drawn great attention from researchers in recent years; the specific therapeutic dose has eluded determination so far. TQ has anti-diabetic, anti-inflammatory, antioxidant, and immunomodulatory properties but has not proved druggable. DM's intimate link with oxidative stress, makes NS therapy relevant since it is a potent antioxidant that energizes the cell's endogenous arsenal of antioxidant enzymes. NS attenuates insulin resistance, enhances insulin signaling, suppresses cyclooxygenase-2, upregulates insulin-like growth factor-1, and prevents endothelial dysfunction in DM. Conclusion The interaction of NS with mainstream drugs, gut microbiota, and probiotics opens new possibilities for innovative therapies. Despite its strong potential to treat DM, NS and TQ must be examined in more inclusive clinical studies targeting underrepresented patient populations.
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Affiliation(s)
- Arslan Shaukat
- Department of Physiology, Government College University - GCU, Faisalabad, Punjab, Pakistan
| | - Arsalan Zaidi
- National Probiotic Laboratory, National Institute for Biotechnology and Genetic Engineering College - NIBGE-C, Faisalabad, Punjab, Pakistan
- Pakistan Institute of Engineering and Applied Sciences - PIEAS, Nilore, Islamabad, Pakistan
| | - Haseeb Anwar
- Department of Physiology, Government College University - GCU, Faisalabad, Punjab, Pakistan
| | - Nadeem Kizilbash
- Department Medical Laboratory Technology, Faculty of Applied Medical Sciences, Northern Border University, Arar, Saudi Arabia
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Das S, Ghosh A, Upadhyay P, Sarker S, Bhattacharjee M, Gupta P, Chattopadhyay S, Ghosh S, Dhar P, Adhikary A. A mechanistic insight into the potential anti-cancerous property of Nigella sativa on breast cancer through micro-RNA regulation: An in vitro & in vivo study. Fitoterapia 2023; 169:105601. [PMID: 37406886 DOI: 10.1016/j.fitote.2023.105601] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 06/29/2023] [Accepted: 06/30/2023] [Indexed: 07/07/2023]
Abstract
Cancer continues to threat mortal alongside scientific community with burgeoning grasp. Most efforts directed to tame Cancer such as radiotherapy or chemotherapy, all came at a cost of severe side effects. The plant derived bioactive compounds on the other hand carries an inevitable advantage of being safer, bioavailable & less toxic compared to contemporary chemotherapeutics. Our strategic approach employed solvent extraction of Black Seed Oil (BSO) to highlight the orchestrated use of its oil soluble phytochemicals - Thymoquinone, Carvacrol & Trans-Anethole when used in cohort. These anti-cancer agents in unbelievably modest amounts present in BSO shows better potential to delineate migratory properties in breast cancer cells as compared to when treated individually. BSO was also observed to have apoptotic calibre when investigated in MDA-MB-231 and MCF-7 cell lines. We performed chemical characterization of the individual phytochemical as well as the oil in-whole to demonstrate the bioactive oil-soluble entities present in whole extract. BSO was observed to have significant anti-cancerous properties in cumulative proportion that is reportedly higher than the individual three components. Besides, this study also reports micro-RNA regulation on BSO administration, thereby playing a pivotal role in breast cancer alleviation. Thus, synergistic action of the integrants serves better combat force against breast cancer in the form of whole extract, hence aiming at a more lucrative paradigm while significantly regulating microRNAs associated with breast cancer migration and apoptosis.
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Affiliation(s)
- Shaswati Das
- Centre for Research in Nanoscience and Nanotechnology, Technology Campus, University of Calcutta, JD-2, Sector III, Salt Lake City, Kolkata 700106, India
| | - Avijit Ghosh
- Centre for Research in Nanoscience and Nanotechnology, Technology Campus, University of Calcutta, JD-2, Sector III, Salt Lake City, Kolkata 700106, India
| | - Priyanka Upadhyay
- Centre for Research in Nanoscience and Nanotechnology, Technology Campus, University of Calcutta, JD-2, Sector III, Salt Lake City, Kolkata 700106, India
| | - Sushmita Sarker
- Centre for Research in Nanoscience and Nanotechnology, Technology Campus, University of Calcutta, JD-2, Sector III, Salt Lake City, Kolkata 700106, India
| | - Mousumi Bhattacharjee
- Centre for Research in Nanoscience and Nanotechnology, Technology Campus, University of Calcutta, JD-2, Sector III, Salt Lake City, Kolkata 700106, India
| | - Payal Gupta
- Department of Physiology, University of Calcutta, 92 Acharya Prafulla Chandra Road, Kolkata 700009, WB, India
| | - Sreya Chattopadhyay
- Department of Physiology, University of Calcutta, 92 Acharya Prafulla Chandra Road, Kolkata 700009, WB, India
| | - Swatilekha Ghosh
- Amity Institute of Biotechnology, Amity University, Kolkata, Major Arterial Road (South-East), Action Area II, Newtown, Kolkata, West Bengal 700135, India
| | - Pubali Dhar
- Laboratory of Food Science and Technology, Food and Nutrition, Department of Home Science, University of Calcutta, 20, B Judges Court Road, Kolkata 700027 University, India
| | - Arghya Adhikary
- Department of Life science & Biotechnology, Jadavpur University, 188, Raja Subodh Chandra Mallick Rd, Jadavpur, Kolkata, West Bengal 700032, WB, India.
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Kwan K, Han AY, Mukdad L, Barragan F, Selim O, Alhiyari Y, St. John M. Anticancer effects of thymoquinone in head and neck squamous cell carcinoma: A scoping review. Laryngoscope Investig Otolaryngol 2023; 8:876-885. [PMID: 37731860 PMCID: PMC10508265 DOI: 10.1002/lio2.1097] [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: 01/10/2023] [Revised: 04/12/2023] [Accepted: 05/16/2023] [Indexed: 09/22/2023] Open
Abstract
Objective Thymoquinone (TQ), the active constituent of Nigella sativa, has been shown to have anticancer effects in head and neck squamous cell carcinoma (HNSCC). This review aims to outline the properties of TQ, the known drivers in HNSCC formation, and summarize the anticancer effects of TQ in SCC. Data Sources Three databases (PubMed, Embase, and Google Scholar) were queried for the key words "thymoquinone squamous cell carcinoma." Review Methods Publications that were not original research and publications that did not have full-text available for review were excluded. Results Sixteen research articles met the inclusion criteria. Our review demonstrates that TQ-induced cytotoxicity is associated with increased expression and activity of the tumor suppressor p53, proapoptotic proteins Bax and caspases, as well as decreased expression and activity of antiapoptotic proteins Bcl-2 and Mdm2. Additionally, TQ modulates cell-survival pathways such as the PI3k/Akt pathway. TQ synergizes with therapeutics including cisplatin and radiation. Early TQ administration may prevent carcinogenesis via upregulation of antioxidant enzymes, and TQ administration in the presence of cancer can result in disease mitigation via induction of oxidative stress. Conclusion TQ acts as an upregulator of proapoptotic pathways and downregulator of antiapoptotic pathways, modulates the oxidative stress balance in tumor development, and works synergistically alongside other chemotherapeutics to increase cytotoxicity. TQ has the potential to prevent carcinogenesis in patients who are at high-risk for SCC and adjuvant treatment for SCC patients undergoing conventional treatments. Future studies should aim to identify specific populations in which TQ's effects would be the most beneficial. Level of Evidence Not available.
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Affiliation(s)
- Kera Kwan
- UCLA Department of SurgeryUniversity of California Los AngelesCaliforniaLos AngelesUSA
| | - Albert Y. Han
- Department of Head and Neck SurgeryUniversity of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Laith Mukdad
- UCLA Head and Neck Cancer SurgeryUniversity of California Los AngelesCaliforniaLos AngelesUSA
| | - Frida Barragan
- UCLA Head and Neck Cancer SurgeryUniversity of California Los AngelesCaliforniaLos AngelesUSA
| | - Omar Selim
- UCLA Head and Neck Cancer SurgeryUniversity of California Los AngelesCaliforniaLos AngelesUSA
| | - Yazeed Alhiyari
- UCLA Head and Neck Cancer SurgeryUniversity of California Los AngelesCaliforniaLos AngelesUSA
| | - Maie St. John
- UCLA Head and Neck Cancer SurgeryUniversity of California Los AngelesCaliforniaLos AngelesUSA
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Li T, Tan Q, Wei C, Zou H, Liu X, Mei Z, Zhang P, Cheng J, Fu J. Design, Synthesis, and Acute Toxicity Assays for Novel Thymoquinone Derivative TQFL12 in Mice and the Mechanism of Resistance to Toxicity. Molecules 2023; 28:5149. [PMID: 37446810 DOI: 10.3390/molecules28135149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 06/26/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
TQFL12 is a novel derivative designed and synthesized on the basis of Thymoquinone (TQ) which is extracted from Nigella sativa seeds. We have demonstrated that TQFL12 was more effective in the treatment of TNBC than TQ. In order to directly reflect the acute toxicity of TQFL12 in vivo, in this study, we designed, synthesized, and compared it with TQ. The mice were administered drugs with different concentration gradients intraperitoneally, and death was observed within one week. The 24 h median lethal dose (LD50) of TQ was calculated to be 33.758 mg/kg, while that of TQFL12 on the 7th day was 81.405 mg/kg, and the toxicity was significantly lower than that of TQ. The liver and kidney tissues of the dead mice were observed by H&E staining. The kidneys of the TQ group had more severe renal damage, while the degree of the changes in the TQFL12 group was obviously less than that in the TQ group. Western blotting results showed that the expressions of phosphorylated levels of adenylate-activated protein kinase AMPKα were significantly up-regulated in the kidneys of the TQFL12 group. Therefore, it can be concluded that the acute toxicity of TQFL12 in vivo is significantly lower than that of TQ, and its anti-toxicity mechanism may be carried out through the AMPK signaling pathway, which has a good prospect for drug development.
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Affiliation(s)
- Ting Li
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
- Basic Medical School, Southwest Medical University, Luzhou 646000, China
| | - Qi Tan
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
- Basic Medical School, Southwest Medical University, Luzhou 646000, China
| | - Chunli Wei
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
| | - Hui Zou
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410013, China
| | - Xiaoyan Liu
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
| | - Zhiqiang Mei
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
| | - Pengfei Zhang
- NHC Key Laboratory of Cancer Proteomics, Department of Oncology, Central South University, Changsha 410008, China
| | - Jingliang Cheng
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
| | - Junjiang Fu
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
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M.sofiullah SS, Murugan DD, Muid SA, Wu YS, Zamakshshari NH, Quan FG, Patrick M, Choy KW. Thymoquinone reverses homocysteine-induced endothelial dysfunction via inhibition of ER-stress induced oxidative stress pathway.. [DOI: 10.21203/rs.3.rs-2964177/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
Abstract
Abstract
Hyperhomocysteinemia has been linked to an increased risk of cardiovascular diseases. High levels of homocysteine (Hcy) promote endoplasmic reticulum (ER) stress that can increase reactive oxygen species (ROS), leading to endothelial dysfunction. Thymoquinone (TQ) is the major active ingredient in Nigella sativa seeds volatile oil and is shown to have a cardioprotective effect. However, no study evaluated the effect of TQ against Hcy-induced endothelial dysfunction. Thus, this study aims to investigate the effects and mechanisms of TQ in reversing Hcy-induced endothelial dysfunction. Isolated aorta from male Sprague-Dawley (SD) rats incubated with Hcy (500 µM) and co-treated with or without TQ (0.1 µM, 1 µM, and 10 µM), 20 µM TUDCA, 100 µM Apocynin or 1 mM Tempol in organ bath to study the vascular function. Additionally, human umbilical vein endothelial cells (HUVECs) were incubated with Hcy (10 mM) and various concentrations of TQ (1 and 10 𝜇M), Tempol (100 𝜇M), Apocynin (100 𝜇M), TUDCA (100 𝜇M) or H2O2 (0.25 mM) to evaluate the cell viability by using a phase contrast microscope and dye exclusion assay. Involvement of ER stress pathway, ROS and NO bioavailability were accessed via immunoassay and fluorescent staining respectively. Molecular docking was performed to evaluate the binding affinity of TQ to GRP78. Our results revealed that Hcy impaired endothelium-dependant relaxation in isolated aorta and induced apoptosis in HUVECs. These effects were reversed by TQ, TUDCA, tempol and apocynin. Treatment with TQ (10𝜇M) also reduced ROS level, improved NO bioavailability as well reduced GRP78 and NOX4 protein in HUVECs. Result from the molecular docking study showed that TQ could bind well to GRP78 through hydrogen bond and hydrophobic interaction with the amino acid at GRP78 ATP binding pocket. Taken together, the present results suggest that TQ preserved endothelial function in rat aorta and reduced apoptosis of HUVECs induced by Hcy through the inhibition of ER stress-mediated ROS and eNOS uncoupling.
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Eid EEM, Almaiman AA, Alshehade SA, Alsalemi W, Kamran S, Suliman FO, Alshawsh MA. Characterization of Thymoquinone-Sulfobutylether-β-Cyclodextrin Inclusion Complex for Anticancer Applications. Molecules 2023; 28:4096. [PMID: 37241838 PMCID: PMC10223034 DOI: 10.3390/molecules28104096] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 05/10/2023] [Accepted: 05/12/2023] [Indexed: 05/28/2023] Open
Abstract
Thymoquinone (TQ) is a quinone derived from the black seed Nigella sativa and has been extensively studied in pharmaceutical and nutraceutical research due to its therapeutic potential and pharmacological properties. Although the chemopreventive and potential anticancer effects of TQ have been reported, its limited solubility and poor delivery remain the major limitations. In this study, we aimed to characterize the inclusion complexes of TQ with Sulfobutylether-β-cyclodextrin (SBE-β-CD) at four different temperatures (293-318 K). Additionally, we compared the antiproliferative activity of TQ alone to TQ complexed with SBE-β-CD on six different cancer cell lines, including colon, breast, and liver cancer cells (HCT-116, HT-29, MDA-MB-231, MCF-7, SK-BR-3, and HepG2), using an MTT assay. We calculated the thermodynamic parameters (ΔH, ΔS, and ΔG) using the van't Holf equation. The inclusion complexes were characterized by X-ray diffraction (XRD), Fourier transforms infrared (FT-IR), and molecular dynamics using the PM6 model. Our findings revealed that the solubility of TQ was improved by ≥60 folds, allowing TQ to penetrate completely into the cavity of SBE-β-CD. The IC50 values of TQ/SBE-β-CD ranged from 0.1 ± 0.01 µg/mL against SK-BR-3 human breast cancer cells to 1.2 ± 0.16 µg/mL against HCT-116 human colorectal cancer cells, depending on the cell line. In comparison, the IC50 values of TQ alone ranged from 0.2 ± 0.01 µg/mL to 4.7 ± 0.21 µg/mL. Overall, our results suggest that SBE-β-CD can enhance the anticancer effect of TQ by increasing its solubility and bioavailability and cellular uptake. However, further studies are necessary to fully understand the underlying mechanisms and potential side effects of using SBE-β-CD as a drug delivery system for TQ.
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Affiliation(s)
- Eltayeb E. M. Eid
- Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unaizah 51911, Saudi Arabia
| | - Amer A. Almaiman
- Unit of Scientific Research, Applied College, Qassim University, Unaizah 51911, Saudi Arabia
| | | | - Wardah Alsalemi
- Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Sareh Kamran
- Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - FakhrEldin O. Suliman
- Department of Chemistry, College of Science, Sultan Qaboos University, P.O. Box 36, Muscat 123, Oman
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Ghelichkhani S, Saffari-Chaleshtori J, Ghaffari F, Nili-Ahmadabadi A. The Cytotoxic Effect of Thymoquinone Enhance on HepG2 Cell Line due to Induction of Fenton Reaction by Hydrogen Peroxide: An In Vitro and In Silico Study. Asian Pac J Cancer Prev 2023; 24:1809-1815. [PMID: 37247304 PMCID: PMC10495912 DOI: 10.31557/apjcp.2023.24.5.1809] [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: 02/11/2023] [Accepted: 05/20/2023] [Indexed: 05/31/2023] Open
Abstract
OBJECTIVE Thymoquinone (TQ) is a component derived from the volatile oil of Nigella sativa. Fenton reaction induction is a well-known strategy to prevent the growth of cancer cells which can stimulate by hydrogen peroxide. This study was designed to investigate the TQ effects on hydrogen peroxide-induced cytotoxicity. METHODS In this study, HepG2 cell survival, reactive oxygen species (ROS) production, cell membrane integrity, and changes of superoxide dismutase (SOD)/ catalase (CAT) activity were evaluated following incubation of HepG2 cells with 31 μM hydrogen peroxide and different concentrations of TQ (18.5, 37 and 75 μM). In addition, molecular docking studies on the interference of TQ with CAT/SOD enzymes were investigated. RESULTS Our findings showed that TQ low concentration can increase the survival of HepG2 cells when exposed to hydrogen peroxide, and on the contrary, its high concentration can potentiate cytotoxicity induced by hydrogen peroxide. The TQ alongside hydrogen peroxide increased the production of ROS, which was related to increase CAT and SOD activity in the HepG2 cells. Molecular docking findings showed that TQ effects on the formation of free radicals were not related to its chemical interference with the structure of the SOD/CAT molecules. CONCLUSION Fenton reaction induction may increase the effectiveness of TQ in preventing HepG2 cells proliferation.
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Affiliation(s)
- Sara Ghelichkhani
- 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.
| | - Javad Saffari-Chaleshtori
- Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
| | - Fatemeh Ghaffari
- 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.
| | - 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.
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Kavyani Z, Musazadeh V, Golpour-Hamedani S, Moridpour AH, Vajdi M, Askari G. The effect of Nigella sativa (black seed) on biomarkers of inflammation and oxidative stress: an updated systematic review and meta-analysis of randomized controlled trials. Inflammopharmacology 2023; 31:1149-1165. [PMID: 37036558 DOI: 10.1007/s10787-023-01213-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Accepted: 03/25/2023] [Indexed: 04/11/2023]
Abstract
OBJECTIVE This study was conducted to assess the effect of Nigella sativa (N. sativa) supplementation on inflammatory and oxidative markers among the adult population. METHODS We carried out a comprehensive, systematic search of Scopus, Embase, Cochrane Library, Web of Science, PubMed, and Google Scholar till December 2022. A random-effects model was used to estimate the overall effect size. RESULTS In total, twenty trials consisting of 1086 participants were included in the meta-analysis. Findings from 20 RCTs included in the meta-analysis suggest that N. sativa supplementation could significantly reduce serum C-reactive protein (CRP) (SMD = - 2.28; 95% CI - 3.20, - 1.37, p < 0.001), tumour necrosis factor α (TNFα) (SMD = - 1.21; 95% CI - 2.15, - 0.26; p = 0.013), and malondialdehyde (MDA) (SMD = - 2.15; 95% CI - 3.37, - 0.93, p < 0.001) levels, and significantly improves total antioxidant capacity (TAC) (SMD = 2.28; 95% CI 1.29, 3.27, p < 0.001), glutathione peroxidase (GPx) (SMD = 1.23, 95% CI 0.25, 2.22; p = 0.014) and superoxide dismutase (SOD) (SMD = 2.05; 95% CI 1.22, 2.88, p < 0.001) levels. However, no significant reduction was found in interleukin 6 (IL-6) levels (SMD = - 1.13; 95% CI - 2.72, 0.46, p = 0.162). CONCLUSION N. sativa supplementation had beneficial effects on CRP, TNF-α, MDA, SOD, GPx, and TAC. Thus, Nigella sativa can be recommended as an adjuvant anti-oxidant agent and anti-inflammatory.
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Affiliation(s)
- Zeynab Kavyani
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Vali Musazadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | | | - Mahdi Vajdi
- Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Gholamreza Askari
- Department of Community Nutrition, School of Nutrition and Food Science, Nutrition and Food Security Research Center, Isfahan University of Medical Science, Isfahan, Iran.
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Jarmakiewicz-Czaja S, Zielińska M, Helma K, Sokal A, Filip R. Effect of Nigella sativa on Selected Gastrointestinal Diseases. Curr Issues Mol Biol 2023; 45:3016-3034. [PMID: 37185722 PMCID: PMC10136991 DOI: 10.3390/cimb45040198] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/28/2023] [Accepted: 03/30/2023] [Indexed: 04/07/2023] Open
Abstract
Nigella sativa L. (family Ranunculaceae), also known as black cumin, has been used in cuisine around the world for many years. Due to its health-promoting properties, it can be used not only in the food industry but also in medicine. The main bioactive compound contained in the black cumin extract is thymoquinone (TQ), which has a special therapeutic role. The results of research in recent years confirmed its hypoglycemic, hypolipemic, and hepatoprotective effects, among others. In addition, the results of laboratory tests also indicate its immunomodulatory and anticancer effects, although there is still a lack of data on the mechanisms of how they are involved in the fight against cancer. Including this plant material in one’s diet can be both an element of prophylaxis and therapy supporting the treatment process, including pharmacological treatment. However, attention should be paid to its potential interactions with drugs used in the treatment of chronic diseases.
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Affiliation(s)
| | - Magdalena Zielińska
- Institute of Health Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
| | - Kacper Helma
- Institute of Health Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
| | - Aneta Sokal
- Institute of Health Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
| | - Rafał Filip
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
- Department of Gastroenterology with IBD Unit, Clinical Hospital No. 2, 35-301 Rzeszow, Poland
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Hidayati T, Indrayanti I, Darmawan E, Akrom A. Herbal Honey Preparations of Curcuma Xanthorriza and Black Cumin Protect against Carcinogenesis through Antioxidant and Immunomodulatory Activities in Sprague Dawley (SD) Rats Induced with Dimethylbenz(a)anthracene. Nutrients 2023; 15:nu15020371. [PMID: 36678242 PMCID: PMC9867330 DOI: 10.3390/nu15020371] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/28/2022] [Accepted: 12/30/2022] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Traditionally, Curcuma xanthorriza (CX), black cumin seed (BC), and honey have been used by the Indonesian people as medicinal ingredients to treat various health symptoms. CX extracts and BC have been proven in the laboratory as chemopreventive agents, antioxidants, and immunomodulators. In this study, we developed CX extract, BC oil, and honey into herbal honey preparations (CXBCH) and hypothesized that the preparations show chemopreventive activity. The purpose of the study was to determine the CXBCH potential as chemopreventive, antioxidant, and immunomodulatory. METHOD In this experimental laboratory research, antioxidant, immunomodulatory, and cytotoxic activities were tested on human mammary cancer cell lines (T47D cells) while the chemopreventive activity of the CXBCH preparations on Sprague Dawley (SD) rats induced with dimethylbenzene(a)anthracene (DMBA). RESULTS CXBCH preparations demonstrated immunomodulatory, antioxidant, and cytotoxic activities in T47D, Hela, and HTB-183 cells and in DMBA-induced SD rats, as the preparations inhibited tumor nodule formation, increased the number of CD4, CD8 and CD4CD25 cells, and glutathione-S-transferase (GST) activity, and decreased serum NO levels. CONCLUSIONS CXBCH preparations display chemopreventive, antioxidant, and immunomodulatory properties.
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Affiliation(s)
- Titiek Hidayati
- Department of Public Health and Family Medicine, Faculty of Medicine and Health Science, Universitas Muhammadiyah Yogyakarta, Yogyakarta 55252, Indonesia
- Correspondence: (T.H.); (A.A.)
| | - Indrayanti Indrayanti
- Department of Anatomical Pathology, Faculty of Medicine and Health Science, Universitas Muhammadiyah Yogyakarta, Yogyakarta 55252, Indonesia
| | - Endang Darmawan
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta 55252, Indonesia
| | - Akrom Akrom
- Department of Pharmacology and Clinical Pharmacy, Master Pharmacy Degree Program, Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta 55252, Indonesia
- Ahmad Dahlan Drug Information and Research Center, Universitas Ahmad Dahlan, Yogyakarta 55252, Indonesia
- Correspondence: (T.H.); (A.A.)
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Hemmati Bushehri R, Navabi P, Saeedifar AM, Keshavarzian N, Hosseini Rouzbahani N, Mosayebi G, Ghazavi A, Ghorban K, Ganji A. Integration of phytotherapy and chemotherapy: Recent advances in anticancer molecular pathways. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2023; 26:987-1000. [PMID: 37605725 PMCID: PMC10440131 DOI: 10.22038/ijbms.2023.69979.15222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 05/20/2023] [Indexed: 08/23/2023]
Abstract
Cancer is a disease characterized by abnormal and uncontrolled growth of cells, leading to invasion and metastasis to other tissues. Chemotherapy drugs are some of the primary treatments for cancer, which could detrimentally affect the cancer cells by various molecular mechanisms like apoptosis and cell cycle arrest. These treatment lines have always aligned with side effects and drug resistance. Due to their anticancer effects, medicinal herbs and their active derivative compounds are being profoundly used as complementary treatments for cancer. Many studies have shown that herbal ingredients exert antitumor activities and immune-modulation effects and have fewer side effects. On the other hand, combining phytotherapy and chemotherapy, with their synergistic effects, has gained much attention across the medical community. This review article discussed the therapeutic effects of essential herbal active ingredients combined with chemotherapeutic drugs in cancer therapy. To write this article, PubMed and Scopus database were searched with the keywords "Cancer," "Combination," "Herbal," "Traditional," and "Natural." After applying inclusion/exclusion criteria, 110 articles were considered. The study shows the anticancer effects of the active herbal ingredients by inducing apoptosis and cell cycle arrest in cancer cells, especially with a chemotherapeutic agent. This study also indicates that herbal compounds can reduce side effects and dosage, potentiate anticancer responses, and sensitize cancer cells to chemotherapy drugs.
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Affiliation(s)
| | - Parnian Navabi
- Department of Immunology, School of Medicine, Arak University of Medical Sciences, Arak, Iran
| | | | - Nafiseh Keshavarzian
- Department of Immunology, School of Medicine, Arak University of Medical Sciences, Arak, Iran
| | | | - Ghasem Mosayebi
- Department of Immunology, School of Medicine, Arak University of Medical Sciences, Arak, Iran
- Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran
| | - Ali Ghazavi
- Department of Immunology, School of Medicine, Arak University of Medical Sciences, Arak, Iran
- Traditional and Complementary Medicine Research Center (TCMRC), Arak University of Medical Sciences, Arak, Iran
| | - Khodayar Ghorban
- Department of Immunology, Medical School, Aja University of Medical Sciences, Tehran, Iran
| | - Ali Ganji
- Department of Immunology, School of Medicine, Arak University of Medical Sciences, Arak, Iran
- Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran
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Nithya G, Santhanasabapathy R, Vanitha MK, Anandakumar P, Sakthisekaran D. Antioxidant, antiproliferative, and apoptotic activity of thymoquinone against benzo(a)pyrene-induced experimental lung cancer. J Biochem Mol Toxicol 2023; 37:e23230. [PMID: 36193556 DOI: 10.1002/jbt.23230] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 08/09/2022] [Accepted: 09/16/2022] [Indexed: 01/18/2023]
Abstract
Several studies have suggested that increased consumption of phytochemicals is a comparatively easy and practical strategy to significantly decrease the incidence of cancer. In the present study, we have reported the protective effect of a natural compound, thymoquinone (TQ) against benzo(a)pyrene (B(a)P)-induced lung carcinogenesis in Swiss albino mice. B(a)P (50 mg/kg body weight) was administered twice weekly for four successive weeks and left until 20 weeks to induce lung cancer in mice. TQ (20 mg/kg body weight) was given orally as a pretreatment and posttreatment drug to determine its chemopreventive and therapeutic effects. B(a)P-induced lung cancer-bearing animals displayed cachexia-like symptoms along with an abnormal increase in lung weight and the activities of marker enzymes adenosine deaminase, aryl hydrocarbon hydroxylase, gamma-glutamyl transpeptidase, 5'-nucleotidase and lactate dehydrogenase; tumor marker carcinoembryonic antigen levels. Furthermore, B(a)P-induced animals showed elevated levels of lipid peroxides with subsequent depletion in the antioxidant status and histological aberrations. These anomalies were accompanied by increased expressions of proliferating cell nuclear antigen and cyclin D1 in the lung sections derived from B(a)P-induced animals. On TQ treatment, all the above alterations were returned to near normalcy. Furthermore, TQ administration in B(a)P-induced animals downregulated phosphatidylinositol 3-kinase/protein kinase B signaling pathway and induced apoptosis as evidenced by a decrease in cytochrome c, proapoptotic Bax, caspase-3, and p53 with a parallel increase in antiapoptotic Bcl-2. Our present results demonstrate the potential effectiveness of TQ as an antioxidant, antiproliferative, and apoptotic agent against B(a)P-induced experimental lung tumorigenesis.
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Affiliation(s)
- Gajendran Nithya
- Department of Medical Biochemistry, Dr. ALM PGIBMS, University of Madras, Taramani Campus, Chennai, Tamil Nadu, India
| | | | - Manickam Kalappan Vanitha
- Department of Medical Biochemistry, Dr. ALM PGIBMS, University of Madras, Taramani Campus, Chennai, Tamil Nadu, India
| | | | - Dhanapalan Sakthisekaran
- Department of Medical Biochemistry, Dr. ALM PGIBMS, University of Madras, Taramani Campus, Chennai, Tamil Nadu, India
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Torres-Vargas JA, Cheng-Sánchez I, Martínez-Poveda B, Medina MÁ, Sarabia F, García-Caballero M, Quesada AR. Characterization of the activity and the mechanism of action of a new toluquinol derivative with improved potential as an antiangiogenic drug. Biomed Pharmacother 2022; 155:113759. [DOI: 10.1016/j.biopha.2022.113759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 09/12/2022] [Accepted: 09/26/2022] [Indexed: 11/02/2022] Open
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Kłos P, Perużyńska M, Baśkiewicz-Hałasa M, Skupin-Mrugalska P, Majcher M, Sawczuk M, Szostak B, Droździk M, Machaliński B, Chlubek D. Response of Skin-Derived and Metastatic Human Malignant Melanoma Cell Lines to Thymoquinone and Thymoquinone-Loaded Liposomes. Pharmaceutics 2022; 14:2309. [PMID: 36365127 PMCID: PMC9698994 DOI: 10.3390/pharmaceutics14112309] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/19/2022] [Accepted: 10/25/2022] [Indexed: 09/29/2023] Open
Abstract
Thymoquinone has been proved to be effective against neoplasms, including skin cancer. Its high lipophilicity, however, may limit its potential use as a drug. Melanoma remains the deadliest of all skin cancers worldwide, due to its high heterogeneity, depending on the stage of the disease. Our goal was to compare the anti-cancer activity of free thymoquinone and thymoquinone-loaded liposomes on two melanoma cell lines that originated from different stages of this cancer: skin-derived A375 and metastatic WM9. We evaluated the proapoptotic effects of free thymoquinone by flow cytometry and Western blot, and its mitotoxicity by means of JC-1 assay. Additionally, we compared the cytotoxicity of free thymoquinone and thymoquinone in liposomes by WST-1 assay. Our results revealed a higher antiproliferative effect of TQ in WM9 cells, whereas its higher proapoptotic activity was observed in the A375 cell line. Moreover, the thymoquinone-loaded liposome was proved to exert stronger cytotoxic effect on both cell lines studied than free thymoquinone. Differences in the response of melanoma cells derived from different stages of the disease to thymoquinone, as well as their different responses to free and carrier-delivered thymoquinone, are essential for the development of new anti-melanoma therapies. However, further research is required to fully understand them.
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Affiliation(s)
- Patrycja Kłos
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| | - Magdalena Perużyńska
- Department of Experimental and Clinical Pharmacology, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| | - Magdalena Baśkiewicz-Hałasa
- Department of General Pathology, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| | - Paulina Skupin-Mrugalska
- Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
| | - Małgorzata Majcher
- Faculty of Food Science and Nutrition, Poznań University of Life Sciences, Wojska Polskiego 31, 60-624 Poznan, Poland
| | - Magdalena Sawczuk
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| | - Bartosz Szostak
- Department of Physiology, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| | - Marek Droździk
- Department of Experimental and Clinical Pharmacology, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| | - Bogusław Machaliński
- Department of General Pathology, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| | - Dariusz Chlubek
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
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Banik A, Ahmed SR, Sajib EH, Deb A, Sinha S, Azim KF. Identification of potential inhibitory analogs of metastasis tumor antigens (MTAs) using bioactive compounds: revealing therapeutic option to prevent malignancy. Mol Divers 2022; 26:2473-2502. [PMID: 34743299 DOI: 10.1007/s11030-021-10345-w] [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: 02/19/2021] [Accepted: 10/24/2021] [Indexed: 12/31/2022]
Abstract
The deeper understanding of metastasis phenomenon and detection of drug targets could be a potential approach to minimize cancer mortality. In this study, attempts were taken to unmask novel therapeutics to prevent metastasis and cancer progression. Initially, we explored the physiochemical, structural and functional insights of three metastasis tumor antigens (MTAs) and evaluated some plant-based bioactive compounds as potent MTA inhibitors. From 50 plant metabolites screened, isoflavone, gingerol, citronellal and asiatic acid showed maximum binding affinity with all three MTA proteins. The ADME analysis detected no undesirable toxicity that could reduce the drug likeness properties of top plant metabolites. Moreover, molecular dynamics studies revealed that the complexes were stable and showed minimum fluctuation at molecular level. We further performed ligand-based virtual screening to identify similar drug molecules using a large collection of 376,342 compounds from DrugBank. The results suggested that several structural analogs (e.g., tramadol, nabumetone, DGLA and hydrocortisone) may act as agonist to block the MTA proteins and inhibit cancer progression at early stage. The study could be useful to develop effective medications against cancer metastasis in future. Due to encouraging results, we highly recommend further in vitro and in vivo trials for the experimental validation of the findings.
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Affiliation(s)
- Anik Banik
- Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, Bangladesh
- Department of Plant and Environmental Biotechnology, Sylhet Agricultural University, Sylhet, 3100, Bangladesh
| | - Sheikh Rashel Ahmed
- Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, Bangladesh
- Department of Plant and Environmental Biotechnology, Sylhet Agricultural University, Sylhet, 3100, Bangladesh
| | - Emran Hossain Sajib
- Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, Bangladesh
| | - Anamika Deb
- Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, Bangladesh
| | - Shiuly Sinha
- Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet, 3100, Bangladesh
| | - Kazi Faizul Azim
- Department of Microbial Biotechnology, Sylhet Agricultural University, Sylhet, 3100, Bangladesh.
- Faculté de Pharmacie, Université de Tours, 37200, Tours, France.
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Chemopreventive Efficacy of Thymoquinone in Chemically Induced Urinary Bladder Carcinogenesis in Rat. BIOMED RESEARCH INTERNATIONAL 2022; 2022:6276768. [PMID: 36158887 PMCID: PMC9499785 DOI: 10.1155/2022/6276768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 08/30/2022] [Indexed: 11/18/2022]
Abstract
The effects of thymoquinone (TQ) in a carcinogen-based models of urinary bladder cancer were evaluated, using 45 male rats in five groups. In negative control (
), only tap water was given. In positive control (
), the rats received 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in drinking water for 9 weeks. In preventive groups with 25 mg/kg (
) and 50 mg/kg (
), oral TQ was concurrently given with 0.05% BBN for 9 weeks and continued for one more week after cessation of BBN. Preventive-treatment group (
) received 50 mg/kg TQ orally for 20 weeks. Five rats from each group were sequentially sacrificed in two phases: the induction phase at 12th week (except the last group) and the rest in postinduction phase at 20th week. The bladders were examined macroscopically for lesion formation, and the masses were submitted for histopathological evaluation. Markers for total oxidant status (TOS), inflammation (nuclear factor kappa B (NF-κB)), and angiogenesis (vascular endothelial growth factor (VEGF)) were also assessed. There was a reduced number of bladder lesions in the TQ groups versus the carcinogen group at both phases. Histopathological findings demonstrated a significant improvement in the abnormal morphological changes in the urothelium of the TQ-treated groups. Thymoquinone exerted a significant antioxidant and anti-inflammatory effect by a decrease in serum level of TOS and NF-κB at week 12 which was maintained low in phase two at week 20. The serum level of VEGF was also alleviated in the induction phase at week 12 and maintained low in postinduction period. In TQ preventive-treatment approach, a nonsignificant elevation of serum level of TOS and NF-κB and slight reduction in VEGF were observed at the end of the experiment. These data suggest that TQ may be effective in preventing bladder carcinogenesis, and the suggested mechanisms might be related to antioxidant, prooxidant, and anti-inflammatory properties of TQ.
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Atanase LI, Salhi S, Cucoveica O, Ponjavic M, Nikodinovic-Runic J, Delaite C. Biodegradability Assessment of Polyester Copolymers Based on Poly(ethylene adipate) and Poly(ε-caprolactone). Polymers (Basel) 2022; 14:polym14183736. [PMID: 36145879 PMCID: PMC9504934 DOI: 10.3390/polym14183736] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 08/30/2022] [Accepted: 09/02/2022] [Indexed: 12/19/2022] Open
Abstract
Biodegradable polymers contain chains that are hydrolytically or enzymatically cleaved, resulting in soluble degradation products. Biodegradability is particularly desired in biomedical applications, in which degradation of the polymer ensures clearance from the body and eliminates the need for retrieval or explant. In this study, a homologues series of poly(ε-caprolactone)-b-poly(ethylene adipate)-b-poly(ε-caprolactone) (PCL-b-PEA-b-PCL) block copolymers, with constant PEA molar mass and different PCL sequence lengths was obtained. The starting point of these copolymers was a dihydroxy-PEA precursor with a molar mass (Mn) of 2500 g/mol. Mn values of the PCL varied between 1000 and 10,000 g/mol. Both the precursors and the copolymers were characterized using different physicochemical methods, such as: NMR, SEC, Maldi-TOFF, DSC, and ATG. The molecular characteristics of the copolymers were in a direct correlation with the sequence length of the PCL. Enzymatic degradability studies were also conducted by using cell-free extract containing Pseudomonas aeruginosa PAO1 for 10 and 21 days, and it appeared that the presence of the PEA central sequence has an important influence on the biodegradability of the copolymer samples. In fact, copolymer PCL7000-PEA2500-PCL7000 had a weight loss of around 50% after 10 days whereas the weight loss of the homopolymer PCL, with a similar Mn of 14,000 g/mol, was only 6%. The results obtained in this study indicate that these copolymer samples can be further used for the preparation of drug delivery systems with modulated biodegradability.
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Affiliation(s)
- Leonard Ionut Atanase
- Faculty of Medical Dentistry, Apollonia University of Iasi, 700511 Iasi, Romania
- Academy of Romanian Scientists, 050045 Bucharest, Romania
- Correspondence:
| | - Slim Salhi
- Laboratoire de Chimie Appliquée, Faculté des Sciences de Sfax, University of Sfax, Sfax 3029, Tunisia
| | - Oana Cucoveica
- Faculty of Medical Dentistry, Apollonia University of Iasi, 700511 Iasi, Romania
- “Cristofor Simionescu” Faculty of Chemical Engineering and Environmental Protection, “Gheorghe Asachi” Technical University of Iasi, 700050 Iasi, Romania
| | - Marijana Ponjavic
- Department of Electrochemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, 11000 Belgrade, Serbia
| | - Jasmina Nikodinovic-Runic
- Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000 Belgrade, Serbia
| | - Christelle Delaite
- Laboratoire de Photochimie et d’Ingenierie Macromoleculaires (LPIM), University of Haute Alsace, 68100 Mulhouse, France
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Zineh BR, Roshangar L, Meshgi S, Shabgard M. 3D printing of alginate/thymoquinone/halloysite nanotube bio-scaffolds for cartilage repairs: experimental and numerical study. Med Biol Eng Comput 2022; 60:3069-3080. [DOI: 10.1007/s11517-022-02654-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 03/25/2022] [Indexed: 11/29/2022]
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Khatib S, Sobeh M, Bouissane L. Tetraclinis articulata (vahl) masters: An insight into its ethnobotany, phytochemistry, toxicity, biocide and therapeutic merits. Front Pharmacol 2022; 13:977726. [PMID: 36133819 PMCID: PMC9483659 DOI: 10.3389/fphar.2022.977726] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
Tetraclinis articulata (Vahl) Masters, commonly known as Sandarac tree and Araâr, is the only species representing the genus Tetraclinis Masters. The plant has been extensively used for medicinal, artistic, and ritual purposes since its first recorded use in 1800 B.C. Recently, a full range of ethnobotanical investigations has been undertaken to document the plant’s empirical knowledge. They reported the use of different parts, such as leaves, stems, cones, bark, and roots, as part of folk healing practices to manage diabetes mellitus, hypertension, fever, stomach disorders, and diarrhea, among others. The phytochemical studies have identified at least 130 compounds from leaves, cones, resin, bark, and woods. These chemical constituents are categorized into phenolic acids, flavonoids and their derivatives, volatile compounds, phytosterols, and fatty acids, among others. Furthermore, they have strongly been correlated with the promising antimicrobial, antioxidant, neuroprotective, antiurolithiatic, anti-inflammatory, antidiabetic, and cytotoxic properties of the plant. Toxicological studies argued that the plant is quite safe and devoid of eventual toxicity; however, in-depth investigations are required to validate the safety of the plant. The remarkable antimicrobial and antioxidant potencies of various extracts from the plant against a wide range of foodborne pathogens support their possible use to increase the shelf life of foodstuffs in the food industry. Likewise, various plant-based extracts have been proven to exert substantial biocidal properties, making them potential alternatives to synthetic pesticides in agriculture. The present review provides an up-to-date comprehensive insight about the ethnobotanical uses of T. articulata, along with its phytochemistry and biological activities to furnish directions for further studies. We also discussed the biocidal potency of the plant and highlighted its usage to extend the shelf life of perishable foods.
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Affiliation(s)
- Sohaib Khatib
- Molecular Chemistry, Materials and Catalysis Laboratory, Faculty of Sciences and Technologies, Sultan Moulay Slimane University, Beni-Mellal, Morocco
| | - Mansour Sobeh
- Agro Bio Sciences, Mohammed VI Polytechnic University, Ben‐Guerir, Morocco
- *Correspondence: Mansour Sobeh, ; Latifa Bouissane,
| | - Latifa Bouissane
- Molecular Chemistry, Materials and Catalysis Laboratory, Faculty of Sciences and Technologies, Sultan Moulay Slimane University, Beni-Mellal, Morocco
- *Correspondence: Mansour Sobeh, ; Latifa Bouissane,
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Al Zarzour RH, Kamarulzaman EE, Saqallah FG, Zakaria F, Asif M, Abdul Razak KN. Medicinal plants' proposed nanocomposites for the management of endocrine disorders. Heliyon 2022; 8:e10665. [PMID: 36185142 PMCID: PMC9520215 DOI: 10.1016/j.heliyon.2022.e10665] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 05/07/2022] [Accepted: 09/09/2022] [Indexed: 01/14/2023] Open
Abstract
Extensive attention has been focused on herbal medicine for the treatment of different endocrine disorders. In fact, compelling scientific evidence indicates that natural compounds might act as endocrine modulators by mimicking, stimulating, or inhibiting the actions of different hormones, such as thyroid, sex, steroidal, and glucose regulating hormones. These potentials might be effectively employed for therapeutic purposes related to the endocrine system as novel complementary choices. Nevertheless, despite the remarkable therapeutic effects, inadequate targeting efficiency and low aqueous solubility of the bioactive components are still essential challenges in their clinical accreditation. On the other hand, nanotechnology has pushed the wheels of combining inorganic nanoparticles with biological structures of medicinal bioactive compounds as one of the utmost exciting fields of research. Nanoparticle conjugations create an inclusive array of applications that provide greater compliance, higher bioavailability, and lower dosage. This can safeguard the global availability of these wealthy natural sources, regardless of their biological occurrence. This review inspects future challenges of medicinal plants in various endocrine disorders for safe and alternative treatments with examples of their nanoparticle formulations.
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Affiliation(s)
- Raghdaa Hamdan Al Zarzour
- Discipline of Physiology & Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia
- Department of Pharmacology, Faculty of Pharmacy, Arab International University, Daraa Highway, Ghabagheb Syria
| | - Ezatul Ezleen Kamarulzaman
- Discipline of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia
| | - Fadi G. Saqallah
- Discipline of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia
| | - Fauziahanim Zakaria
- Discipline of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia
| | - Muhammad Asif
- Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, 63100 Punjab, Pakistan
| | - Khairul Niza Abdul Razak
- Discipline of Physiology & Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia
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Alam M, Hasan GM, Ansari MM, Sharma R, Yadav DK, Hassan MI. Therapeutic implications and clinical manifestations of thymoquinone. PHYTOCHEMISTRY 2022; 200:113213. [PMID: 35472482 DOI: 10.1016/j.phytochem.2022.113213] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 04/16/2022] [Accepted: 04/17/2022] [Indexed: 06/14/2023]
Abstract
Thymoquinone (TQ), a natural phytochemical predominantly found in Nigella sativa, has been investigated for its numerous health benefits. TQ showed anti-cancer, anti-oxidant, and anti-inflammatory properties, validated in various disease models. The anti-cancer potential of TQ is goverened by anti-proliferation, cell cycle arrest, apoptosis induction, ROS production, anti-metastasis and anti-angiogenesis, inhibition of cell migration and invasion action. Additionally, TQ exhibited antitumor activity via the modulation of multiple pathways and molecular targets, including Akt, ERK1/2, STAT3, and NF-κB. The present review highlighted the anticancer potential of TQ . We summarize the anti-cancer, anti-oxidant, and anti-inflammatory properties of TQ, focusing on its molecular targets and its promising action in cancer therapy. We further described the molecular mechanisms by which TQ prevents signaling pathways that mediate cancer progression, invasion, and metastasis.
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Affiliation(s)
- Manzar Alam
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Gulam Mustafa Hasan
- Department of Biochemistry, College of Medicine, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj, 11942, Saudi Arabia
| | - Md Meraj Ansari
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Mohali, Punjab, 160062, India
| | - Rishi Sharma
- Department of Forensic Medicine and Toxicology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, 249203, India
| | - Dharmendra Kumar Yadav
- College of Pharmacy, Gachon University of Medicine and Science, Hambakmoeiro, Yeonsu-gu, Incheon City, 21924, South Korea.
| | - Md Imtaiyaz Hassan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
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41
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Talib WH, Daoud S, Mahmod AI, Hamed RA, Awajan D, Abuarab SF, Odeh LH, Khater S, Al Kury LT. Plants as a Source of Anticancer Agents: From Bench to Bedside. Molecules 2022; 27:molecules27154818. [PMID: 35956766 PMCID: PMC9369847 DOI: 10.3390/molecules27154818] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/18/2022] [Accepted: 07/21/2022] [Indexed: 12/03/2022] Open
Abstract
Cancer is the second leading cause of death after cardiovascular diseases. Conventional anticancer therapies are associated with lack of selectivity and serious side effects. Cancer hallmarks are biological capabilities acquired by cancer cells during neoplastic transformation. Targeting multiple cancer hallmarks is a promising strategy to treat cancer. The diversity in chemical structure and the relatively low toxicity make plant-derived natural products a promising source for the development of new and more effective anticancer therapies that have the capacity to target multiple hallmarks in cancer. In this review, we discussed the anticancer activities of ten natural products extracted from plants. The majority of these products inhibit cancer by targeting multiple cancer hallmarks, and many of these chemicals have reached clinical applications. Studies discussed in this review provide a solid ground for researchers and physicians to design more effective combination anticancer therapies using plant-derived natural products.
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Affiliation(s)
- Wamidh H. Talib
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman 11931, Jordan; (A.I.M.); (R.A.H.); (D.A.); (S.F.A.); (L.H.O.); (S.K.)
- Correspondence:
| | - Safa Daoud
- Department Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmacy, Applied Science Private University, Amman 11931, Jordan;
| | - Asma Ismail Mahmod
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman 11931, Jordan; (A.I.M.); (R.A.H.); (D.A.); (S.F.A.); (L.H.O.); (S.K.)
| | - Reem Ali Hamed
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman 11931, Jordan; (A.I.M.); (R.A.H.); (D.A.); (S.F.A.); (L.H.O.); (S.K.)
| | - Dima Awajan
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman 11931, Jordan; (A.I.M.); (R.A.H.); (D.A.); (S.F.A.); (L.H.O.); (S.K.)
| | - Sara Feras Abuarab
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman 11931, Jordan; (A.I.M.); (R.A.H.); (D.A.); (S.F.A.); (L.H.O.); (S.K.)
| | - Lena Hisham Odeh
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman 11931, Jordan; (A.I.M.); (R.A.H.); (D.A.); (S.F.A.); (L.H.O.); (S.K.)
| | - Samar Khater
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman 11931, Jordan; (A.I.M.); (R.A.H.); (D.A.); (S.F.A.); (L.H.O.); (S.K.)
| | - Lina T. Al Kury
- Department of Health Sciences, College of Natural and Health Sciences, Zayed University, Abu Dhabi 144534, United Arab Emirates;
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Khan FZ, Mostaid MS, Apu MNH. Molecular Signaling Pathway Targeted Therapeutic Potential of Thymoquinone in Alzheimer’s disease. Heliyon 2022; 8:e09874. [PMID: 35832342 PMCID: PMC9272348 DOI: 10.1016/j.heliyon.2022.e09874] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Revised: 04/07/2022] [Accepted: 06/30/2022] [Indexed: 11/29/2022] Open
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease with rapid progression. Black cumin (Nigella sativa) is a nutraceutical that has been investigated as a prophylactic and therapeutic agent for this disease due to its ability to prevent or retard the progression of neurodegeneration. Thymoquinone (TQ) is the main bioactive compound isolated from the seeds of black cumin. Several reports have shown that it has promising potential in the prevention and treatment of AD due to its significant antioxidative, anti-inflammatory, and antiapoptotic properties along with several other mechanisms that target the altered signaling pathways due to the disease pathogenesis. In addition, it shows anticholinesterase activity and prevents α-synuclein induced synaptic damage. The aim of this review is to summarize the potential aspects and mechanisms by which TQ imparts its action in AD.
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Tabassum S, Thakur V, Rosli N, Ichwan SJA, Mishra P, Suriyah WH. Therapeutic implications of thymoquinone and its molecular and functional mechanisms against oral and lung cancer. GENE REPORTS 2022. [DOI: 10.1016/j.genrep.2022.101600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Alam P, Shakeel F, Taleuzzaman M, Foudah AI, Alqarni MH, Aljarba TM, Alshehri S, Ghoneim MM. Box-Behnken Design (BBD) Application for Optimization of Chromatographic Conditions in RP-HPLC Method Development for the Estimation of Thymoquinone in Nigella sativa Seed Powder. Processes (Basel) 2022; 10:1082. [DOI: 10.3390/pr10061082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/10/2022] Open
Abstract
Thymoquinone (THY) is a bioactive compound present in the seed powder of Nigella sativa (NS). This research aims to precisely and accurately estimate THY using high-performance liquid chromatography (HPLC) with a Quality by Design (QbD) application. Box-Behnken design (BBD) was employed to optimize the chromatographic conditions for HPLC method development, taking mobile phase flow rate, pH of the buffer, and λmax as independent variables and retention time and tailing factor as the measured responses. The mobile phase composition was methanol: acetonitrile: buffer (2.2 mM ammonium formate) at the ratio of 35:50:15 v/v/v on a Symmetry® C18 (5 μm, 3.9 × 150 mm) column. In isocratic mode, it had a flow rate 0.9 mL min−1 and eluted analyte was detected at 249 nm. Validation parameters followed the International Council for Harmonization (ICH) guidelines for the new HPLC method. The method was linear over the range 6.25–100 µg mL−1 with a coefficient of determination (r2) of 0.9957. The limit of detection (LOD) and limit of quantification (LOQ) were 2.05 and 6.25 µg mL−1, respectively. The %RSD of system suitability for retention time was 1.42% and for the tailing factor it was 0.695%. In addition, the developed method was precise, accurate, and robust according to ICH criteria. The developed HPLC method is simple, accurate, quick, and robust, and it could be used for the routine analysis of THY in different kinds of formulations.
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Affiliation(s)
- Prawez Alam
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Faiyaz Shakeel
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Mohamad Taleuzzaman
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Maulana Azad University, Village Bujhawar, Tehsil Luni, Jodhpur 342802, Rajasthan, India
| | - Ahmed I. Foudah
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Mohammed H. Alqarni
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Tariq M. Aljarba
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Sultan Alshehri
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Mohammed M. Ghoneim
- Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia
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Suvarna V, Bore B, Bhawar C, Mallya R. Complexation of phytochemicals with cyclodextrins and their derivatives- an update. Biomed Pharmacother 2022; 149:112862. [PMID: 35339826 DOI: 10.1016/j.biopha.2022.112862] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 03/13/2022] [Accepted: 03/22/2022] [Indexed: 11/02/2022] Open
Abstract
Bioactive phytochemicals from natural source have gained tremendous interest over several decades due to their wide and diverse therapeutic activities playing key role as functional food supplements, pharmaceutical and nutraceutical products. Nevertheless, their application as therapeutically active moieties and formulation into novel drug delivery systems are hindered due to major drawbacks such as poor solubility, bioavailability and dissolution rate and instability contributing to reduction in bioactivity. These drawbacks can be effectively overcome by their complexation with different cyclodextrins. Present article discusses complexation of phytochemicals varying from flavonoids, phenolics, triterpenes, and tropolone with different natural and synthetic cyclodextrins. Moreover, the article summarizes complexation methods, complexation efficiency, stability, stability constants and enhancement in rate and extent of dissolution, bioavailability, solubility, in vivo and in vitro activities of reported complexed phytochemicals. Additionally, the article presents update of published patent details comprising of complexed phytochemicals of therapeutic significance. Thus, phytochemical cyclodextrin complexes have tremendous potential for transformation into drug delivery systems as substantiated by significant outcome of research findings.
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Affiliation(s)
- Vasanti Suvarna
- Department of Pharmaceutical Chemistry and Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V.L. Mehta Road, Vile Parle (West), Mumbai 400056, Maharashtra, India.
| | - Bhunesh Bore
- Department of Pharmaceutical Chemistry and Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V.L. Mehta Road, Vile Parle (West), Mumbai 400056, Maharashtra, India
| | - Chaitanya Bhawar
- Department of Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V.L. Mehta Road, Vile Parle (West), Mumbai 400056, Maharashtra, India
| | - Rashmi Mallya
- Department of Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V.L. Mehta Road, Vile Parle (West), Mumbai 400056, Maharashtra, India
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Tewari D, Priya A, Bishayee A, Bishayee A. Targeting transforming growth factor-β signalling for cancer prevention and intervention: Recent advances in developing small molecules of natural origin. Clin Transl Med 2022; 12:e795. [PMID: 35384373 PMCID: PMC8982327 DOI: 10.1002/ctm2.795] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 03/12/2022] [Accepted: 03/16/2022] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Cancer is the world's second leading cause of death, but a significant advancement in cancer treatment has been achieved within the last few decades. However, major adverse effects and drug resistance associated with standard chemotherapy have led towards targeted treatment options. OBJECTIVES Transforming growth factor-β (TGF-β) signaling plays a key role in cell proliferation, differentiation, morphogenesis, regeneration, and tissue homeostasis. The prime objective of this review is to decipher the role of TGF-β in oncogenesis and to evaluate the potential of various natural and synthetic agents to target this dysregulated pathway to confer cancer preventive and anticancer therapeutic effects. METHODS Various authentic and scholarly databases were explored to search and obtain primary literature for this study. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria was followed for the review. RESULTS Here we provide a comprehensive and critical review of recent advances on our understanding of the effect of various bioactive natural molecules on the TGF-β signaling pathway to evaluate their full potential for cancer prevention and therapy. CONCLUSION Based on emerging evidence as presented in this work, TGF-β-targeting bioactive compounds from natural sources can serve as potential therapeutic agents for prevention and treatment of various human malignancies.
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Affiliation(s)
- Devesh Tewari
- Department of PharmacognosySchool of Pharmaceutical SciencesLovely Professional UniversityPhagwaraPunjabIndia
| | - Anu Priya
- Department of PharmacologySchool of Pharmaceutical SciencesLovely Professional UniversityPhagwaraPunjabIndia
| | | | - Anupam Bishayee
- College of Osteopathic MedicineLake Erie College of Osteopathic MedicineBradentonFloridaUSA
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Idris S, Refaat B, Almaimani RA, Ahmed HG, Ahmad J, Alhadrami M, El-Readi MZ, Elzubier ME, Alaufi HAA, Al-Amin B, Alghamdi AA, Bahwerth F, Minshawi F, Kabrah SM, Aslam A. Enhanced in vitro tumoricidal effects of 5-Fluorouracil, thymoquinone, and active vitamin D 3 triple therapy against colon cancer cells by attenuating the PI3K/AKT/mTOR pathway. Life Sci 2022; 296:120442. [PMID: 35245520 DOI: 10.1016/j.lfs.2022.120442] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 02/16/2022] [Accepted: 02/25/2022] [Indexed: 12/26/2022]
Abstract
AIMS This study measured the effects of 5-Fluorouracil (5-FU), calcitriol (VD3), and/or thymoquinone (TQ) single/dual/triple therapies on cell cycle progression, apoptosis, inhibition of the PI3K/AKT/mTOR pathway, and oxidative stress against colorectal cancer (CRC). MAIN METHODS The HT29, SW480 and SW620 cell lines were treated with 5-FU (50 μM), VD3 (25 μM), and TQ (75 μM), alone or combined for 12 h, prior to cell cycle/apoptosis analyses. KEY FINDINGS TQ monotherapy had greater anticancer effects to active VD3 or 5-FU, revealing higher expression of p21/p27/PTEN/BAX/Cyto-C/Casp-3 and increased levels of total glutathione, with inhibitions in CCND1/CCND3/BCL-2 and PI3K/AKT/mTOR molecules, alongside higher rates of apoptosis in HT29, SW480 and SW620 cells (P < 0.005 for all markers). Additionally, all combination protocols revealed enhanced modulations of the PI3K/PTEN/Akt/mTOR pathway, higher expression of p21/p27/PTEN/BAX/Cyto-C/Casp-3, and better anti-oxidant effects, than the monotherapies. Although TQ/5-FU and TQ/VD3 co-therapies were better relative to the VD3/5-FU regimen, the best tumoricidal effects were observed with triple therapy in the HT29 and SW480 cell lines, possibly by boosted attenuations of the PI3K/AKT/mTOR oncogenic pathway. In contrast, TQ single treatment was more effective than the triple therapy regimen in metastatic SW620 cells, suggesting that this protocol would be more useful therapeutically in late-stage CRC. SIGNIFICANCE In conclusion, this study is the first to demonstrated enhanced anti-tumorigenic effects for VD3, TQ, and 5-FU triple therapy against CRC cells and could represent the best strategy for treating early stages of malignancy, whereas TQ monotherapy could be a better approach for treating metastatic forms of the disease.
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Affiliation(s)
- Shakir Idris
- Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan; Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, PO Box 7607, Makkah, Saudi Arabia
| | - Bassem Refaat
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, PO Box 7607, Makkah, Saudi Arabia
| | - Riyad A Almaimani
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah, Saudi Arabia
| | - Hussain G Ahmed
- Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan
| | - Jawwad Ahmad
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, PO Box 7607, Makkah, Saudi Arabia
| | - Mai Alhadrami
- Department of Pathology, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah, Saudi Arabia
| | - Mahmoud Zaki El-Readi
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah, Saudi Arabia; Biochemistry Department, Faculty of Pharmacy, Al-Azhar University, Assuit, Egypt
| | - Mohamed E Elzubier
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah, Saudi Arabia
| | - Haneen A A Alaufi
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, PO Box 7607, Makkah, Saudi Arabia; Pathology and Laboratory Medicine, Department of Anatomic Medicine, Prince Mohammed Bin Abdul Aziz Hospital, Madinah, Saudi Arabia
| | - Badriah Al-Amin
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, PO Box 7607, Makkah, Saudi Arabia
| | - Ahmad A Alghamdi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia
| | - Fayez Bahwerth
- Laboratory and Blood Bank Department, King Faisal Hospital, Makkah, Saudi Arabia
| | - Faisal Minshawi
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, PO Box 7607, Makkah, Saudi Arabia
| | - Saeed M Kabrah
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, PO Box 7607, Makkah, Saudi Arabia
| | - Akhmed Aslam
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, PO Box 7607, Makkah, Saudi Arabia.
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Ali S, Alam M, Khatoon F, Fatima U, Elasbali AM, Adnan M, Islam A, Hassan MI, Snoussi M, De Feo V. Natural products can be used in therapeutic management of COVID-19: Probable mechanistic insights. Biomed Pharmacother 2022; 147:112658. [PMID: 35066300 PMCID: PMC8769927 DOI: 10.1016/j.biopha.2022.112658] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 01/18/2022] [Accepted: 01/18/2022] [Indexed: 02/06/2023] Open
Abstract
The unexpected emergence of the new Coronavirus disease (COVID-19) has affected more than three hundred million individuals and resulted in more than five million deaths worldwide. The ongoing pandemic has underscored the urgent need for effective preventive and therapeutic measures to develop anti-viral therapy. The natural compounds possess various pharmaceutical properties and are reported as effective anti-virals. The interest to develop an anti-viral drug against the novel severe acute respiratory syndrome Coronavirus (SARS-CoV-2) from natural compounds has increased globally. Here, we investigated the anti-viral potential of selected promising natural products. Sources of data for this paper are current literature published in the context of therapeutic uses of phytoconstituents and their mechanism of action published in various reputed peer-reviewed journals. An extensive literature survey was done and data were critically analyzed to get deeper insights into the mechanism of action of a few important phytoconstituents. The consumption of natural products such as thymoquinone, quercetin, caffeic acid, ursolic acid, ellagic acid, vanillin, thymol, and rosmarinic acid could improve our immune response and thus possesses excellent therapeutic potential. This review focuses on the anti-viral functions of various phytoconstituent and alkaloids and their potential therapeutic implications against SARS-CoV-2. Our comprehensive analysis provides mechanistic insights into phytoconstituents to restrain viral infection and provide a better solution through natural, therapeutically active agents.
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Affiliation(s)
- Sabeeha Ali
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Manzar Alam
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Fatima Khatoon
- Amity Institute of Neuropsychology & Neurosciences, Amity University, Noida, Uttar Pradesh 201303, India
| | - Urooj Fatima
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | | | - Mohd Adnan
- Department of Biology, College of Science, University of Hail, P.O. Box 2440, Hail, Saudi Arabia
| | - Asimul Islam
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Md Imtaiyaz Hassan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Mejdi Snoussi
- Department of Biology, College of Science, University of Hail, P.O. Box 2440, Hail, Saudi Arabia
| | - Vincenzo De Feo
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, Fisciano, Italy.
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Triantafillidis JK, Triantafyllidi E, Sideris M, Pittaras T, Papalois AE. Herbals and Plants in the Treatment of Pancreatic Cancer: A Systematic Review of Experimental and Clinical Studies. Nutrients 2022; 14:619. [PMID: 35276978 PMCID: PMC8839014 DOI: 10.3390/nu14030619] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/27/2022] [Accepted: 01/27/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Pancreatic cancer represents the most lethal malignancy among all digestive cancers. Despite the therapeutic advances achieved during recent years, the prognosis of this neoplasm remains disappointing. An enormous amount of experimental (mainly) and clinical research has recently emerged referring to the effectiveness of various plants administered either alone or in combination with chemotherapeutic agents. Apart from Asian countries, the use of these plants and herbals in the treatment of digestive cancer is also increasing in a number of Western countries as well. The aim of this study is to review the available literature regarding the efficacy of plants and herbals in pancreatic cancer. METHODS The authors have reviewed all the experimental and clinical studies published in Medline and Embase, up to June 2021. RESULTS More than 100 plants and herbals were thoroughly investigated. Favorable effects concerning the inhibition of cancer cell lines in the experimental studies and a favorable clinical outcome after combining various plants with established chemotherapeutic agents were observed. These herbals and plants exerted their activity against pancreatic cancer via a number of mechanisms. The number and severity of side-effects are generally of a mild degree. CONCLUSION A quite high number of clinical and experimental studies confirmed the beneficial effect of many plants and herbals in pancreatic cancer. More large, double-blind clinical studies assessing these natural products, either alone or in combination with chemotherapeutic agents should be conducted.
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Affiliation(s)
- John K. Triantafillidis
- GI Department, Metropolitan General Hospital, 15562 Holargos, Greece;
- Hellenic Society of Gastrointestinal Oncology, 354, Iera Odos Street, Haidari, 12461 Athens, Greece;
| | - Eleni Triantafyllidi
- Hellenic Society of Gastrointestinal Oncology, 354, Iera Odos Street, Haidari, 12461 Athens, Greece;
| | - Michail Sideris
- Women’s Health Research Unit, Queen Mary University of London, London E1 2AB, UK;
| | - Theodoros Pittaras
- Hematology Laboratory-Blood Bank, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece;
| | - Apostolos E. Papalois
- Hellenic Society of Gastrointestinal Oncology, 354, Iera Odos Street, Haidari, 12461 Athens, Greece;
- Special Unit for Biomedical Research and Education, School of Medicine, Aristotle University of Thessaloniki, 60 El. Venizelou Street, Aghia Paraskevi, 15341 Athens, Greece
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Plant-Derived Terpenoids: A Promising Tool in the Fight against Melanoma. Cancers (Basel) 2022; 14:cancers14030502. [PMID: 35158770 PMCID: PMC8833325 DOI: 10.3390/cancers14030502] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 01/10/2022] [Accepted: 01/18/2022] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Despite the numerous therapies, melanoma remains the deadliest of all skin cancers; however, plant-derived terpenoids are defense molecules that have proven anti-cancer properties. In this review, we present the results of the search for anti-melanoma plant terpenoids. Additionally, we show the effects of combining terpenoids with standard drugs, radiation therapy, or other plant substances on melanoma cell lines and animal models. Finally, we present some examples of drug delivery systems that increase the uptake of terpenoids by melanoma tissue. Abstract Melanoma is responsible for the highest number of skin cancer-caused deaths worldwide. Despite the numerous melanoma-treating options, the fight against it remains challenging, mainly due to its great heterogeneity and plasticity, as well as the high toxicity of standard drugs. Plant-derived terpenoids are a group of plant defense molecules that have been proven effective in killing many different types of cancer cells, both in in vitro experiments and in vivo models. In this review, we focus on recent results in the search for plant terpenoids with anti-melanoma activity. We also report on the synergistic action of combining terpenoids with other plant-derived substances, MAP kinase inhibitors, or radiation. Additionally, we present examples of terpenoid-loaded nanoparticle carriers as anti-melanoma agents that have increased permeation through the cancer tissue.
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