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Moar K, Yadav S, Pant A, Deepika, Maurya PK. Anti-tumor Effects of Polyphenols via Targeting Cancer Driving Signaling Pathways: A Review. Indian J Clin Biochem 2024; 39:470-488. [PMID: 39346722 PMCID: PMC11436542 DOI: 10.1007/s12291-024-01222-y] [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: 02/09/2024] [Accepted: 04/02/2024] [Indexed: 10/01/2024]
Abstract
The use of drugs in chemotherapy poses numerous side effects. Hence the use of natural substances that can help in the prevention and cure of the disease is a dire necessity. Cancer is a deadly illness and combination of diseases, the menace of which is rising with every passing year. The research community and scientists from all over the world are working towards finding a cure of the disease. The use of polyphenols which are naturally derived from plants have a great potential to be used as anti-cancer drugs and also the use of fruits and vegetables which are rich in these polyphenols can also help in the prevention of diseases. The study aims to compile the available literature and research studies on the anti-cancer effects of polyphenols and the signaling pathways that are affected by them. To review the anti-cancer effects of polyphenols, Google Scholar, PubMed and ScienceDirect were used to study the literature available. The article that have been used for literature review were filtered using keywords including cancer, polyphenols and signaling pathways. Majorly articles from the last 10 years have been considered for the review but relevant articles from earlier than 10 years have also been considered. Almost 400 articles were studied for the review and 200 articles have been cited. The current review shows the potential of polyphenols as anti-cancer compounds and how the consumption of a diet rich in polyphenols can help in the prevention of cancer. Because of their capacity to affect a variety of oncogenic and oncosuppressive signaling pathways, phytochemicals derived from plants have been effectively introduced as an alternative anticarcinogenic medicines. Graphical Abstract
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Affiliation(s)
- Kareena Moar
- Department of Biochemistry, Central University of Haryana, Mahendergarh, 123031 India
| | - Somu Yadav
- Department of Biochemistry, Central University of Haryana, Mahendergarh, 123031 India
| | - Anuja Pant
- Department of Biochemistry, Central University of Haryana, Mahendergarh, 123031 India
| | - Deepika
- Department of Biochemistry, Central University of Haryana, Mahendergarh, 123031 India
| | - Pawan Kumar Maurya
- Department of Biochemistry, Central University of Haryana, Mahendergarh, 123031 India
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2
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Mandal MK, Domb AJ. Antimicrobial Activities of Natural Bioactive Polyphenols. Pharmaceutics 2024; 16:718. [PMID: 38931842 PMCID: PMC11206801 DOI: 10.3390/pharmaceutics16060718] [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: 04/05/2024] [Revised: 05/21/2024] [Accepted: 05/24/2024] [Indexed: 06/28/2024] Open
Abstract
Secondary metabolites, polyphenols, are widespread in the entire kingdom of plants. They contain one or more hydroxyl groups that have a variety of biological functions in the natural environment. These uses include polyphenols in food, beauty products, dietary supplements, and medicinal products and have grown rapidly during the past 20 years. Antimicrobial polyphenols are described together with their sources, classes, and subclasses. Polyphenols are found in different sources, such as dark chocolate, olive oil, red wine, almonds, cashews, walnuts, berries, green tea, apples, artichokes, mushrooms, etc. Examples of benefits are antiallergic, antioxidant, anticancer agents, anti-inflammatory, antihypertensive, and antimicrobe properties. From these sources, different classes of polyphenols are helpful for the growth of internal functional systems of the human body, providing healthy fats, vitamins, and minerals, lowering the risk of cardiovascular diseases, improving brain health, and rebooting our cellular microbiome health by mitochondrial uncoupling. Among the various health benefits of polyphenols (curcumin, naringenin, quercetin, catechin, etc.) primarily different antimicrobial activities are discussed along with possible future applications. For polyphenols and antimicrobial agents to be proven safe, adverse health impacts must be substantiated by reliable scientific research as well as in vitro and in vivo clinical data. Future research may be influenced by this evaluation.
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Affiliation(s)
| | - Abraham J. Domb
- The Alex Grass Center for Drug Design & Synthesis and the Center for Cannabis Research, School of Pharmacy, Institute of Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel;
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Muchtaridi M, Az-Zahra F, Wongso H, Setyawati LU, Novitasari D, Ikram EHK. Molecular Mechanism of Natural Food Antioxidants to Regulate ROS in Treating Cancer: A Review. Antioxidants (Basel) 2024; 13:207. [PMID: 38397805 PMCID: PMC10885946 DOI: 10.3390/antiox13020207] [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: 12/02/2023] [Revised: 01/27/2024] [Accepted: 01/31/2024] [Indexed: 02/25/2024] Open
Abstract
Cancer is the second-highest mortality rate disease worldwide, and it has been estimated that cancer will increase by up to 20 million cases yearly by 2030. There are various options of treatment for cancer, including surgery, radiotherapy, and chemotherapy. All of these options have damaging adverse effects that can reduce the patient's quality of life. Cancer itself arises from a series of mutations in normal cells that generate the ability to divide uncontrollably. This cell mutation can happen as a result of DNA damage induced by the high concentration of ROS in normal cells. High levels of reactive oxygen species (ROS) can cause oxidative stress, which can initiate cancer cell proliferation. On the other hand, the cytotoxic effect from elevated ROS levels can be utilized as anticancer therapy. Some bioactive compounds from natural foods such as fruit, vegetables, herbs, honey, and many more have been identified as a promising source of natural antioxidants that can prevent oxidative stress by regulating the level of ROS in the body. In this review, we have highlighted and discussed the benefits of various natural antioxidant compounds from natural foods that can regulate reactive oxygen species through various pathways.
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Affiliation(s)
- Muchtaridi Muchtaridi
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia; (F.A.-Z.); (L.U.S.); (D.N.)
- Research Collaboration Centre for Radiopharmaceuticals Theranostic, National Research and Innovation Agency (BRIN), Jln. Raya Bandung Sumedang Km. 21, Jatinangor 45363, Indonesia;
| | - Farhah Az-Zahra
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia; (F.A.-Z.); (L.U.S.); (D.N.)
| | - Hendris Wongso
- Research Collaboration Centre for Radiopharmaceuticals Theranostic, National Research and Innovation Agency (BRIN), Jln. Raya Bandung Sumedang Km. 21, Jatinangor 45363, Indonesia;
- Research Center for Radioisotope, Radiopharmaceutical and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency (BRIN), Jl. Puspiptek, Kota Tangerang 15314, Indonesia
| | - Luthfi Utami Setyawati
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia; (F.A.-Z.); (L.U.S.); (D.N.)
- Research Collaboration Centre for Radiopharmaceuticals Theranostic, National Research and Innovation Agency (BRIN), Jln. Raya Bandung Sumedang Km. 21, Jatinangor 45363, Indonesia;
| | - Dhania Novitasari
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia; (F.A.-Z.); (L.U.S.); (D.N.)
| | - Emmy Hainida Khairul Ikram
- Integrated Nutrition Science and Therapy Research Group (INSPIRE), Faculty of Health Sciences, Universiti Teknologi MARA Cawangan Selangor, Kampus Puncak Alam, Bandar Puncak Alam 42300, Malaysia;
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Abd-Elghany AA, Mohamad EA. Chitosan-Coated Niosomes Loaded with Ellagic Acid Present Antiaging Activity in a Skin Cell Line. ACS OMEGA 2023; 8:16620-16629. [PMID: 37214686 PMCID: PMC10193557 DOI: 10.1021/acsomega.2c07254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
The polyphenol compound ellagic acid (EA) extracted from pomegranate has potential bioactivity against different types of chronic diseases. Skin aging is a long-term physiological process caused by many environmental factors, the most important of which is exposure to sun ultraviolet (UV) radiation. UV-induced chronic photodamage of the skin results in extrinsic aging. This study aimed to evaluate the photoprotective effects of EA on the human fibroblast skin cell line HFB4 and investigate its capacity to protect collagen from UV-induced deterioration. EA was encapsulated into chitosan-coated niosomes to reduce the skin aging effect of UV radiation in vitro. The tested formulations (niosomes loaded with EA and chitosan-coated niosomes loaded with EA) were characterized using transmission electron microscopy, dynamic light scattering, and scanning electron microscopy. Furthermore, the in vitro release of EA was determined. The HFB4 cell line samples were split into five groups: control, UV, UV-EA, UV-NIO-EA, and UV-CS-NIO-EA. UV irradiation was applied to the cell line groups via a UV-emitting lamp for 1 h, and then cell viability was measured for each group. The expression of genes implicated in skin aging (Co1A1, TERT, Timp3, and MMP3) was also assessed to quantify the impact of the loaded EA. The findings showed that EA-loaded chitosan-coated niosomes improved cell survival, upregulated Col1A1, TERT, and Timp3 genes, and downregulated MMP3. Thus, nanoparticles encapsulating EA are potent antioxidants that can preserve collagen levels and slow down the aging process in human skin.
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Affiliation(s)
- Amr A. Abd-Elghany
- Radiology
and Medical Imaging Department, College of Applied Medical Sciences, Prince Sattam Bin Abdul-Aziz University, Al-Kharj 11942, KSA
- Biophysics
Department, Faculty of Science, Cairo University, Cairo University St., Giza 12613, Egypt
| | - Ebtesam A. Mohamad
- Biophysics
Department, Faculty of Science, Cairo University, Cairo University St., Giza 12613, Egypt
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Duckworth C, Stutts J, Clatterbuck K, Nosoudi N. Effect of ellagic acid and retinoic acid on collagen and elastin production by human dermal fibroblasts. Biomed Mater Eng 2023; 34:473-480. [PMID: 37005874 DOI: 10.3233/bme-230007] [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] [Indexed: 04/03/2023]
Abstract
BACKGROUND Elastin is a fibrous protein key to the structure and support of skin as well as other organ tissues. Elastic fibers are located in the skin's dermal layer and make up approximately 2%-4% of the fat-free dry weight of the dermis in the skin of adults. Aging causes the progressive degradation of elastin fibers. Loss of these fibers can cause skin sagging and wrinkling, loss of healthy blood vessels and lung capacity, aneurysms, and Chronic Obstructive Pulmonary Disease (COPD). OBJECTIVE We hypothesized that ellagic acid, a polyphenol, will increase elastin in human dermal fibroblasts (HDF) due to polyphenols' elastin binding properties. METHOD We treated HDF's with 2 μg/ml ellagic acid for 28 days to see the elastin deposition in HDF cell cultures. To test this, we treated HDFs with polyphenols ellagic acid for 3, 7, 14 and 21 days. For comparison purposes, we included a group of ellagic acid and retinoic acid since retinoic acid is already in the market for elastin regeneration purposes. RESULTS When ellagic acid and retinoic acid were introduced together, insoluble elastin and collagen deposition were significantly higher in HDFs compared to other groups. CONCLUSION Polyphenols and retinoic acid can improve skin extracellular matrix production of elastin and collagen and may improve skin fine wrinkles.
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Affiliation(s)
- Chloe Duckworth
- Department of Biomedical Engineering, College of Engineering and Computer Sciences, Marshall University, Huntington, WV, USA
| | - Jada Stutts
- Department of Biomedical Engineering, College of Engineering and Computer Sciences, Marshall University, Huntington, WV, USA
| | - Kayla Clatterbuck
- Department of Biomedical Engineering, College of Engineering and Computer Sciences, Marshall University, Huntington, WV, USA
| | - Nasim Nosoudi
- Department of Biomedical Engineering, College of Engineering and Computer Sciences, Marshall University, Huntington, WV, USA
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Naeem A, Hu P, Yang M, Zhang J, Liu Y, Zhu W, Zheng Q. Natural Products as Anticancer Agents: Current Status and Future Perspectives. Molecules 2022; 27:molecules27238367. [PMID: 36500466 PMCID: PMC9737905 DOI: 10.3390/molecules27238367] [Citation(s) in RCA: 183] [Impact Index Per Article: 61.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 11/22/2022] [Accepted: 11/28/2022] [Indexed: 12/02/2022] Open
Abstract
Natural products have been an invaluable and useful source of anticancer agents over the years. Several compounds have been synthesized from natural products by modifying their structures or by using naturally occurring compounds as building blocks in the synthesis of these compounds for various purposes in different fields, such as biology, medicine, and engineering. Multiple modern and costly treatments have been applied to combat cancer and limit its lethality, but the results are not significantly refreshing. Natural products, which are a significant source of new therapeutic drugs, are currently being investigated as potential cytotoxic agents and have shown a positive trend in preclinical research and have prompted numerous innovative strategies in order to combat cancer and expedite the clinical research. Natural products are becoming increasingly important for drug discovery due to their high molecular diversity and novel biofunctionality. Furthermore, natural products can provide superior efficacy and safety due to their unique molecular properties. The objective of the current review is to provide an overview of the emergence of natural products for the treatment and prevention of cancer, such as chemosensitizers, immunotherapeutics, combinatorial therapies with other anticancer drugs, novel formulations of natural products, and the molecular mechanisms underlying their anticancer properties.
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Affiliation(s)
- Abid Naeem
- Key Laboratory of Modern Preparation of Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Pengyi Hu
- Key Laboratory of Modern Preparation of Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Ming Yang
- Key Laboratory of Modern Preparation of Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Jing Zhang
- Key Laboratory of Modern Preparation of Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Yali Liu
- Key Laboratory of Pharmacodynamics and Safety Evaluation, Health Commission of Jiangxi Province, Nanchang Medical College, Nanchang 330006, China
- Key Laboratory of Pharmacodynamics and Quality Evaluation on Anti-Inflammatory Chinese Herbs, Jiangxi Administration of Traditional Chinese Medicine, Nanchang Medical College, Nanchang 330006, China
| | - Weifeng Zhu
- Key Laboratory of Modern Preparation of Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Qin Zheng
- Key Laboratory of Modern Preparation of Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
- Correspondence:
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Velur G, Kusanur R. Herbal Drugs in Cancer Treatment. RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY 2022. [DOI: 10.1134/s1068162022060267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Phenolic-rich feijoa extracts from flesh, peel and whole fruit activate apoptosis pathways in the LNCaP cell line. Food Chem 2022; 383:132285. [PMID: 35168051 DOI: 10.1016/j.foodchem.2022.132285] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 01/25/2022] [Accepted: 01/26/2022] [Indexed: 11/22/2022]
Abstract
This study aimed to explore the potential anticancer activity of phenolic-rich feijoa extracts from the flesh, peel, and whole fruit on the human prostate cancer cell line (LNCaP). Results showed that feijoa extracts had cancer-specific anti-proliferative activity on the LNCaP cell line. The anticancer activity of feijoa extracts was shown through activation of the caspase-dependent apoptosis pathway based on the increase of sub-G1 phase in the cell cycle, the decrease of mitochondrial membrane potential, as well as the elevated caspase 3, 8, and 9 activity in the treated LNCaP cells. The anti-cancer activity of feijoa extracts could be attributed to the high total phenolic contents (0.14-0.37 mg GAE/mg dw) and, in particular, the high ellagic acid content (2.662-9.119 μg/mg dw). The successful activation of the caspase-dependent apoptosis pathway indicates that phenolic-rich feijoa extracts have a good potential to be utilized as a functional ingredient in foods and nutraceuticals.
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Li W, Swiderski K, Murphy KT, Lynch GS. Role for Plant-Derived Antioxidants in Attenuating Cancer Cachexia. Antioxidants (Basel) 2022; 11:183. [PMID: 35204066 PMCID: PMC8868096 DOI: 10.3390/antiox11020183] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 01/13/2022] [Accepted: 01/13/2022] [Indexed: 12/24/2022] Open
Abstract
Cancer cachexia is the progressive muscle wasting and weakness experienced by many cancer patients. It can compromise the response to gold standard cancer therapies, impair functional capacity and reduce overall quality of life. Cancer cachexia accounts for nearly one-third of all cancer-related deaths and has no effective treatment. The pathogenesis of cancer cachexia and its progression is multifactorial and includes increased oxidative stress derived from both the tumor and the host immune response. Antioxidants have therapeutic potential to attenuate cancer-related muscle loss, with polyphenols, a group of plant-derived antioxidants, being the most widely investigated. This review describes the potential of these plant-derived antioxidants for treating cancer cachexia.
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Affiliation(s)
| | | | | | - Gordon S. Lynch
- Centre for Muscle Research, Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC 3010, Australia; (W.L.); (K.S.); (K.T.M.)
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AbouAitah K, Allayh AK, Wojnarowicz J, Shaker YM, Swiderska-Sroda A, Lojkowski W. Nanoformulation Composed of Ellagic Acid and Functionalized Zinc Oxide Nanoparticles Inactivates DNA and RNA Viruses. Pharmaceutics 2021; 13:2174. [PMID: 34959455 PMCID: PMC8706547 DOI: 10.3390/pharmaceutics13122174] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 12/10/2021] [Accepted: 12/12/2021] [Indexed: 02/06/2023] Open
Abstract
The COVID-19 pandemic has strongly impacted daily life across the globe and caused millions of infections and deaths. No drug therapy has yet been approved for the clinic. In the current study, we provide a novel nanoformulation against DNA and RNA viruses that also has a potential for implementation against COVID-19. The inorganic-organic hybrid nanoformulation is composed of zinc oxide nanoparticles (ZnO NPs) functionalized with triptycene organic molecules (TRP) via EDC/NHS coupling chemistry and impregnated with a natural agent, ellagic acid (ELG), via non-covalent interactions. The physicochemical properties of prepared materials were identified with several techniques. The hybrid nanoformulation contained 9.5 wt.% TRP and was loaded with up to 33.3 wt.% ELG. ELG alone exhibited higher cytotoxicity than both the ZnO NPs and nanoformulation against host cells. The nanoformulation efficiently inhibited viruses, compared to ZnO NPs or ELG alone. For H1N1 and HCoV-229E (RNA viruses), the nanoformulation had a therapeutic index of 77.3 and 75.7, respectively. For HSV-2 and Ad-7 (DNA viruses), the nanoformulation had a therapeutic index of 57.5 and 51.7, respectively. In addition, the nanoformulation showed direct inactivation of HCoV-229E via a virucidal mechanism. The inhibition by this mechanism was > 60%. Thus, the nanoformulation is a potentially safe and low-cost hybrid agent that can be explored as a new alternative therapeutic strategy for COVID-19.
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Affiliation(s)
- Khaled AbouAitah
- Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska St. 29/37, 01-142 Warsaw, Poland; (J.W.); (A.S.-S.)
- Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre (NRC), 33 El–Behouth St., Dokki, Giza 12622, Egypt
| | - Abdou K. Allayh
- Environmental Virology Laboratory, Water Pollution Research Department, Environment and Climate Change Institute, National Research Centre (NRC), 33 El–Behouth St., Dokki, Giza 12622, Egypt;
| | - Jacek Wojnarowicz
- Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska St. 29/37, 01-142 Warsaw, Poland; (J.W.); (A.S.-S.)
| | - Yasser M. Shaker
- Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Institute, National Research Centre (NRC), 33 El–Behouth St., Dokki, Giza 12622, Egypt;
| | - Anna Swiderska-Sroda
- Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska St. 29/37, 01-142 Warsaw, Poland; (J.W.); (A.S.-S.)
| | - Witold Lojkowski
- Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska St. 29/37, 01-142 Warsaw, Poland; (J.W.); (A.S.-S.)
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The Separation and Purification of Ellagic Acid from Phyllanthus urinaria L. by a Combined Mechanochemical-Macroporous Resin Adsorption Method. SEPARATIONS 2021. [DOI: 10.3390/separations8100186] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Ellagic acid is a phenolic compound that exhibits both antimutagenic and anticarcinogenic activity in a wide range of assays in vitro and in vivo. It occurs naturally in some foods such as raspberries, strawberries, grapes, and black currants. In this study, a valid and reliable method based on mechanochemical-assisted extraction (MCAE) and macroporous adsorption resin was developed to extract and prepare ellagic acid from Phyllanthus urinaria L. (PUL). The MCAE parameters, acidolysis, and macroporous adsorption resin conditions were investigated. The key MCAE parameters were optimized as follows: the milling time was 5 min, the ball mill speed was 100 rpm, and the ball mill filling rate was 20.9%. Sulfuric acid with a concentration of 0.552 mol/L was applied for the acidolysis with the optimized acidolysis time of 30 min and acidolysis temperature of 40 °C. Additionally, the XDA-8D macroporous resin was chosen for the purification work. Both the static and dynamic adsorption tests were carried out. Under the optimized conditions, the yield of ellagic acid was 10.2 mg/g, and the content was over 97%. This research provided a rapid and efficient method for the preparation of ellagic acid from the cheaply and easily obtained PUL. Meanwhile, it is relatively low-cost work that can provide a technical basis for the comprehensive utilization of PUL.
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Georgieva A, Ilieva Y, Kokanova-Nedialkova Z, Zaharieva MM, Nedialkov P, Dobreva A, Kroumov A, Najdenski H, Mileva M. Redox-Modulating Capacity and Antineoplastic Activity of Wastewater Obtained from the Distillation of the Essential Oils of Four Bulgarian Oil-Bearing Roses. Antioxidants (Basel) 2021; 10:antiox10101615. [PMID: 34679750 PMCID: PMC8533594 DOI: 10.3390/antiox10101615] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 10/03/2021] [Accepted: 10/04/2021] [Indexed: 01/31/2023] Open
Abstract
The wastewater from the distillation of rose oils is discharged directly into the soil because it has a limited potential for future applications. The aim of the present study was to determine in vitro the chromatographic profile, redox-modulating capacity, and antineoplastic activity of wastewater obtained by distillation of essential oils from the Bulgarian Rosa alba L., Rosa damascena Mill., Rosa gallica L., and Rosa centifolia L. We applied UHPLC-HRMS for chromatographic analysis of rose wastewaters, studied their metal-chelating and Fe(III)-reducing ability, and performed MTT assay for the evaluation of cytotoxic potential against three tumorigenic (HEPG2-hepatocellular adenocarcinoma, A-375-malignant melanoma, A-431-non-melanoma epidermoid squamous skin carcinoma) and one non-tumorigenic human cell lines (HaCaT-immortalized keratinocytes). The median inhibitory concentrations (IC50) were calculated with nonlinear modeling using the MAPLE® platform. The potential of the wastewaters to induce apoptosis was also examined. Mono-, di-, and acylated glycosides of quercetin and kaempferol, ellagic acid and its derivatives as main chemical components, and gallic acid and its derivatives-such as catechin and epicatechin-were identified. The redox-modulating capacity of the samples (TPTZ test) showed that all four wastewaters exhibited the properties of excellent heavy metal cleaners, but did not exert very strong cytotoxic effects. The lowest IC50 rate was provided in wastewater from R. centifolia (34-35 µg/mL of gallic acid equivalents after a 72 h period for all cell lines). At 24 and 48 hours, the most resistant cell line was HEPG2, followed by HaCaT. After 72 h of exposure, the IC50 values were similar for tumor and normal cells. Still, R. damascena had a selectivity index over 2.0 regarding A-431 non-melanoma skin cancer cells, showing a good toxicological safety profile in addition to moderate activity-IC50 of 35 µg/mL polyphenols. The obtained results related to wastewaters acquired after the distillation of essential oils from the Bulgarian R. alba, R. damascena, R. gallica, and R. centifolia direct our attention to further studies for in-depth elucidation of their application as detoxifying agents under oxidative damage conditions in other experimental datasets.
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Affiliation(s)
- Almira Georgieva
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev str., 1113 Sofia, Bulgaria; (A.G.); (Y.I.); (M.M.Z.); (A.K.); (H.N.)
- Institute of Neurobiology, Bulgarian Academy of Sciences, 23 Acad. G. Bonchev str., 1113 Sofia, Bulgaria
| | - Yana Ilieva
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev str., 1113 Sofia, Bulgaria; (A.G.); (Y.I.); (M.M.Z.); (A.K.); (H.N.)
| | | | - Maya Margaritova Zaharieva
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev str., 1113 Sofia, Bulgaria; (A.G.); (Y.I.); (M.M.Z.); (A.K.); (H.N.)
| | - Paraskev Nedialkov
- Faculty of Pharmacy, Medical University of Sofia, 2 Dunav str., 1000 Sofia, Bulgaria; (Z.K.-N.); (P.N.)
| | - Ana Dobreva
- Department of Aromatic and Medicinal Plants, Institute for Roses and Aromatic Plants, 49 Osvobojdenie Blvd, 6100 Kazanlak, Bulgaria;
| | - Alexander Kroumov
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev str., 1113 Sofia, Bulgaria; (A.G.); (Y.I.); (M.M.Z.); (A.K.); (H.N.)
| | - Hristo Najdenski
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev str., 1113 Sofia, Bulgaria; (A.G.); (Y.I.); (M.M.Z.); (A.K.); (H.N.)
| | - Milka Mileva
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev str., 1113 Sofia, Bulgaria; (A.G.); (Y.I.); (M.M.Z.); (A.K.); (H.N.)
- Correspondence: ; Tel.: +35-92-979-3185
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Anjaly K, Tiku AB. MicroRNA mediated therapeutic effects of natural agents in prostate cancer. Mol Biol Rep 2021; 48:5759-5773. [PMID: 34304390 DOI: 10.1007/s11033-021-06575-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 07/15/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Several natural products, extensively studied for their anticancer activities, have been found to play an efficient role in preventing prostate cancer (PCa). Recently many natural agents have been reported to modulate microRNAs (miRNAs), that are involved in cancer cell growth. The microRNAs are endogenous small noncoding ribonucleic acid molecules that regulate various biological processes through an elegant mechanism of post-transcriptional control of gene expression. Besides being involved in cancer initiation, progression, angiogenesis, inflammation, they have been reported to be responsible for chemoresistance, and radioresistance of tumors. The dysregulated miRNA expression has been associated with many cancers including PCa. Over the past several years, it has been found that natural agents are good regulators of miRNAs and have a role in PCa also. Understanding the molecular mechanisms involving miRNAs by natural agents could result in developing useful strategies to combat this deadly disease. METHODS In order to collect research articles, the PubMed search engine was used with keywords 'prostate cancer' and 'natural agents' and 2007 papers were retrieved, further refinement with keywords 'phytochemical' and 'prostate cancer' showed 503 papers. Data was collected from research articles, published from 2010 to 2021. From these, research articles showing miRNA-mediated mechanisms were selected. RESULTS In this review, we have summarized the information available on the modulation of miRNAs by natural agents, their derivatives, and various combinatorial strategies with chemo/radiation therapy for the mitigation of PCa. CONCLUSIONS Based on the current review of literature, it has been found that the use of natural agents is a novel approach for altering miRNA expression strongly associated with PCa development, recurrence and resistance.
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Affiliation(s)
- Km Anjaly
- Radiation and Cancer Therapeutics Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India
| | - A B Tiku
- Radiation and Cancer Therapeutics Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
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Bhinge SD, Bhutkar MA, Randive DS, Wadkar GH, Todkar SS, Savali AS, Chittapurkar HR. Screening of hair growth promoting activity of Punica granatum L. (pomegranate) leaves extracts and its potential to exhibit antidandruff and anti-lice effect. Heliyon 2021; 7:e06903. [PMID: 33997417 PMCID: PMC8100084 DOI: 10.1016/j.heliyon.2021.e06903] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/15/2021] [Accepted: 04/21/2021] [Indexed: 11/27/2022] Open
Abstract
The intent of the present investigation was to explore the utility of alcoholic and aqueous extract of Punica granatum L. as hair growth promoter along with anti-lice and antidandruff activity. A filter paper diffusion approach was employed for screening of the pediculocidal and ovicidal activity. Albino mice, preselected for their telogen phase of hair growth were used during the study. The prepared extracts, Minoxidil and control were applied over shaved skin surface on to the backs of mice to assess telogen to anagen transition. The qualitative and quantitative analysis was performed. The outcome of the studies revealed that Punica granatum L. alcoholic and aqueous extracts exhibited prominent anti-lice activity. The transition of telogen to anagen phase of the number of anagen hair follicle was observed in approximately 45, 27 and 51% of animals treated with alcoholic and aqueous extract of Punica granatum L., and Minoxidil, respectively, which suggest the hair growth promoting potential of the extract of Punica granatum L. Also, 3 % Punica granatum L. alcoholic extracts exhibited a potent antidandruff activity against fungal strains tested. Maltol, was identified as a principal phytoconstituent in the alcoholic extract. The findings greatly suggest anti-lice, antidandruff and hair growth promoting potential of the extract of Punica granatum L.
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Affiliation(s)
- Somnath D Bhinge
- Department of Pharmaceutical Chemistry, Rajarambapu College of Pharmacy, Kasegaon, Maharashtra, 415 404, India
| | - Mangesh A Bhutkar
- Department of Pharmaceutics, Rajarambapu College of Pharmacy, Kasegaon, Maharashtra, 415 404, India
| | - Dheeraj S Randive
- Department of Pharmaceutics, Rajarambapu College of Pharmacy, Kasegaon, Maharashtra, 415 404, India
| | - Ganesh H Wadkar
- Department of Pharmacognosy, Rajarambapu College of Pharmacy, Kasegaon, Maharashtra, 415 404, India
| | - Sachin S Todkar
- Department of Pharmaceutical Chemistry, Rajarambapu College of Pharmacy, Kasegaon, Maharashtra, 415 404, India
| | - Anil S Savali
- Government College of Pharmacy, Karad, Maharashtra, 415124, India
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Dunn M, Mirda D, Whalen MJ, Kogan M. An integrative active surveillance of prostate cancer. Explore (NY) 2021; 18:483-487. [PMID: 33980424 DOI: 10.1016/j.explore.2021.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Accepted: 04/12/2021] [Indexed: 11/27/2022]
Affiliation(s)
- Marisa Dunn
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; George Washington University School of Medicine & Health Sciences, Washington DC, United States
| | - Danielle Mirda
- George Washington University School of Medicine & Health Sciences, Washington DC, United States
| | - Michael J Whalen
- George Washington University Medical Faculty Associates, Washington DC, United States
| | - Mikhail Kogan
- George Washington University Medical Faculty Associates, Washington DC, United States; George Washington University Center for Integrative Medicine, Washington DC, United States.
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Impact of micro wet milling process on pomegranate peel phenolics extraction using multi‐response optimization. JOURNAL OF FOOD MEASUREMENT AND CHARACTERIZATION 2021. [DOI: 10.1007/s11694-021-00853-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Bertolini FM, Morbiato G, Facco P, Marszałek K, Pérez-Esteve É, Benedito J, Zambon A, Spilimbergo S. Optimization of the supercritical CO2 pasteurization process for the preservation of high nutritional value of pomegranate juice. J Supercrit Fluids 2020. [DOI: 10.1016/j.supflu.2020.104914] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Patil M, Karhale S, Bhenki C, Kumbhar A, Helavi V. Sulfonic acid@pericarp-pomegranate: A natural supported catalyst for synthesis of bis(indolyl)alkanes. REACTION KINETICS MECHANISMS AND CATALYSIS 2020. [DOI: 10.1007/s11144-020-01828-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Rizeq B, Gupta I, Ilesanmi J, AlSafran M, Rahman MDM, Ouhtit A. The Power of Phytochemicals Combination in Cancer Chemoprevention. J Cancer 2020; 11:4521-4533. [PMID: 32489469 PMCID: PMC7255361 DOI: 10.7150/jca.34374] [Citation(s) in RCA: 88] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2019] [Accepted: 12/03/2019] [Indexed: 12/25/2022] Open
Abstract
Conventional therapies for cancer treatment have posed many challenges, including toxicity, multidrug resistance and economic expenses. In contrast, complementary alternative medicine (CAM), employing phytochemicals have recently received increased attention owing to their capability to modulate a myriad of molecular mechanisms with a less toxic effect. Increasing evidence from preclinical and clinical studies suggest that phytochemicals can favorably modulate several signaling pathways involved in cancer development and progression. Combinations of phytochemicals promote cell death, inhibit cell proliferation and invasion, sensitize cancerous cells, and boost the immune system, thus making them striking alternatives in cancer therapy. We previously investigated the effect of six phytochemicals (Indol-3-Carbinol, Resveratrol, C-phycocyanin, Isoflavone, Curcumin and Quercetin), at their bioavailable levels on breast cancer cell lines and were compared to primary cell lines over a period of 6 days. This study showed the compounds had a synergestic effect in inhibiting cell proliferation, reducing cellular migration and invasion, inducing both cell cycle arrest and apoptosis. Despite the vast number of basic science and preclinical cancer studies involving phytochemicals, the number of CAM clinical trials in cancer treatment still remains nascent. In this review, we summarize findings from preclinical and clinical studies, including our work involving use of phytochemicals, individually as well as in combination and further discuss the potential of these phytochemicals to pave way to integrate CAM in primary health care.
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Affiliation(s)
- Balsam Rizeq
- Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar
- Biomedical Research Center, Qatar University, Doha, Qatar
| | - Ishita Gupta
- College of Medicine, Qatar University, Doha, Qatar
| | - Josephine Ilesanmi
- Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar
| | - Mohammed AlSafran
- Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar
| | - MD Mizanur Rahman
- Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar
| | - Allal Ouhtit
- Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar
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Lin Z, Lin C, Fu C, Lu H, Jin H, Chen Q, Pan J. The protective effect of Ellagic acid (EA) in osteoarthritis: An in vitro and in vivo study. Biomed Pharmacother 2020; 125:109845. [PMID: 32058211 DOI: 10.1016/j.biopha.2020.109845] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 12/27/2019] [Accepted: 12/29/2019] [Indexed: 01/11/2023] Open
Abstract
Osteoarthritis (OA), a progressive joint disorder, is principally characterized by the degeneration and destruction of the articular cartilage. Ellagic acid (EA), a natural polyphenol found in berries and nuts has shown potent anti-inflammatory effects, however, its effects and underlying mechanisms on OA have seldom been systematically illuminated. In this study, we reported the anti-inflammatory effects of Ellagic acid (EA) in the progression of OA in both in vitro and in vivo experiments. in vitro study, IL-1β-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), and interleukin-6 (IL-6) were inhibited by Ellagic acid (EA). Moreover, Ellagic acid (EA) down-regulated the IL-1β-stimulated matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) while up-regulated the collagen of type II and aggrecan. Mechanistically, we revealed that Ellagic acid (EA) suppressed nuclear factor kappa B (NF-κB) signaling in IL-1β -induced chondrocytes. And Ellagic acid (EA)-induced protectiveness in OA development was also shown by the DMM model. Taken together, our data indicate that Ellagic acid (EA) may serve as a potential drug for OA treatment.
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Affiliation(s)
- Zeng Lin
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xue Yuan Xi Road, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, China; Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, Wenzhou, China
| | - Chen Lin
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xue Yuan Xi Road, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, China; Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, Wenzhou, China
| | - Changchang Fu
- Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, China; Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, Wenzhou, China
| | - Hongwei Lu
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xue Yuan Xi Road, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, China; Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, Wenzhou, China
| | - Haidong Jin
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xue Yuan Xi Road, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, China; Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, Wenzhou, China
| | - Qin Chen
- Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
| | - Jun Pan
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xue Yuan Xi Road, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, China; Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, Wenzhou, China.
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Ding C, Bi H, Wang D, Kang M, Tian Z, Zhang Y, Wang H, Zhu T, Ma J. Preparation of Chitosan/Alginate-ellagic Acid Sustained-release Microspheres and their Inhibition of Preadipocyte Adipogenic Differentiation. Curr Pharm Biotechnol 2020; 20:1213-1222. [PMID: 31762423 DOI: 10.2174/1389201020666190809110511] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 05/05/2019] [Accepted: 08/01/2019] [Indexed: 12/17/2022]
Abstract
OBJECTIVE In this study, chitosan/alginate-ellagic acid sustained-release microspheres were prepared, and the effect of sustained-release microspheres on preadipocyte adipogenic differentiation was analyzed. METHODS Chitosan/alginate-ellagic acid microspheres were prepared and identified by scanning electron microscopy (SEM) and infrared spectroscopy (IR). The drug release rates were measured at pH 6.8, 7.0, 7.2, 7.4 to determine sustained release of ellagic acid from microspheres. The effects of 0.1, 1, 10 mg/L chitosan/alginate-ellagic acid microsphere on 3T3-F442A preadipocyte proliferation were determined by Methyl thiazolyl tetrazolium assay (MTT), and cell morphology was checked by hematoxylin/ eosin staining (HE staining). The effect of chitosan/alginate-ellagic acid microspheres on preadipocyte adipogenic differentiation was also determined by Oil red O staining, and lipogenesis was measured by isopropanol extraction. The molecular mechanism was investigated by detecting the mRNA expression of CCAAT/enhancer binding protein alpha (C/EBPα) and peroxisome proliferatorsactivated receptor gamma (PPARγ). RESULTS Chitosan/alginate-ellagic acid sustained-release microspheres were successfully prepared, and the inhibition of proliferation and adipogenic differentiation of preadipocytes was found to be dosedependent. The mechanism of differentiation inhibition was found to be closely related to the expression of transcription factor C/EBPα and PPARγ. CONCLUSION Chitosan/alginate can be used as a good material to prepare ellagic acid sustained-release microspheres, and these microspheres can be used for treating the obesity.
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Affiliation(s)
- Chengshi Ding
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China.,Tianjin Institute of Environmental Medicine & Operational Medicine, Tianjin 300050, China
| | - Haidan Bi
- College of Food Science and Pharmaceutical Engineering, Zaozhuang University, Zaozhuang 277160, China
| | - Deya Wang
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China
| | - Meiling Kang
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China
| | - Zhongjing Tian
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China
| | - Yingxia Zhang
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China
| | - Hongkai Wang
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China
| | - Tianshun Zhu
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China
| | - Jing Ma
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China.,Basic Medical School, Jining Medical College, Jining 272067, China
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Multi-enzymatic Systems Immobilized on Chitosan Beads for Pomegranate Juice Treatment in Fluidized Bed Reactor: Effect on Haze-Active Molecules and Chromatic Properties. FOOD BIOPROCESS TECH 2019. [DOI: 10.1007/s11947-019-02315-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Nguyen Thanh H, Thi Huyen N, Van Khanh N, Kim Thu D, Thanh Tung B. Phytochemicals and antidiabetic activity of the aqueous extract of the Punica granatum fruit in streptozotocin-induced diabetic mice. J Basic Clin Physiol Pharmacol 2019; 30:jbcpp-2019-0061. [PMID: 33581010 DOI: 10.1515/jbcpp-2019-0061] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 05/02/2019] [Indexed: 06/12/2023]
Abstract
The present study investigated the phytochemicals and antidiabetic effect of the aqueous extract of the fruit of Punica granatum Linn. in streptozotocin (STZ)-induced diabetic mice. The fruit of P. granatum was extracted with water. The phytochemicals of the water extract were investigated by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The water extract of P. granatum at doses of 150 and 300 mg/kg body weight (bw) was administered to mice for 21 days, and blood glucose level, triglyceride, total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein-cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme were estimated. Analyzed phytochemicals showed the fruit of P. granatum Linn has a high amount of phenolic and flavonoid compounds, which provide beneficial effect for this plant. The oral administration of the fruit extract of P. granatum at doses of 150 and 300 mg/kg bw for 21 days significantly reduced blood glucose level, triglycerides, serum cholesterol, LDL-cholesterol, AST and ALT enzyme. Our results suggested that the fruit extract of P. granatum has strong antidiabetic effect in STZ-induced diabetic mice. The fruit of this plant might be a potential source of drug for treatment of diabetes.
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Affiliation(s)
- Hai Nguyen Thanh
- School of Medicine and Pharmacy, Vietnam National University Hanoi, Hanoi, Vietnam
| | - Nguyen Thi Huyen
- School of Medicine and Pharmacy, Vietnam National University Hanoi, Hanoi, Vietnam
| | - Nguyen Van Khanh
- School of Medicine and Pharmacy, Vietnam National University Hanoi, Hanoi, Vietnam
| | - Dang Kim Thu
- Department of Pharmacology and Clinical Pharmacology, School of Medicine and Pharmacy, Vietnam National University Hanoi, Hanoi, Vietnam
| | - Bui Thanh Tung
- Department of Pharmacology and Clinical Pharmacology, School of Medicine and Pharmacy, Vietnam National University Hanoi, Hanoi, Vietnam
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Herranz-López M, Losada-Echeberría M, Barrajón-Catalán E. The Multitarget Activity of Natural Extracts on Cancer: Synergy and Xenohormesis. MEDICINES (BASEL, SWITZERLAND) 2018; 6:E6. [PMID: 30597909 PMCID: PMC6473537 DOI: 10.3390/medicines6010006] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 12/18/2018] [Accepted: 12/24/2018] [Indexed: 12/12/2022]
Abstract
It is estimated that over 60% of the approved drugs and new drug developments for cancer and infectious diseases are from natural origin. The use of natural compounds as a potential source of antitumor agents has been deeply studied in many cancer models, both in vitro and in vivo. Most of the Western medicine studies are based on the use of highly selective pure compounds with strong specificity for their targets such as colchicine or taxol. Nevertheless, approximately 60% of fairly specific drugs in their initial research fail because of toxicity or ineffectiveness in late-stage preclinical studies. Moreover, cancer is a multifaceted disease that in most cases deserves a polypharmacological therapeutic approach. Complex plant-derived mixtures such as natural extracts are difficult to characterize and hardly exhibit high pharmacological potency. However, in some cases, these may provide an advantage due to their multitargeted mode of action and potential synergistic behavior. The polypharmacology approach appears to be a plausible explanation for the multigargeted mechanism of complex natural extracts on different proteins within the same signalling pathway and in several biochemical pathways at once. This review focuses on the different aspects of natural extracts in the context of anticancer activity drug development, with special attention to synergy studies and xenohormesis.
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Affiliation(s)
- María Herranz-López
- Instituto de Biología Molecular y Celular (IBMC) and Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández 03202 Elche, Spain.
| | - María Losada-Echeberría
- Instituto de Biología Molecular y Celular (IBMC) and Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández 03202 Elche, Spain.
| | - Enrique Barrajón-Catalán
- Instituto de Biología Molecular y Celular (IBMC) and Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández 03202 Elche, Spain.
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Reichert CL, Silva DB, Carollo CA, Weffort-Santos AM, Santos CAM. Metabolic profiling and correlation analysis for the determination of killer compounds of proliferating and clonogenic HRT-18 colon cancer cells from Lafoensia pacari. JOURNAL OF ETHNOPHARMACOLOGY 2018; 224:541-552. [PMID: 29928972 DOI: 10.1016/j.jep.2018.06.021] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 06/14/2018] [Accepted: 06/15/2018] [Indexed: 06/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Lafoensia pacari A. St.-Hil., belonging to the family Lythraceae and popularly known as 'dedaleira' and 'mangava-brava,' is a native tree of the Brazilian Cerrado, and its barks have been traditionally used as a tonic to treat inflammatory conditions, particularly related to gastric ulcers, wounds or fevers and various types of cancer. AIM OF THE STUDY We have previously demonstrated the apoptogenic effects of the methanolic extract of L. pacari using various cancer cell lines. In the present study, this extract has been partitioned into fractions to identify the components that might be responsible for the apoptogenic effects using HRT-18 cells, which have been previously demonstrated to be sensitive to this extract. MATERIALS AND METHODS A standard methanolic extract was prepared and fractionated by centrifugal partition chromatography. The fractions were submitted to cytotoxicity and clonogenic assays to monitor the effects in parallel with LC-DAD-MS and statistical analyses to suggest the potential bioactive compounds. RESULTS Besides ellagic acid, the primary constituent of the plant and also the biomarker of the species, punicalin, pedunculagin and punicalagin isomers, catechin and ellagic acid derivatives were putatively identified. CONCLUSIONS The barks of L. pacari are rich in ellagic acid and various hydrolysable tannins, some of which were reported for the first time in this species, such as punicalagin and ellagitannins. This mixture of substances had the ability to kill proliferating cells and abrogate the growth of clonogenic cells in a similar manner shown by the methanolic extract of our previous study. The collective data reported herein suggest that the biological activities of the L. pacari barks used by population to treat cancer conditions are due to the apoptogenic effects promoted by a mixed content of ellagitannins.
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Affiliation(s)
- Cristiane Loiva Reichert
- Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Paraná, Curitiba, PR, Brazil
| | - D B Silva
- Laboratório de Produtos Naturais e Espectrometria de Massas, Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição, Universidade Federal do Mato Grosso do Sul, Campo Grande, MS, Brazil
| | - Carlos Alexandre Carollo
- Laboratório de Produtos Naturais e Espectrometria de Massas, Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição, Universidade Federal do Mato Grosso do Sul, Campo Grande, MS, Brazil
| | - Almeriane Maria Weffort-Santos
- Departamento de Análises Clínicas, Licity of Lafoensia pacari preparations and fractions on HRaboratório de Hematologia, Universidade Federal do Paraná, Curitiba, PR, Brazil
| | - C A M Santos
- Departamento de Farmácia, Laboratório de Farmacognosia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
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Iranshahy M, Iranshahi M, Abtahi SR, Karimi G. The role of nuclear factor erythroid 2-related factor 2 in hepatoprotective activity of natural products: A review. Food Chem Toxicol 2018; 120:261-276. [DOI: 10.1016/j.fct.2018.07.024] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 07/11/2018] [Accepted: 07/12/2018] [Indexed: 12/15/2022]
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Elucidation of interaction mechanism of ellagic acid to the integrin linked kinase. Int J Biol Macromol 2018; 122:1297-1304. [PMID: 30227205 DOI: 10.1016/j.ijbiomac.2018.09.089] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 09/13/2018] [Accepted: 09/14/2018] [Indexed: 12/20/2022]
Abstract
Integrin-linked kinase (ILK) is a member of Ser/Thr kinase which interacts to the cytoplasmic domain of β-integrins, and thereby induces apoptosis. ILK is considered as potential drug target because it's direct involvement in the tumor progression. Here, we have performed molecular docking followed by 100 ns MD simulation to understand the mechanism of interaction of ILK with the ellagic acid (EA). EA is well known for its antiproliferative and antioxidant properties in cancer cell lines and animal models. We have observed that EA binds to the active site cavity of ILK and causes conformational changes in the ILK structure. The orientation of EA in the active pocket of ILK showed to have least RMSD values and stable. The average binding energy ILK-EA complex calculated during MMPBSA was -191.267 kJ/mol, indicating a relatively strong binding affinity. The actual binding affinity of EA to ILK was measured by fluorescence spectroscopy and Kb and n values were 9.28 μM and 1.9264 (~2), respectively. The IC50 values for EA were 26.22 ± 0.12 μM for MCF-7 and 38.45 ± 2.42 μM for HepG2 cells, estimated by MTT assay. Our findings are helpful to design EA-based novel inhibitors of ILK which have potential to attenuate tumor progression.
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Huang Z, Delparastan P, Burch P, Cheng J, Cao Y, Messersmith PB. Injectable dynamic covalent hydrogels of boronic acid polymers cross-linked by bioactive plant-derived polyphenols. Biomater Sci 2018; 6:2487-2495. [PMID: 30069570 PMCID: PMC6107875 DOI: 10.1039/c8bm00453f] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 05/09/2018] [Indexed: 12/20/2022]
Abstract
We report here the development of hydrogels formed at physiological conditions using PEG (polyethylene glycol) based polymers modified with boronic acids (BAs) as backbones and the plant derived polyphenols ellagic acid (EA), epigallocatechin gallate (EGCG), tannic acid (TA), nordihydroguaiaretic acid (NDGA), rutin trihydrate (RT), rosmarinic acid (RA) and carminic acid (CA) as linkers. Rheological frequency sweep and single molecule force spectroscopy (SMFS) experiments show that hydrogels linked with EGCG and TA are mechanically stiff, arising from the dynamic covalent bond formed by the polyphenol linker and boronic acid functionalized polymer. Stability tests of the hydrogels in physiological conditions revealed that gels linked with EA, EGCG, and TA are stable. We furthermore showed that EA- and EGCG-linked hydrogels can be formed via in situ gelation in pH 7.4 buffer, and provide long-term steady state release of bioactive EA. In vitro experiments showed that EA-linked hydrogel significantly reduced the viability of CAL-27 human oral cancer cells via gradual release of EA.
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Affiliation(s)
- Zhuojun Huang
- Department of Materials Science and Engineering
, University of California
, Berkeley
,
Berkeley
, CA
94720-1760
, USA
.
| | - Peyman Delparastan
- Department of Materials Science and Engineering
, University of California
, Berkeley
,
Berkeley
, CA
94720-1760
, USA
.
| | - Patrick Burch
- Department of Bioengineering
, University of California
, Berkeley
,
Berkeley
, CA
94720-1760
, USA
| | - Jing Cheng
- Department of Bioengineering
, University of California
, Berkeley
,
Berkeley
, CA
94720-1760
, USA
| | - Yi Cao
- Department of Physics
, Nanjing University
,
Nanjing
, 210093
, China PR
| | - Phillip B. Messersmith
- Department of Materials Science and Engineering
, University of California
, Berkeley
,
Berkeley
, CA
94720-1760
, USA
.
- Department of Bioengineering
, University of California
, Berkeley
,
Berkeley
, CA
94720-1760
, USA
- Materials Science Division
, Lawrence Berkeley National Laboratory
,
Berkeley
, CA
, USA
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Zeb A. Ellagic acid in suppressing in vivo and in vitro oxidative stresses. Mol Cell Biochem 2018; 448:27-41. [PMID: 29388153 DOI: 10.1007/s11010-018-3310-3] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Accepted: 01/27/2018] [Indexed: 01/20/2023]
Abstract
Oxidative stress is a biological condition produced by a variety of factors, causing several chronic diseases. Oxidative stress was, therefore, treated with natural antioxidants, such as ellagic acid (EA). EA has a major role in protecting against different diseases associated with oxidative stress. This review critically discussed the antioxidant role of EA in biological systems. The in vitro and in vivo studies have confirmed the protective role of EA in suppressing oxidative stress. The review also discussed the mechanism of EA in suppressing of oxidative stress, which showed that EA activates specific endogenous antioxidant enzymes and suppresses specific genes responsible for inflammation, diseases, or disturbance of biochemical systems. The amount of EA used and duration, which plays a significant role in the treatment of oxidative stress has been discussed. In conclusion, EA is a strong natural antioxidant, which possesses the suppressing power of oxidative stress in biological systems.
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Affiliation(s)
- Alam Zeb
- Laboratory of Biochemistry, Department of Biotechnology, University of Malakand, Chakdara, Lower Dir, Khyber Pakhtunkhwa, Pakistan.
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30
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Wang Y, Zeng Y, Fu W, Zhang P, Li L, Ye C, Yu L, Zhu X, Zhao S. Seed-mediated growth of Au@Ag core-shell nanorods for the detection of ellagic acid in whitening cosmetics. Anal Chim Acta 2017; 1002:97-104. [PMID: 29306418 DOI: 10.1016/j.aca.2017.11.067] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 11/16/2017] [Accepted: 11/27/2017] [Indexed: 01/01/2023]
Abstract
Seed-mediated growth has been employed as a simple and powerful means to the shape-controlled synthesis of metal nanocrystals. In this work, we apply the principle of seed-mediated growth in analytical chemistry, and achieve improved sensitivity due to the low energy barrier in the target-induced formation of bimetallic nanoparticles with core-shell structure. As a result, a simple, reliable, highly sensitive and selective method for the detection of ellagic acid (EA), a naturally occurring polyphenolic antioxidant, has been developed. With the aid of EA in alkaline solution, Ag+ ions can be transformed to Ag atoms and deposit on the surfaces of Au nanorods (AuNRs, act as seeds here) to generate Au@Ag core-shell nanorods, accompanied by blue shift of the longitudinal localized surface plasmon resonance (LSPR) band of AuNRs from near-infrared region to shorter wavelengths. Based on the linear relationship between the wavelength change of longitudinal LSPR band and the concentration of EA, our method achieves a detectable range of 0.2-20 μM and a limit of detection as low as 40 nM toward EA. This approach is highlighted by its high sensitivity for EA assay, which benefits from the viewpoint of thermodynamics in the nucleation/growth mode of metal nanoparticles. Moreover, this method shows high selectivity for EA detection when potential species coexist, and thus has been successfully applied in the detection of EA in skin-whitening cosmetics. The proposed strategy of seed-mediated growth herein can also be extended to other systems for sensing.
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Affiliation(s)
- Yi Wang
- Chongqing Key Laboratory of Green Synthesis and Applications, College of Chemistry, Chongqing Normal University, Chongqing 401331, PR China.
| | - Yang Zeng
- Chongqing Key Laboratory of Green Synthesis and Applications, College of Chemistry, Chongqing Normal University, Chongqing 401331, PR China
| | - Wensheng Fu
- Chongqing Key Laboratory of Green Synthesis and Applications, College of Chemistry, Chongqing Normal University, Chongqing 401331, PR China
| | - Pu Zhang
- Research Center of Pharmacodynamics Evaluation Engineering Technology of Chongqing, College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China.
| | - Ling Li
- Chongqing Key Laboratory of Green Synthesis and Applications, College of Chemistry, Chongqing Normal University, Chongqing 401331, PR China
| | - Cuiying Ye
- Chongqing Key Laboratory of Green Synthesis and Applications, College of Chemistry, Chongqing Normal University, Chongqing 401331, PR China
| | - Lan Yu
- Chongqing Key Laboratory of Green Synthesis and Applications, College of Chemistry, Chongqing Normal University, Chongqing 401331, PR China
| | - Xiaochun Zhu
- Chongqing Key Laboratory of Green Synthesis and Applications, College of Chemistry, Chongqing Normal University, Chongqing 401331, PR China
| | - Song Zhao
- Chongqing Key Laboratory of Green Synthesis and Applications, College of Chemistry, Chongqing Normal University, Chongqing 401331, PR China
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31
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Pavlova EL, Simeonova LS, Gegova GA. Combined efficacy of oseltamivir, isoprinosine and ellagic acid in influenza A(H3N2)-infected mice. Biomed Pharmacother 2017; 98:29-35. [PMID: 29241072 DOI: 10.1016/j.biopha.2017.12.014] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Revised: 11/30/2017] [Accepted: 12/04/2017] [Indexed: 11/25/2022] Open
Abstract
Influenza pathogenesis comprises a complex cascade of impaired cellular processes resulting from the viral replication and exaggerated immune response accompanied by reactive oxygen species (ROS) burst and oxidative stress, destructing membranous structures and tissues. By classical virological and biochemical methods we compared and evaluated the therapeutic effects of 2.5mg/kg/day of the antiviral drug - oseltamivir (OS), 500mg/kg/day of the immune modulator - isoprinosine (IP) and 500mg/kg/day of the antioxidant agent ellagic acid (EA) with a focus on their combined activities in influenza H3N2 virus-infected mice. The survival, lung pathology and titers, as well as the oxidative stress biomarker thiobarbituric acid reactive substances (TBARS) in the lungs, liver and blood plasma, correlated to the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione reductase (GR) were assessed. We found that the viral inhibitor applied together with the immune modulator and the antioxidant exhibited strong therapeutic effects on the survival of the influenza-challenged mice. That effect was mostly pronounced for the triple combination - protection index (PI) of 75.2%, mean survival time (MST) extended by 5.8 days compared to the PBS control and significant reduction of the lung titers by 1.38 Δlg; 2.3 scores lower lung pathology and 8 times reduction of the accumulated TBARS in the lungs and liver on the 5-th day p.i. The enzymatic assays revealed that this combination demonstrated very good protection against the damaging superoxide radicals (83% efficiency of SOD, in comparison to healthy controls 100%). The double combinations of OS with IP and EA also showed protective effects according to the virological analysis - PI of 53.1% and 54.5%. Ten times higher GR activity was observed when the combination EA+OS and monotherapy of EA were applied (96% in comparison to healthy controls 100%). The best antioxidant effect in blood plasma was observed in the EA+IP group - 4 times reduction in the TBARS-content compared to infected controls but it did not have any efficacy on the survival and lung injury.
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Affiliation(s)
- Elitsa L Pavlova
- Biophysics & Medical Physics, Sofia University "St. Kliment Ohridski", 5 James Boucher Blvd., 1164, Sofia, Bulgaria.
| | - Lora S Simeonova
- Department of Virology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Georgi Bonchev Str., 1113, Sofia, Bulgaria
| | - Galina A Gegova
- Department of Virology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Georgi Bonchev Str., 1113, Sofia, Bulgaria
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Wang H, Zhang Y, Tian Z, Ma J, Kang M, Ding C, Ming D. Preparation of β-CD-Ellagic Acid Microspheres and Their Effects on HepG2 Cell Proliferation. Molecules 2017; 22:molecules22122175. [PMID: 29292740 PMCID: PMC6149914 DOI: 10.3390/molecules22122175] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 11/29/2017] [Accepted: 12/06/2017] [Indexed: 01/17/2023] Open
Abstract
OBJECTIVE In this study, β-cyclodextrin (β-CD) was chosen as the coating for ellagic acid to prepare ellagic acid microspheres, and the effect of microspheres on the growth of HepG2 cells was observed. METHODS Scanning electron microscopy, infrared spectroscopy, and release rate analysis were used to identify the formation of ellagic acid microspheres. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the effect of different concentrations of ellagic acid microspheres on tumor cell proliferation at 6, 12, 24 and 36 h, and cell morphology and quantity were observed using hematoxylin-eosin (HE) staining. Single-cell gel electrophoresis was used to observe the effect of ellagic acid microspheres on the DNA damage of HepG2 cells, and the Olive tail moment and the mRNA expression of tumor suppressor protein gene p53 was measured. RESULTS β-CD could be used as wrapping material of ellagic acid to prepare ellagic acid microspheres. HepG2 cell proliferation could be inhibited by 0.1, 0.3 and 0.5 g/L of ellagic acid microspheres in a dose- and time-dependent manner, and the mechanism of proliferation inhibition was related to DNA damage and cell apoptosis. CONCLUSION Preparing ellagic acid microspheres with β-CD is feasible, and ellagic acid microspheres have potential therapeutic value (anticancer).
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Affiliation(s)
- Hongkai Wang
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China.
| | - Yingxia Zhang
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China.
| | - Zhongjing Tian
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China.
| | - Jing Ma
- College of Medical Science, Zaozhuang Vocational College, Zaozhuang 277800, China.
| | - Meiling Kang
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China.
| | - Chengshi Ding
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China.
| | - Dongfeng Ming
- College of Life Science, Zaozhuang University, Zaozhuang 277160, China.
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Gabriele E, Brambilla D, Ricci C, Regazzoni L, Taguchi K, Ferri N, Asai A, Sparatore A. New sulfurated derivatives of cinnamic acids and rosmaricine as inhibitors of STAT3 and NF-κB transcription factors. J Enzyme Inhib Med Chem 2017; 32:1012-1028. [PMID: 28738705 PMCID: PMC6009881 DOI: 10.1080/14756366.2017.1350658] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 06/30/2017] [Accepted: 06/30/2017] [Indexed: 12/30/2022] Open
Abstract
A set of new sulfurated drug hybrids, mainly derived from caffeic and ferulic acids and rosmaricine, has been synthesized and their ability to inhibit both STAT3 and NF-κB transcription factors have been evaluated. Results showed that most of the new hybrid compounds were able to strongly and selectively bind to STAT3, whereas the parent drugs were devoid of this ability at the tested concentrations. Some of them were also able to inhibit the NF-κB transcriptional activity in HCT-116 cell line and inhibited HCT-116 cell proliferation in vitro with IC50 in micromolar range, thus suggesting a potential anticancer activity. Taken together, our study described the identification of new derivatives with dual STAT3/NF-κB inhibitory activity, which may represent hit compounds for developing multi-target anticancer agents.
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Affiliation(s)
- Elena Gabriele
- Department of Pharmaceutical Sciences, Università degli Studi di Milano, Milano, Italy
| | - Dario Brambilla
- Department of Pharmaceutical Sciences, Università degli Studi di Milano, Milano, Italy
| | - Chiara Ricci
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy
| | - Luca Regazzoni
- Department of Pharmaceutical Sciences, Università degli Studi di Milano, Milano, Italy
| | - Kyoko Taguchi
- Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
| | - Nicola Ferri
- Department of Pharmaceutical and Pharmacological Sciences, Università degli Studi di Padova, Largo Egidio Meneghetti, Padova, Italy
| | - Akira Asai
- Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
| | - Anna Sparatore
- Department of Pharmaceutical Sciences, Università degli Studi di Milano, Milano, Italy
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34
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Cerreti M, Liburdi K, Benucci I, Emiliani Spinelli S, Lombardelli C, Esti M. Optimization of pectinase and protease clarification treatment of pomegranate juice. Lebensm Wiss Technol 2017. [DOI: 10.1016/j.lwt.2017.04.022] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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35
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Mouhid L, Corzo-Martínez M, Torres C, Vázquez L, Reglero G, Fornari T, Ramírez de Molina A. Improving In Vivo Efficacy of Bioactive Molecules: An Overview of Potentially Antitumor Phytochemicals and Currently Available Lipid-Based Delivery Systems. JOURNAL OF ONCOLOGY 2017; 2017:7351976. [PMID: 28555156 PMCID: PMC5438845 DOI: 10.1155/2017/7351976] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 03/06/2017] [Indexed: 02/07/2023]
Abstract
Cancer is among the leading causes of morbidity and mortality worldwide. Many of the chemotherapeutic agents used in cancer treatment exhibit cell toxicity and display teratogenic effect on nontumor cells. Therefore, the search for alternative compounds which are effective against tumor cells but reduce toxicity against nontumor ones is of great importance in the progress or development of cancer treatments. In this sense, scientific knowledge about relevant aspects of nutrition intimately involved in the development and progression of cancer progresses rapidly. Phytochemicals, considered as bioactive ingredients present in plant products, have shown promising effects as potential therapeutic/preventive agents on cancer in several in vitro and in vivo assays. However, despite their bioactive properties, phytochemicals are still not commonly used in clinical practice due to several reasons, mainly attributed to their poor bioavailability. In this sense, new formulation strategies are proposed as carriers to improve their bioefficacy, highlighting the use of lipid-based delivery systems. Here, we review the potential antitumoral activity of the bioactive compounds derived from plants and the current studies carried out in animal and human models. Furthermore, their association with lipids as a formulation strategy to enhance their efficacy in vivo is also reported. The development of high effective bioactive supplements for cancer treatment based on the improvement of their bioavailability goes through this association.
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Affiliation(s)
- Lamia Mouhid
- Molecular Oncology and Nutritional Genomics of Cancer, IMDEA Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Marta Corzo-Martínez
- Department of Production and Characterization of Novel Foods, Institute of Food Science Research (CIAL), Campus of International Excellence (CEI) UAM+CSIC, 28049 Madrid, Spain
| | - Carlos Torres
- Department of Production and Characterization of Novel Foods, Institute of Food Science Research (CIAL), Campus of International Excellence (CEI) UAM+CSIC, 28049 Madrid, Spain
| | - Luis Vázquez
- Department of Production and Characterization of Novel Foods, Institute of Food Science Research (CIAL), Campus of International Excellence (CEI) UAM+CSIC, 28049 Madrid, Spain
| | - Guillermo Reglero
- Molecular Oncology and Nutritional Genomics of Cancer, IMDEA Food Institute, CEI UAM+CSIC, Madrid, Spain
- Department of Production and Characterization of Novel Foods, Institute of Food Science Research (CIAL), Campus of International Excellence (CEI) UAM+CSIC, 28049 Madrid, Spain
| | - Tiziana Fornari
- Department of Production and Characterization of Novel Foods, Institute of Food Science Research (CIAL), Campus of International Excellence (CEI) UAM+CSIC, 28049 Madrid, Spain
| | - Ana Ramírez de Molina
- Molecular Oncology and Nutritional Genomics of Cancer, IMDEA Food Institute, CEI UAM+CSIC, Madrid, Spain
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36
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Rustagi Y, Jain A, Saxena S, Rani V. Natural Polyphenols as Prospective Inhibitors for MMPs Remodeling in Human Diseases. PROTEASES IN HUMAN DISEASES 2017:263-283. [DOI: 10.1007/978-981-10-3162-5_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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37
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Punica granatum peel: an organocatalyst for green and rapid synthesis of 3,4-dihydropyrimidin-2 (1H)-ones/thiones under solvent-free condition. RESEARCH ON CHEMICAL INTERMEDIATES 2016. [DOI: 10.1007/s11164-016-2828-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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38
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Sahebkar A, Gurban C, Serban A, Andrica F, Serban MC. Effects of supplementation with pomegranate juice on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2016; 23:1095-1102. [PMID: 26922037 DOI: 10.1016/j.phymed.2015.12.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Revised: 12/05/2015] [Accepted: 12/08/2015] [Indexed: 06/05/2023]
Abstract
BACKGROUND Pomegranate juice (PJ) has a high content of antioxidants and bioactive polyphenols, being widely used for its antioxidant, anti-inflammatory and chemopreventive effects. PURPOSE The objective of this meta-analysis consisted in investigating the impact of PJ on plasma C-reactive protein (CRP) concentrations. METHODS The search included SCOPUS, Medline and two Iranian bibliographic databases namely MagIran and Scientific Information Database (from inception to December 09, 2014) to identify prospective trials for investigating the impact of pomegranate preparations on serum concentrations of CRP. Two independent reviewers extracted data on study characteristics, methods and outcomes. RESULTS Among 427 participants in the selected studies, 216 were allocated to PJ groups, and 211 to control group. Meta-analysis of data from 5 eligible randomized controlled trials (RCTs) arms did not provide compelling evidence as to a significant CRP-lowering effect of supplementation with pomegranate juice (WMD: -0.22 mg/l, 95% CI: -0.45, 0.01, p = 0.061). The impact of pomegranate juice on plasma CRP levels was found to be independent of duration of supplementation (slope: 0.003; 95% CI: -0.005, 0.011; p = 0.444). CONCLUSION In conclusion, this meta-analysis of data from 5 prospective trials did not indicate a significant effect of PJ on plasma CRP levels, and this effect was independent of duration of supplementation.
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Affiliation(s)
- Amirhossein Sahebkar
- Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia
| | - Camelia Gurban
- Department of Biochemistry and Pharmacology, Discipline of Biochemistry, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania.
| | - Alexandru Serban
- Department Automation and Applied Informatics, University Politehnica Timisoara, Romania
| | - Florina Andrica
- Faculty of Pharmacy, Discipline of Pharmaceutical Chemistry, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
| | - Maria-Corina Serban
- Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Functional Sciences, Discipline of Pathophysiology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
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39
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Zhou B, Wang J, Zheng G, Qiu Z. Methylated urolithin A, the modified ellagitannin-derived metabolite, suppresses cell viability of DU145 human prostate cancer cells via targeting miR-21. Food Chem Toxicol 2016; 97:375-384. [PMID: 27725205 DOI: 10.1016/j.fct.2016.10.005] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Revised: 07/13/2016] [Accepted: 10/06/2016] [Indexed: 01/20/2023]
Abstract
Urolithins are bioactive ellagic acid-derived metabolites produced by human colonic microflora. Although previous studies have demonstrated the cytotoxicity of urolithins, the effect of urolithins on miRNAs is still unclear. In this study, the suppressing effects of methylated urolithin A (mUA) on cell viability in human prostate cancer DU145 cells was investigated. mUA induced caspase-dependent cell apoptosis, mitochondrial depolarization and down-regulation of Bcl-2/Bax ratio. The results showed that upon exposure to mUA, miR-21 expression was decreased and the expression of PTEN and Pdcd4 protein was elevated. mUA could further suppress Akt phosphorylation and increase protein expression of FOXO3a, and the effects of mUA on Akt phosphorylation and protein expression of FOXO3a were blocked by PTEN silence. Moreover, mUA suppressed the Wnt/β-catenin-mediated transcriptional activation of MMP-7 and c-Myc, and this function of mUA on MMP-7 and c-Myc was attenuated by over-expression of miR-21. In conclusion, our data suggest that mUA can suppress cell viability in DU145 cells through modulating miR-21 and its downstream series-wound targets, including PTEN, Akt and Wnt/β-catenin signaling.
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Affiliation(s)
- Benhong Zhou
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China
| | - Jing Wang
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China
| | - Guohua Zheng
- Key Laboratory of Chinese Medicine Resource and Compound Prescription (Ministry of Education), Hubei University of Chinese Medicine, Wuhan 430065, People's Republic of China
| | - Zhenpeng Qiu
- College of Pharmacy, Hubei University of Chinese Medicine, No. 1, West Huangjiahu Road, Wuhan 430065, People's Republic of China.
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40
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Pavlova EL, Zografov NN, Simeonova LS. Comparative study on the antioxidant capacities of synthetic influenza inhibitors and ellagic acid in model systems. Biomed Pharmacother 2016; 83:755-762. [PMID: 27479194 DOI: 10.1016/j.biopha.2016.07.046] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 07/09/2016] [Accepted: 07/21/2016] [Indexed: 11/17/2022] Open
Abstract
This study compares the antioxidant capacities in vitro of several synthetic and natural compounds applied and researched for influenza treatment - oseltamivir, isoprinosine, ellagic acid, vitamin E and vitamin C. Three chemical systems are utilized for the generation of reactive oxygen species (ROS) at pH 7.4 and pH 8.5: (1) Fenton's (Fe2++H2O2) for OH and -OH species (2) H2O2 (3) NADH-phenazinemethosulfat, for superoxide radicals (O2-). The kinetics was evaluated by lucigenin-enhanced chemiluminescence. The calculated constants of inhibition k7 describe the antioxidant capacity at the moment of oxidative burst. Their values do not necessarily correspond to the calculated total antioxidant activity. The obtained results revealed that the synthetic anti-influenza drugs (oseltamivir and isoprinosine) as well as ellagic acid possess pronounced scavenging properties mostly against superoxide radicals, comparable and higher than that of traditional natural antioxidants. Quantitative analysis of the antioxidant effects of the examined synthetic substances was performed. The results compared the corresponding effect of the average physiological concentrations and the applied therapeutic antioxidant dose. With these experiments we registered new aspects of their therapeutic activities, due to antioxidant properties against hydroxyl, superoxide radicals and H2O2 oxidation.
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Affiliation(s)
- Elitsa L Pavlova
- Biophysics & Medical Physics, Sofia University "St. Kliment Ohridski", 5 James Boucher Blvd., 1164 Sofia, Bulgaria.
| | - Nikolay N Zografov
- Biophysics & Medical Physics, Sofia University "St. Kliment Ohridski", 5 James Boucher Blvd., 1164 Sofia, Bulgaria
| | - Lora S Simeonova
- Department of Virology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Georgi Bonchev Str., 1113 Sofia, Bulgaria
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41
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Functional Properties of Punica granatum L. Juice Clarified by Hollow Fiber Membranes. Processes (Basel) 2016. [DOI: 10.3390/pr4030021] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Saha P, Yeoh BS, Singh R, Chandrasekar B, Vemula PK, Haribabu B, Vijay-Kumar M, Jala VR. Gut Microbiota Conversion of Dietary Ellagic Acid into Bioactive Phytoceutical Urolithin A Inhibits Heme Peroxidases. PLoS One 2016; 11:e0156811. [PMID: 27254317 PMCID: PMC4890745 DOI: 10.1371/journal.pone.0156811] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 05/19/2016] [Indexed: 12/15/2022] Open
Abstract
Numerous studies signify that diets rich in phytochemicals offer many beneficial functions specifically during pathologic conditions, yet their effects are often not uniform due to inter-individual variation. The host indigenous gut microbiota and their modifications of dietary phytochemicals have emerged as factors that greatly influence the efficacy of phytoceutical-based intervention. Here, we investigated the biological activities of one such active microbial metabolite, Urolithin A (UA or 3,8-dihydroxybenzo[c]chromen-6-one), which is derived from the ellagic acid (EA). Our study demonstrates that UA potently inhibits heme peroxidases i.e. myeloperoxidase (MPO) and lactoperoxidase (LPO) when compared to the parent compound EA. In addition, chrome azurol S (CAS) assay suggests that EA, but not UA, is capable of binding to Fe3+, due to its catechol-like structure, although its modest heme peroxidase inhibitory activity is abrogated upon Fe3+-binding. Interestingly, UA-mediated MPO and LPO inhibition can be prevented by innate immune protein human NGAL or its murine ortholog lipocalin 2 (Lcn2), implying the complex nature of host innate immunity-microbiota interactions. Spectral analysis indicates that UA inhibits heme peroxidase-catalyzed reaction by reverting the peroxidase back to its inactive native state. In support of these in vitro results, UA significantly reduced phorbol myristate acetate (PMA)-induced superoxide generation in neutrophils, however, EA failed to block the superoxide generation. Treatment with UA significantly reduced PMA-induced mouse ear edema and MPO activity compared to EA treated mice. Collectively, our results demonstrate that microbiota-mediated conversion of EA to UA is advantageous to both host and microbiota i.e. UA-mediated inhibition of pro-oxidant enzymes reduce tissue inflammation, mitigate non-specific killing of gut bacteria, and abrogate iron-binding property of EA, thus providing a competitive edge to the microbiota in acquiring limiting nutrient iron and thrive in the gut.
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Affiliation(s)
- Piu Saha
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America
| | - Beng San Yeoh
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America
| | - Rajbir Singh
- Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America
| | - Bhargavi Chandrasekar
- Institute for Stem Cell Biology and Regenerative Medicine (inStem), UAS-GKVK Campus, Bellary Road, Bangalore, Karnataka, India
| | - Praveen Kumar Vemula
- Institute for Stem Cell Biology and Regenerative Medicine (inStem), UAS-GKVK Campus, Bellary Road, Bangalore, Karnataka, India
- Ramalingaswami ReEntry Fellow, Dept. of Biotechnology, Govt. of India
| | - Bodduluri Haribabu
- Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America
| | - Matam Vijay-Kumar
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America
- Department of Medicine, The Pennsylvania State University Medical Center, Hershey, Pennsylvania, United States of America
- * E-mail: (MVK); (VRJ)
| | - Venkatakrishna R. Jala
- Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America
- * E-mail: (MVK); (VRJ)
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Hu S, Wang H, Han W, Ma Y, Shao Z, Li L. Development of Double-Layer Active Films Containing Pomegranate Peel Extract for the Application of Pork Packaging. J FOOD PROCESS ENG 2016. [DOI: 10.1111/jfpe.12388] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Shuaifeng Hu
- College of Food Science and Technology; Shanghai Ocean University; Shanghai 201306 China
| | - Haili Wang
- College of Food Science and Technology; Shanghai Ocean University; Shanghai 201306 China
| | - Weiyue Han
- College of Food Science and Technology; Shanghai Ocean University; Shanghai 201306 China
| | - Yichao Ma
- College of Food Science and Technology; Shanghai Ocean University; Shanghai 201306 China
| | - Zehuai Shao
- College of Food Science and Technology; Shanghai Ocean University; Shanghai 201306 China
| | - Li Li
- College of Food Science and Technology; Shanghai Ocean University; Shanghai 201306 China
- Engineering Research Center of Food Thermal-Processing Technology; Shanghai China
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Zanini S, Marzotto M, Giovinazzo F, Bassi C, Bellavite P. Effects of dietary components on cancer of the digestive system. Crit Rev Food Sci Nutr 2016; 55:1870-85. [PMID: 24841279 DOI: 10.1080/10408398.2012.732126] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Cancer is the second leading cause of death in developed countries and poor diet and physical inactivity are major risk factors in cancer-related deaths. Therefore, interventions to reduce levels of smoking, improve diet, and increase physical activity must become much higher priorities in the general population's health and health care systems. The consumption of fruit and vegetables exerts a preventive effect towards cancer and in recent years natural dietary agents have attracted great attention in the scientific community and among the general public. Foods, such as tomatoes, olive oil, broccoli, garlic, onions, berries, soy bean, honey, tea, aloe vera, grapes, rosemary, basil, chili peppers, carrots, pomegranate, and curcuma contain active components that can influence the initiation and the progression of carcinogenesis, acting on pathways implied in cell proliferation, apoptosis and metastasis. The present review illustrates the main foods and their active components, including their antioxidant, cytotoxic, and pro-apoptotic properties, with a particular focus on the evidence related to cancers of the digestive system.
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Affiliation(s)
- Sara Zanini
- a Laboratory of Translational Surgery, Universitary Laboratories of Medical Research (LURM), G. B. Rossi Hospital , University of Verona , Verona , Italy
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Avachat AM, Patel VG. Self nanoemulsifying drug delivery system of stabilized ellagic acid-phospholipid complex with improved dissolution and permeability. Saudi Pharm J 2015; 23:276-89. [PMID: 26106276 PMCID: PMC4475819 DOI: 10.1016/j.jsps.2014.11.001] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2014] [Accepted: 11/11/2014] [Indexed: 11/26/2022] Open
Abstract
Ellagic acid (EA), a plant polyphenol known for its wide-range of health benefits has limited use due to its low oral bioavailability. In this study, a new self-nanoemulsifying drug delivery system (SNEDDS), based on the phospholipid complex technique, was developed to improve the oral bioavailability of ellagic acid. Ellagic acid-phospholipid complex was prepared by an anti-solvent method and characterized. Enhanced lipophilicity after the formation of ellagic acid-phospholipid complex was verified through solubility studies. Preliminary screening was carried out to select oil, surfactant and co-surfactant. Ternary phase diagrams were constructed to identify the area of nanoemulsification. Formulations were optimized on the basis of globule size, cloud point and robustness to dilution. The optimized SNEDDS of ellagic acid-phospholipid complex showed mean globule size of 106 ± 0.198 nm and cloud point at 83-85 °C. The in vitro drug release from SNEDDS was found to be higher compared to EA suspension and complex, while ex vivo studies showed increased permeation from SNEDDS compared to EA suspension. Moreover, SNEDDS overcome the food effect which was shown by EA suspension. Thus, SNEDDS were found to be influential in improving the release performance of EA, indicating their potential to improve the oral bioavailability of EA.
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Affiliation(s)
- Amelia M. Avachat
- Department of Pharmaceutics, Sinhgad Technical Education Society’s Post Graduate Research Centre, Sinhgad College of Pharmacy, Vadgaon (Bk.), Pune 411041, India
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Sánchez-González C, Ciudad CJ, Izquierdo-Pulido M, Noé V. Urolithin A causes p21 up-regulation in prostate cancer cells. Eur J Nutr 2015; 55:1099-112. [PMID: 25962506 DOI: 10.1007/s00394-015-0924-z] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Accepted: 05/05/2015] [Indexed: 12/28/2022]
Abstract
PURPOSE Walnuts contain several bioactive compounds, including pedunculagin, a polyphenol metabolized by microbiota to form urolithins, namely urolithin A (UA). The aim of this study was to determine gene expression changes in prostate cancer cells after incubation with UA. METHODS We performed a genomic analysis to study the effect of UA on LNCaP prostate cells. Cells were incubated with 40 µM UA for 24 h, and RNA was extracted and hybridized to Affymetrix Human Genome U219 array. Microarray results were analyzed using GeneSpring v13 software. Differentially expressed genes (p < 0.05, fold change > 2) were used to perform biological association networks. Cell cycle was analyzed by flow cytometry and apoptosis measured by the rhodamine method and by caspases 3 and 7 activation. Cell viability was determined by MTT assay. RESULTS We identified two nodes, FN-1 and CDKN1A, among the differentially expressed genes upon UA treatment. CDKN1A was validated, its mRNA and protein levels were significantly up-regulated, and the promoter activation measured by luciferase. Cell cycle analysis showed an increase in G1-phase, and we also observed an induction of apoptosis and caspases 3 and 7 activation upon UA treatment. CONCLUSION Our results indicate a potential role of UA as a chemopreventive agent for prostate cancer.
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Affiliation(s)
| | - Carlos J Ciudad
- Biochemistry and Molecular Biology Department, School of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain.
| | - Maria Izquierdo-Pulido
- Nutrition and Food Science Department, University of Barcelona, 08028, Barcelona, Spain.,CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Barcelona, Spain
| | - Véronique Noé
- Biochemistry and Molecular Biology Department, School of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain
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Dietary polyphenols in prevention and treatment of prostate cancer. Int J Mol Sci 2015; 16:3350-76. [PMID: 25654230 PMCID: PMC4346900 DOI: 10.3390/ijms16023350] [Citation(s) in RCA: 126] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Revised: 01/21/2015] [Accepted: 01/26/2015] [Indexed: 02/06/2023] Open
Abstract
Prostate cancer is the most prevalent disease affecting males in many Western countries, with an estimated 29,480 deaths in 2014 in the US alone. Incidence rates for prostate cancer deaths have been decreasing since the early 1990s in men of all races/ethnicities, though they remain about 60% higher in African Americans than in any other group. The relationship between dietary polyphenols and the prevention of prostate cancer has been examined previously. Although results are sometimes inconsistent and variable, there is a general agreement that polyphenols hold great promise for the future management of prostate cancer. Various dietary components, including polyphenols, have been shown to possess anti-cancer properties. Generally considered as non-toxic, dietary polyphenols act as key modulators of signaling pathways and are therefore considered ideal chemopreventive agents. Besides possessing various anti-tumor properties, dietary polyphenols also contribute to epigenetic changes associated with the fate of cancer cells and have emerged as potential drugs for therapeutic intervention. Polyphenols have also been shown to affect post-translational modifications and microRNA expressions. This article provides a systematic review of the health benefits of selected dietary polyphenols in prostate cancer, especially focusing on the subclasses of polyphenols, which have a great effect on disease prevention and treatment.
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48
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Pitchakarn P, Chewonarin T, Ogawa K, Suzuki S, Asamoto M, Takahashi S, Shirai T, Limtrakul P. Ellagic acid inhibits migration and invasion by prostate cancer cell lines. Asian Pac J Cancer Prev 2015; 14:2859-63. [PMID: 23803044 DOI: 10.7314/apjcp.2013.14.5.2859] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Polyphenolic compounds from pomegranate fruit extracts (PFEs) have been reported to possess antiproliferative, pro-apoptotic, anti-inflammatory and anti-invasion effects in prostate and other cancers. However, the mechanisms responsible for the inhibition of cancer invasion remain to be clarified. In the present study, we investigated anti-invasive effects of ellagic acid (EA) in androgen-independent human (PC-3) and rat (PLS10) prostate cancer cell lines in vitro. The results indicated that non-toxic concentrations of EA significantly inhibited the motility and invasion of cells examined in migration and invasion assays. The EA treatment slightly decreased secretion of matrix metalloproteinase (MMP)-2 but not MMP-9 from both cell lines. We further found that EA significantly reduced proteolytic activity of collagenase/gelatinase secreted from the PLS-10 cell line. Collagenase IV activity was also concentration-dependently inhibited by EA. These results demonstrated that EA has an ability to inhibit invasive potential of prostate cancer cells through action on protease activity.
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Affiliation(s)
- Pornsiri Pitchakarn
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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49
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Lantzouraki DZ, Sinanoglou VJ, Zoumpoulakis PG, Glamočlija J, Ćirić A, Soković M, Heropoulos G, Proestos C. Antiradical–antimicrobial activity and phenolic profile of pomegranate (Punica granatum L.) juices from different cultivars: a comparative study. RSC Adv 2015. [DOI: 10.1039/c4ra11795f] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Pomegranate juices from the fruits of the two relatively new Greek cultivars “Persephone” and “Porphiroyeneti” were studied compared to the “Wonderful” cultivar.
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Affiliation(s)
- Dimitra Z. Lantzouraki
- Food Chemistry Laboratory
- Department of Chemistry
- National and Kapodistrian University of Athens
- Athens
- Greece
| | - Vassilia J. Sinanoglou
- Instrumental Food Analysis Laboratory
- Department of Food Technology
- Technological Educational Institution of Athens
- Egaleo
- Greece
| | - Panagiotis G. Zoumpoulakis
- Institute of Biology
- Medicinal Chemistry & Biotechnology
- National Hellenic Research Foundation
- Athens
- Greece
| | - Jasmina Glamočlija
- University of Belgrade
- Department of Plant Physiology
- Institute for Biological Research “Siniša Stanković”
- 11000 Belgrade
- Serbia
| | - Ana Ćirić
- University of Belgrade
- Department of Plant Physiology
- Institute for Biological Research “Siniša Stanković”
- 11000 Belgrade
- Serbia
| | - Marina Soković
- University of Belgrade
- Department of Plant Physiology
- Institute for Biological Research “Siniša Stanković”
- 11000 Belgrade
- Serbia
| | - George Heropoulos
- Institute of Biology
- Medicinal Chemistry & Biotechnology
- National Hellenic Research Foundation
- Athens
- Greece
| | - Charalampos Proestos
- Food Chemistry Laboratory
- Department of Chemistry
- National and Kapodistrian University of Athens
- Athens
- Greece
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50
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Lee JH, Won JH, Choi JM, Cha HH, Jang YJ, Park S, Kim HG, Kim HC, Kim DK. Protective effect of ellagic acid on concanavalin A-induced hepatitis via toll-like receptor and mitogen-activated protein kinase/nuclear factor κB signaling pathways. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2014; 62:10110-10117. [PMID: 25238033 DOI: 10.1021/jf503188c] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
Ellagic acid (EA) is present in certain fruits and nuts, including raspberries, pomegranates, and walnuts, and has anti-inflammatory and antioxidant properties. The aims of this study were to examine the protective effect of EA on concanavalin A (Con A)-induced hepatitis and to elucidate its underlying molecular mechanisms in mice. Mice were orally administered EA at different doses before the intravenous delivery of Con A; the different experimental groups were as follows: (i) vehicle control, (ii) Con A alone without EA, (iii) EA at 50 mg/kg, (iv) EA at 100 mg/kg, and (v) EA at 200 mg/kg. We found that EA pretreatment significantly reduced the levels of plasma aminotransferase and liver necrosis in Con A-induced hepatitis. Also, EA significantly decreased the expression levels of the toll-like receptor 2 (TLR2) and TLR4 mRNA and protein in liver tissues. Further, EA decreased the phosphorylation of JNK, ERK1/2, and p38. EA-treated groups showed suppressions of nuclear factor κB (NF-κB) and IκB-α degradation levels in liver tissues. In addition, EA pretreatment decreased the expression of pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β). These results suggest that EA protects against T-cell-mediated hepatitis through TLR and mitogen-activated protein kinase (MAPK)/NF-κB signaling pathways.
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Affiliation(s)
- Jae Hong Lee
- Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University , 221 Huksuk-Dong, Dongjak-Ku, Seoul 156-756, South Korea
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