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1
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Cuadrado A, Cazalla E, Bach A, Bathish B, Naidu SD, DeNicola GM, Dinkova-Kostova AT, Fernández-Ginés R, Grochot-Przeczek A, Hayes JD, Kensler TW, León R, Liby KT, López MG, Manda G, Shivakumar AK, Hakomäki H, Moerland JA, Motohashi H, Rojo AI, Sykiotis GP, Taguchi K, Valverde ÁM, Yamamoto M, Levonen AL. Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases. Redox Biol 2025; 81:103569. [PMID: 40059038 PMCID: PMC11970334 DOI: 10.1016/j.redox.2025.103569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Revised: 02/13/2025] [Accepted: 02/24/2025] [Indexed: 03/22/2025] Open
Abstract
Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-activated transcription factor regulating cellular defense against oxidative stress, thereby playing a pivotal role in maintaining cellular homeostasis. Its dysregulation is implicated in the progression of a wide array of human diseases, making NRF2 a compelling target for therapeutic interventions. However, challenges persist in drug discovery and safe targeting of NRF2, as unresolved questions remain especially regarding its context-specific role in diseases and off-target effects. This comprehensive review discusses the dualistic role of NRF2 in disease pathophysiology, covering its protective and/or destructive roles in autoimmune, respiratory, cardiovascular, and metabolic diseases, as well as diseases of the digestive system and cancer. Additionally, we also review the development of drugs that either activate or inhibit NRF2, discuss main barriers in translating NRF2-based therapies from bench to bedside, and consider the ways to monitor NRF2 activation in vivo.
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Affiliation(s)
- Antonio Cuadrado
- Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
| | - Eduardo Cazalla
- Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Anders Bach
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark
| | - Boushra Bathish
- Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK
| | - Sharadha Dayalan Naidu
- Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK
| | - Gina M DeNicola
- Department of Metabolism and Physiology, H. Lee. Moffitt Cancer Center, Tampa, FL, 33612, USA
| | - Albena T Dinkova-Kostova
- Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK
| | - Raquel Fernández-Ginés
- Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Anna Grochot-Przeczek
- Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
| | - John D Hayes
- Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK
| | - Thomas W Kensler
- Translational Research Program, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA
| | - Rafael León
- Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), 28007, Madrid, Spain
| | - Karen T Liby
- Indiana University School of Medicine, Department of Medicine, W. Walnut Street, Indianapolis, IN, 46202, USA
| | - Manuela G López
- Department of Pharmacology, School of Medicine, Universidad Autónoma Madrid, Madrid, Spain; Instituto de Investigación Sanitario (IIS-IP), Hospital Universitario de La Princesa, Madrid, Spain; Instituto Teófilo Hernando, Madrid, Spain
| | - Gina Manda
- Radiobiology Laboratory, Victor Babes National Institute of Pathology, Bucharest, Romania
| | | | - Henriikka Hakomäki
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
| | - Jessica A Moerland
- Indiana University School of Medicine, Department of Medicine, W. Walnut Street, Indianapolis, IN, 46202, USA
| | - Hozumi Motohashi
- Department of Medical Biochemistry, Graduate School of Medicine Tohoku University, Sendai, Japan; Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Ana I Rojo
- Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | | | - Keiko Taguchi
- Laboratory of Food Chemistry, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan; Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Ángela M Valverde
- Instituto de Investigaciones Biomédicas "Sols-Morreale" UAM-CSIC, Instituto de Investigación Sanitaria La Paz (IdiPaz), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain
| | - Masayuki Yamamoto
- Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Anna-Liisa Levonen
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
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Chen JG, Zhu YR, Qian GS, Wang JB, Lu JH, Kensler TW, Jacobson LP, Muñoz A, Groopman JD. Fifty Years of Aflatoxin Research in Qidong, China: A Celebration of Team Science to Improve Public Health. Toxins (Basel) 2025; 17:79. [PMID: 39998096 PMCID: PMC11860843 DOI: 10.3390/toxins17020079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 02/04/2025] [Accepted: 02/06/2025] [Indexed: 02/26/2025] Open
Abstract
The Qidong Liver Cancer Institute (QDLCI) and the Qidong Cancer Registry were established in 1972 with input from doctors, other medical practitioners, and non-medical investigators arriving from urban centers such as Shanghai and Nanjing. Medical teams were established to quantify the extent of primary liver cancer in Qidong, a corn-growing peninsula on the north side of the Yangtze River. High rates of liver cancer were documented and linked to several etiologic agents, including aflatoxins. Local corn, the primary dietary staple, was found to be consistently contaminated with high levels of aflatoxins, and bioassays using this corn established its carcinogenicity in ducks and rats. Observational studies noted a positive association between levels of aflatoxin in corn and incidence of liver cancer across townships. Biomarker studies measuring aflatoxin B1 and its metabolite aflatoxin M1 in biofluids reflected the exposures. Approaches to decontamination of corn from aflatoxins were also studied. In 1993, investigators from Johns Hopkins University were invited to visit the QDLCI to discuss chemoprevention studies in some townships. A series of placebo-controlled clinical trials were conducted using oltipraz (a repurposed drug), chlorophyllin (an over-the-counter drug), and beverages prepared from 3-day-old broccoli sprouts (rich in the precursor phytochemical for sulforaphane). Modulation of biomarkers of aflatoxin DNA and albumin adducts established proof of principle for the efficacy of these agents in enhancing aflatoxin detoxication. Serendipitously, by 2012, aflatoxin exposures quantified using biomarker measurements documented a many hundred-fold reduction. In turn, the Cancer Registry documents that the age-standardized incidence rate of liver cancer is now 75% lower than that seen in the 1970s. This reduction is seen in Qidongese who have never received the hepatitis B vaccination. Aflatoxin mitigation driven by economic changes switched the dietary staple of contaminated corn to rice coupled with subsequent dietary diversity leading to lower aflatoxin exposures. This 50-year effort to understand the etiology of liver cancer in Qidong provides the strongest evidence for aflatoxin mitigation as a public health strategy for reducing liver cancer burden in exposed, high-risk populations. Also highlighted are the challenges and successes of international team science to solve pressing public health issues.
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Affiliation(s)
- Jian-Guo Chen
- Department of Epidemiology, Qidong Liver Cancer Institute, Qidong People’s Hospital, Affiliated Qidong Hospital of Nantong University, Qidong 226200, China; (Y.-R.Z.); (J.-B.W.); (J.-H.L.)
| | - Yuan-Rong Zhu
- Department of Epidemiology, Qidong Liver Cancer Institute, Qidong People’s Hospital, Affiliated Qidong Hospital of Nantong University, Qidong 226200, China; (Y.-R.Z.); (J.-B.W.); (J.-H.L.)
| | - Geng-Sun Qian
- Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai 200032, China;
| | - Jin-Bing Wang
- Department of Epidemiology, Qidong Liver Cancer Institute, Qidong People’s Hospital, Affiliated Qidong Hospital of Nantong University, Qidong 226200, China; (Y.-R.Z.); (J.-B.W.); (J.-H.L.)
| | - Jian-Hua Lu
- Department of Epidemiology, Qidong Liver Cancer Institute, Qidong People’s Hospital, Affiliated Qidong Hospital of Nantong University, Qidong 226200, China; (Y.-R.Z.); (J.-B.W.); (J.-H.L.)
| | - Thomas W. Kensler
- Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA;
| | - Lisa P. Jacobson
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; (L.P.J.); (A.M.)
| | - Alvaro Muñoz
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; (L.P.J.); (A.M.)
| | - John D. Groopman
- Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA;
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Sweet MJ, Ramnath D, Singhal A, Kapetanovic R. Inducible antibacterial responses in macrophages. Nat Rev Immunol 2025; 25:92-107. [PMID: 39294278 DOI: 10.1038/s41577-024-01080-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/05/2024] [Indexed: 09/20/2024]
Abstract
Macrophages destroy bacteria and other microorganisms through phagocytosis-coupled antimicrobial responses, such as the generation of reactive oxygen species and the delivery of hydrolytic enzymes from lysosomes to the phagosome. However, many intracellular bacteria subvert these responses, escaping to other cellular compartments to survive and/or replicate. Such bacterial subversion strategies are countered by a range of additional direct antibacterial responses that are switched on by pattern-recognition receptors and/or host-derived cytokines and other factors, often through inducible gene expression and/or metabolic reprogramming. Our understanding of these inducible antibacterial defence strategies in macrophages is rapidly evolving. In this Review, we provide an overview of the broad repertoire of antibacterial responses that can be engaged in macrophages, including LC3-associated phagocytosis, metabolic reprogramming and antimicrobial metabolites, lipid droplets, guanylate-binding proteins, antimicrobial peptides, metal ion toxicity, nutrient depletion, autophagy and nitric oxide production. We also highlight key inducers, signalling pathways and transcription factors involved in driving these different antibacterial responses. Finally, we discuss how a detailed understanding of the molecular mechanisms of antibacterial responses in macrophages might be exploited for developing host-directed therapies to combat antibiotic-resistant bacterial infections.
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Affiliation(s)
- Matthew J Sweet
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
| | - Divya Ramnath
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
| | - Amit Singhal
- Infectious Diseases Labs (ID Labs), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore
| | - Ronan Kapetanovic
- INRAE, Université de Tours, Infectiologie et Santé Publique (ISP), Nouzilly, France
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Joković N, Pešić S, Vitorović J, Bogdanović A, Sharifi-Rad J, Calina D. Glucosinolates and Their Hydrolytic Derivatives: Promising Phytochemicals With Anticancer Potential. Phytother Res 2025; 39:1035-1089. [PMID: 39726346 DOI: 10.1002/ptr.8419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 10/29/2024] [Accepted: 12/10/2024] [Indexed: 12/28/2024]
Abstract
Recent research has increasingly focused on phytochemicals as promising anticancer agents, with glucosinolates (GSLs) and their hydrolytic derivatives playing a central role. These sulfur-containing compounds, found in plants of the Brassicales order, are converted by myrosinase enzymes into biologically active products, primarily isothiocyanates (ITCs) and indoles, which exhibit significant anticancer properties. Indole-3-carbinol, diindolylmethane, sulforaphane (SFN), phenethyl isothiocyanate (PEITC), benzyl isothiocyanate, and allyl isothiocyanate have shown potent anticancer effects in animal models, particularly in breast, prostate, lung, melanoma, bladder, hepatoma, and gastrointestinal cancers. Clinical studies further support the chemopreventive effects of SFN and PEITC, particularly in detoxifying carcinogens and altering biochemical markers in cancer patients. These compounds have demonstrated good bioavailability, low toxicity, and minimal adverse effects, supporting their potential therapeutic application. Their anticancer mechanisms include the modulation of reactive oxygen species, suppression of cancer-related signaling pathways, and direct interaction with tumor cell proteins. Additionally, semi-synthetic derivatives of GSLs have been developed to enhance anticancer efficacy. In conclusion, GSLs and their derivatives offer significant potential as both chemopreventive and therapeutic agents, warranting further clinical investigation to optimize their application in cancer treatment.
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Affiliation(s)
- Nataša Joković
- Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš, Niš, Serbia
| | - Strahinja Pešić
- Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš, Niš, Serbia
| | - Jelena Vitorović
- Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš, Niš, Serbia
| | - Andrija Bogdanović
- Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš, Niš, Serbia
| | - Javad Sharifi-Rad
- Universidad Espíritu Santo, Samborondón, Ecuador
- Department of Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, Craiova, Romania
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5
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Danish Rizvi SM, Abu Lila AS, Moin A, Khafagy ES, Rajab AAH, Hegazy WAH, Bendary MM. Sulforaphane Is Not Only a Food Supplement: It Diminishes the Intracellular Survival and Colonization of Salmonella enterica. ACS OMEGA 2025; 10:2969-2977. [PMID: 39895767 PMCID: PMC11780411 DOI: 10.1021/acsomega.4c09408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 01/05/2025] [Accepted: 01/10/2025] [Indexed: 02/04/2025]
Abstract
Sulforaphane is a main bioactive component in several edible cruciferous vegetables. It acquires several benefits to health in addition to its considered antibacterial and antivirulence activities. Herein, we aimed at evaluating the antivirulence activity of sulforaphane against the worldwide clinically important enteric pathogen Salmonella enterica serovar Typhimurium. The influence of sulforaphane on bacterial adhesion, invasion, biofilm formation, and intracellular replication was assayed. Additionally, the effect of sulforaphane on the type III secretion system (TTSS) in S. enterica was quantified. The outcome of the combination with different antibiotics was assessed, and an in vivo protection assay was conducted to assess the influence on S. enterica pathogenesis. The results showed the significant antibiofilm activity of sulforaphane at subinhibitory effect in addition to its significant reduction in bacterial invasion and intracellular replication inside the host cells. The in vivo findings emphasized the decreased capacity of S. enterica to induce pathogenesis in the presence of sulforaphane. Our finding attributed these antivirulence activities to the interference of sulforaphane with TTSS-type II and the downregulation of its encoding genes. In a nutshell, the edible cruciferous vegetable bioactive sulforaphane is a safe adjunct therapy that can be administrated alongside traditional antibiotics for treating clinically significant enteric pathogens as S. enterica.
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Affiliation(s)
- Syed Mohd Danish Rizvi
- Department
of Pharmaceutics, College of Pharmacy, University
of Ha’il, Ha’il 81442, Saudi Arabia
- Medical
and Diagnostic Research Center, University
of Ha’il, Ha’il 81442, Saudi Arabia
| | - Amr Selim Abu Lila
- Department
of Pharmaceutics, College of Pharmacy, University
of Ha’il, Ha’il 81442, Saudi Arabia
- Medical
and Diagnostic Research Center, University
of Ha’il, Ha’il 81442, Saudi Arabia
| | - Afrasim Moin
- Department
of Pharmaceutics, College of Pharmacy, University
of Ha’il, Ha’il 81442, Saudi Arabia
- Medical
and Diagnostic Research Center, University
of Ha’il, Ha’il 81442, Saudi Arabia
| | - El-Sayed Khafagy
- Department
of Pharmaceutics, College of Pharmacy, Prince
Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
- Department
of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
| | - Azza A. H. Rajab
- Department
of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Wael A. H. Hegazy
- Department
of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Mahmoud M. Bendary
- Department
of Microbiology and Immunology, Faculty of Pharmacy, Port Said University, Port Said 42511, Egypt
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Wei R, Pan X, Cai D, Pan L. Synergistic Inhibition of Breast Carcinoma Cell Proliferation by Quercetin and Sulforaphane via Activation of the ERK/MAPK Pathway. Cell Biochem Biophys 2025:10.1007/s12013-024-01662-6. [PMID: 39760839 DOI: 10.1007/s12013-024-01662-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/23/2024] [Indexed: 01/07/2025]
Abstract
In the contemporary era of drug discovery, herbal treatments have demonstrated an unparalleled ability to produce anticancer drugs. An important part of the therapy of cancer is the use of plants and their by-products via analogues, which alter the tumor microenvironment and several signaling pathways. The objective of the current investigation was to conclude the rate at which the herbal medications quercetin (QT) and sulforaphane (SFN) repressed the growth of breast carcinoma cells in MDA-MB-231 by preventing the ERK/MAPK signaling systems. The cells were assessed for several studies after being subjected to different concentrations (0-70 µM) of QT and SFN (QT + SFN) for duration of 24 h. We investigated the combination that QT + SFN generated cytotoxicity using the MTT assay. The DCFH-DA staining technique was utilized to assess ROS. The protein spectra of survival of cells, cell cycle progression, and apoptosis were evaluated employing flow cytometry and western blotting. The consequences illustrated that the relative cytotoxicity of QT and SFN was roughly 28.74 μM and 39.87 μM for MDA-MB-231 cells, respectively. Following the 24-h incubation period, MDA-MB-231 cells exhibit considerable cytotoxicity when QT and SFN are combined, with IC50 values of 19.48 μM. Moreover, MCF-7 and MDA-MB-231 cells treated with QT and SFN concurrently showed substantial production of ROS and increased apoptotic signals. Consequently, because QT + SFN inhibit the production of ERK/MAPK/JNK/p38-based control of proliferation and cell cycle-regulating proteins, it has been considered a chemotherapeutic medication. To determine the extent to which the co-treatment induces apoptosis, more in vivo study will be required before they can be used commercially.
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Affiliation(s)
- Ranmei Wei
- Department of Breast Diseases, Hospital of Traditional Chinese Medicine of Qiqihar, Qiqihar, Heilongjiang, China
| | - Xingchen Pan
- Department of the 0perating Room,Huaian Hospital of Huaian City, Huaian Cancer Hospital, Huaian, Jiangsu, China
| | - Danni Cai
- Outpatient Department, General hospital of the western theater command of Chinese people's liberation army, Chengdu, Sichuan, China
| | - Lili Pan
- Pharmacy Administration Office, The Third Hospital of Nanchang City, Jiangxi Province, Nanchang, Jiangxi, China.
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Ge Y, Ge Z, Tian F, Tai X, Chen D, Sun S, Shi Z, Yin J, Wei G, Li D, Wang L, Xu W, Tong M, Liu F, Zhao L, Qian X, Ge X. Sulforaphane potentiates the efficacy of chemoradiotherapy in glioblastoma by selectively targeting thioredoxin reductase 1. Cancer Lett 2024; 611:217429. [PMID: 39725145 DOI: 10.1016/j.canlet.2024.217429] [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: 08/19/2024] [Revised: 12/22/2024] [Accepted: 12/23/2024] [Indexed: 12/28/2024]
Abstract
Chemoradiotherapy is a conventional treatment modality for patients with glioblastoma (GBM). However, the efficacy of this approach is significantly hindered by the development of therapeutic resistance. The thioredoxin system, which plays a crucial role in maintaining redox homeostasis, confers protection to cancer cells against apoptosis induced by chemoradiotherapy. Herein, we demonstrate that sulforaphane (SFN), an isothiocyanate phytochemical with anti-cancer effects, inhibits the activity of thioredoxin reductase 1 (TrxR1) through covalent conjugation with residues C59/64/497&U498. This inhibition of TrxR1 leads to the accumulation of reactive oxygen species (ROS), thereby enhancing chemoradiotherapy-induced apoptosis in GBM cells. Furthermore, SFN-induced ROS accumulation facilitates the polarization of M1-like macrophages, which synergistically sensitize GBM tumors to chemoradiotherapy. In conclusion, our study unveils that SFN has potential benefits in improving the effect of chemoradiotherapy and prognosis for GBM patients by targeting TrxR1.
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Affiliation(s)
- Yuqian Ge
- Department of Nutrition and Food Hygiene, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
| | - Zehe Ge
- Department of Nutrition and Food Hygiene, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
| | - Fuwei Tian
- Department of Nutrition and Food Hygiene, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
| | - Xiaoyu Tai
- Department of Nutrition and Food Hygiene, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
| | - Dongyin Chen
- Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China
| | - Shuhong Sun
- Department of Nutrition and Food Hygiene, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
| | - Zhumei Shi
- Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Jianxing Yin
- Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Guining Wei
- Department of Pharmacology, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, China
| | - Dongmei Li
- Department of Pharmacology, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, China
| | - Lude Wang
- Department of Neurosurgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, China
| | - Wenxia Xu
- Central Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, China
| | - Minfeng Tong
- Department of Neurosurgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, China
| | - Fang Liu
- Department of Neurosurgery, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China
| | - Lin Zhao
- Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
| | - Xu Qian
- Department of Nutrition and Food Hygiene, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital and Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, 21009, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
| | - Xin Ge
- Department of Nutrition and Food Hygiene, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
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8
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Mauliasari IR, Lee HJ, Koo SY, Hitayezu E, Kieu ANT, Lee SM, Cha KH. Benzo(a)pyrene and Gut Microbiome Crosstalk: Health Risk Implications. TOXICS 2024; 12:938. [PMID: 39771153 PMCID: PMC11840287 DOI: 10.3390/toxics12120938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 12/13/2024] [Accepted: 12/17/2024] [Indexed: 02/23/2025]
Abstract
This review delves into the impact of benzo(a)pyrene (B(a)P), which is a toxic and pervasive polycyclic aromatic hydrocarbon (PAH) and known carcinogen, on the human health risk from a gut microbiome perspective. We retrieved the relevant articles on each PAH and summarized the reporting to date, with a particular focus on benzo(a)pyrene, which has been reported to have a high risk of gut microbiome-related harm. B(a)P exposure can compromise the homeostasis of the gut microbiota, leading to dysbiosis, a state of microbial imbalance. The consequences of B(a)P-induced gut dysbiosis can be far-reaching, potentially contributing to inflammation, metabolic disorders, and an increased risk of various diseases. Additionally, due to the strong coupling between B(a)P and microparticles, the toxicity of B(a)P may be further compounded by its reaction with strong gut disruptors such as micro-/nanoplastics, which have recently become a serious environmental concern. This review summarizes current research on the impact of B(a)P on the gut microbiome, highlighting the intricate relationship between environmental exposure, gut health, and human disease. Further research is necessary to elucidate the underlying mechanisms and develop effective strategies to mitigate the adverse health effects of B(a)P exposure.
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Affiliation(s)
- Intan Rizki Mauliasari
- Center for Natural Product Systems Biology, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea; (I.R.M.); (H.J.L.); (S.Y.K.); (E.H.); (A.N.T.K.)
- Department of Aquatic Life Medicine, College of Life Sciences, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea;
| | - Hee Ju Lee
- Center for Natural Product Systems Biology, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea; (I.R.M.); (H.J.L.); (S.Y.K.); (E.H.); (A.N.T.K.)
| | - Song Yi Koo
- Center for Natural Product Systems Biology, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea; (I.R.M.); (H.J.L.); (S.Y.K.); (E.H.); (A.N.T.K.)
| | - Emmanuel Hitayezu
- Center for Natural Product Systems Biology, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea; (I.R.M.); (H.J.L.); (S.Y.K.); (E.H.); (A.N.T.K.)
- Department of Food Science, College of Life Sciences, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea
| | - Anh Nguyen Thi Kieu
- Center for Natural Product Systems Biology, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea; (I.R.M.); (H.J.L.); (S.Y.K.); (E.H.); (A.N.T.K.)
- Natural Products Applied Science, KIST School, University of Science and Technology, Gangneung 25451, Republic of Korea
| | - Sang-Min Lee
- Department of Aquatic Life Medicine, College of Life Sciences, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea;
| | - Kwang Hyun Cha
- Center for Natural Product Systems Biology, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea; (I.R.M.); (H.J.L.); (S.Y.K.); (E.H.); (A.N.T.K.)
- Natural Products Applied Science, KIST School, University of Science and Technology, Gangneung 25451, Republic of Korea
- Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, 20, Ilsan-ro, Wonju 26493, Republic of Korea
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Krisanits BA, Kaur B, Fahey JW, Turner DP. The Anti-AGEing and RAGEing Potential of Isothiocyanates. Molecules 2024; 29:5986. [PMID: 39770075 PMCID: PMC11677037 DOI: 10.3390/molecules29245986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 12/13/2024] [Accepted: 12/15/2024] [Indexed: 01/03/2025] Open
Abstract
Isothiocyanates (ITCs), found in edible plants such as cruciferous vegetables, are a group of reactive organo-sulfur phytochemicals produced by the hydrolysis of precursors known as glucosinolates. ITCs have been studied extensively both in vivo and in vitro to define their therapeutic potential for the treatment of chronic health conditions. Therapeutically, they have shown an intrinsic ability to inhibit oxidative and inflammatory phenotypes to support enhanced health. This review summarizes the current evidence supporting the observation that the antioxidant and anti-inflammatory activities of ITCs temper the pathogenic effects of a group of reactive metabolites called advanced glycation end products (AGEs). AGE exposure has significantly increased across the lifespan due to health risk factors that include dietary intake, a sedentary lifestyle, and comorbid conditions. By contributing to a chronic cycle of inflammatory stress through the aberrant activation of the transmembrane receptor for AGE (RAGE), increased AGE bioavailability is associated with chronic disease onset, progression, and severity. This review debates the potential molecular mechanisms by which ITCs may inhibit AGE bioavailability to reduce RAGE-mediated pro-oxidant and pro-inflammatory phenotypes. Bringing to light the molecular impact that ITCs may have on AGE biogenesis may stimulate novel intervention strategies for reversing or preventing the impact of lifestyle factors on chronic disease risk.
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Affiliation(s)
- Bradley A. Krisanits
- Department of Surgery, School of Medicine, Virginia Commonwealth University, Richmond, VA 23284, USA; (B.A.K.); (B.K.)
- Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23284, USA
| | - Bhoomika Kaur
- Department of Surgery, School of Medicine, Virginia Commonwealth University, Richmond, VA 23284, USA; (B.A.K.); (B.K.)
- Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23284, USA
| | - Jed W. Fahey
- Departments of Medicine, Pharmacology & Molecular Sciences, Psychiatry & Behavioral Sciences, and iMIND Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;
- Institute of Medicine, University of Maine, Orono, ME 04469, USA
| | - David P. Turner
- Department of Surgery, School of Medicine, Virginia Commonwealth University, Richmond, VA 23284, USA; (B.A.K.); (B.K.)
- Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23284, USA
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10
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Properzi S, Stracci F, Rosi M, Lupi C, Villarini A, Gili A. Can a diet rich in Brassicaceae help control Helicobacter pylori infection? A systematic review. Front Med (Lausanne) 2024; 11:1454902. [PMID: 39741515 PMCID: PMC11685009 DOI: 10.3389/fmed.2024.1454902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 11/11/2024] [Indexed: 01/03/2025] Open
Abstract
Introduction Helicobacter pylori (Hp) infection is highly prevalent globally and poses a significant public health challenge due to its link with chronic gastritis, peptic ulcers, and gastric malignancies. Hp's persistence within the gastric environment, particularly in case of infection with virulent strains, triggers chronic inflammatory responses and mucosal damage. Antibiotic therapy is the primary approach for Hp eradication, but antibiotic resistance and adverse effects hinder treatment efficacy. Emerging evidence suggests that Brassicaceae-derived metabolites could serve as adjunctive therapy for Hp infection, offering potential antimicrobial and anti-inflammatory benefits. Methods A systematic literature review was conducted following PRISMA guidelines to assess the impact of Brassicaceae-rich diets on Hp infection control. Searches were performed in MEDLINE PubMed, Web of Science, and the Cochrane Library until 18 October 2023, without language or date restrictions. Eligible studies meeting PICOS criteria were included, encompassing populations infected with Hp or Hp-infected human cell cultures, interventions involving Brassicaceae consumption or its bioactive molecules, and outcomes related to Hp infection control, antibiotic therapy interactions, reduction of antibiotic side effects, and inflammation mitigation. Animal studies, cell line experiments, reviews unrelated to the research objectives, and studies on Hp-related gastric cancer were excluded. Results Available evidence indicates that Brassicaceae consumption exhibits the potential to reduce Hp colonization but achieving complete eradication of the pathogen remains challenging. Conflicting results regarding the efficacy of broccoli in Hp treatment emerge, with certain investigations suggesting limited effectiveness. Other studies point to a potential for heightened eradication rates when combined with standard triple therapy. Furthermore, promising outcomes are observed with broccoli extract supplements, indicating their role in mitigating Hp-induced gastric mucosal damage. In fact, it is noteworthy that sulforaphane and its derivatives manifest notable reductions in pro-inflammatory markers, indicative of their anti-inflammatory properties. Adverse events associated with antibiotic therapy seem unaffected by sulforaphane derivatives or probiotics. However, individual responses to these treatments vary, underscoring the unpredictability of their efficacy in ameliorating antibiotic therapy-related side effects. Conclusion Our systematic review highlights the potential of Brassicaceae-rich diets as adjunctive therapy for Hp infection, offering synergistic interactions with antibiotics and possibly mitigating antibiotic side effects and inflammation. Further research, particularly well-designed randomized trials, is warranted to elucidate the therapeutic efficacy and optimal utilization of Brassicaceae-derived metabolites in managing human Hp-related diseases.
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Affiliation(s)
- Sara Properzi
- Department of Medicine and Surgery, University of Perugia, Perugia, Umbria, Italy
| | - Fabrizio Stracci
- Department of Medicine and Surgery, University of Perugia, Perugia, Umbria, Italy
| | - Margherita Rosi
- Department of Medicine and Surgery, University of Perugia, Perugia, Umbria, Italy
| | - Chiara Lupi
- Department of Medicine and Surgery, University of Perugia, Perugia, Umbria, Italy
| | - Anna Villarini
- Department of Medicine and Surgery, University of Perugia, Perugia, Umbria, Italy
| | - Alessio Gili
- Department of Life Sciences, Health and Health Professions, Link Campus University, Rome, Italy
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11
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Ajuwon OR, Nsole-Biteghe FA, Ndong JD, Davids LM, Ajiboye BO, Brai B, Bamisaye FA, Falode JA, Odoh IM, Adegbite KI, Adegoke BO, Ntwasa M, Lebelo SL, Ayeleso AO. Nrf2-Mediated Antioxidant Response and Drug Efflux Transporters Upregulation as Possible Mechanisms of Resistance in Photodynamic Therapy of Cancers. Onco Targets Ther 2024; 17:605-627. [PMID: 39131905 PMCID: PMC11313505 DOI: 10.2147/ott.s457749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 05/08/2024] [Indexed: 08/13/2024] Open
Abstract
Photodynamic therapy (PDT) is a groundbreaking approach involving the induction of cytotoxic reactive oxygen species (ROS) within tumors through visible light activation of photosensitizers (PS) in the presence of molecular oxygen. This innovative therapy has demonstrated success in treating various cancers. While PDT proves highly effective in most solid tumors, there are indications that certain cancers exhibit resistance, and some initially responsive cancers may develop intrinsic or acquired resistance to PDT. The molecular mechanisms underlying this resistance are not fully understood. Recent evidence suggests that, akin to other traditional cancer treatments, the activation of survival pathways, such as the KEAP1/Nrf2 signaling pathway, is emerging as an important mechanism of post-PDT resistance in many cancers. This article explores the dual role of Nrf2, highlighting evidence linking aberrant Nrf2 expression to treatment resistance across a range of cancers. Additionally, it delves into the specific role of Nrf2 in the context of photodynamic therapy for cancers, emphasizing evidence that suggests Nrf2-mediated upregulation of antioxidant responses and induction of drug efflux transporters are potential mechanisms of resistance to PDT in diverse cancer types. Therefore, understanding the specific role(s) of Nrf2 in PDT resistance may pave the way for the development of more effective cancer treatments using PDT.
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Affiliation(s)
| | | | | | | | | | - Bartholomew Brai
- Department of Biochemistry, Federal University, Oye-Ekiti, Ekiti State, Nigeria
| | | | - John Adeolu Falode
- Department of Biochemistry, Federal University, Oye-Ekiti, Ekiti State, Nigeria
| | - Ikenna Maximillian Odoh
- Department of Biochemistry, Federal University, Oye-Ekiti, Ekiti State, Nigeria
- Medical Center, Federal University, Oye-Ekiti, Ekiti-State, Nigeria
| | - Kabirat Iyabode Adegbite
- Department of Environmental Health Science, College of Basic Medical and Health Sciences, Fountain University, Osogbo, Osun State, Nigeria
| | | | - Monde Ntwasa
- Department of Life and Consumer Sciences, University of South Africa, Florida Park 1709, Roodeport, South Africa
| | - Sogolo Lucky Lebelo
- Department of Life and Consumer Sciences, University of South Africa, Florida Park 1709, Roodeport, South Africa
| | - Ademola Olabode Ayeleso
- Department of Life and Consumer Sciences, University of South Africa, Florida Park 1709, Roodeport, South Africa
- Biochemistry Programme, Bowen University, Iwo, Osun State, Nigeria
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12
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Zhang Y, Zhao X, Liu Y, Yang X. Sulforaphane and ophthalmic diseases. Food Sci Nutr 2024; 12:5296-5311. [PMID: 39139965 PMCID: PMC11317731 DOI: 10.1002/fsn3.4230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 04/25/2024] [Accepted: 05/02/2024] [Indexed: 08/15/2024] Open
Abstract
Sulforaphane (SFN) is an organosulfur compound categorized as an isothiocyanate (ITC), primarily extracted from cruciferous vegetables like broccoli and cabbage. The molecular formula of sulforaphane (SFN) is C6H11NOS2. SFN is generated by the hydrolysis of glucoraphanin (GRP) through the enzyme myrosinase, showing notable properties including anti-diabetic, anti-inflammatory, antimicrobial, anti-angiogenic, and anticancer attributes. Ongoing clinical trials are investigating its potential in diseases such as cancer, neurodegenerative diseases, diabetes-related complications, chronic kidney disease, cardiovascular disease, and liver diseases. Several animal carcinogenesis models and cell culture models have shown it to be a very effective chemopreventive agent, and the protective effects of SFN in ophthalmic diseases have been linked to multiple mechanisms. In murine models of diabetic retinopathy and age-related macular degeneration, SFN delays retinal photoreceptor cell degeneration through the Nrf2 antioxidative pathway, NF-κB pathway, AMPK pathway, and Txnip/mTOR pathway. In rabbit models of keratoconus and cataract, SFN has been shown to protect corneal and lens epithelial cells from oxidative stress injury by activating the Keap1-Nrf2-ARE pathway and the Nrf-2/HO-1 antioxidant pathway. Oral delivery or intraperitoneal injection at varying concentrations are the primary strategies for SFN intake in current preclinical studies. Challenges remain in the application of SFN in eye disorders due to its weak solubility in water and limited bioavailability because of the presence of blood-ocular barrier systems. This review comprehensively outlines recent research on SFN, elucidates its mechanisms of action, and discusses potential therapeutic benefits for eye disorders such as age-related macular degeneration (AMD), diabetic retinopathy (DR), cataracts, and other ophthalmic diseases, while also indicating directions for future clinical research to achieve efficient SFN treatment for ophthalmic diseases.
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Affiliation(s)
- Yichi Zhang
- Department of OphthalmologyThe Fifth Affiliated Hospital of Sun Yat‐sen UniversityZhuhaiChina
| | - Xiaojing Zhao
- Department of OphthalmologyThe Fifth Affiliated Hospital of Sun Yat‐sen UniversityZhuhaiChina
| | - Yang Liu
- Department of OphthalmologyThe Fifth Affiliated Hospital of Sun Yat‐sen UniversityZhuhaiChina
| | - Xiuxia Yang
- Department of OphthalmologyThe Fifth Affiliated Hospital of Sun Yat‐sen UniversityZhuhaiChina
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Zhou ZJ, Dong JY, Qiu Y, Zhang GL, Wei K, He LH, Sun YN, Jiang HZ, Zhang SS, Guo XR, Wang JY, Chen DP. Sulforaphane decreases oxidative stress and inhibits NLRP3 inflammasome activation in a mouse model of ulcerative colitis. Biomed Pharmacother 2024; 175:116706. [PMID: 38713944 DOI: 10.1016/j.biopha.2024.116706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 04/27/2024] [Accepted: 05/02/2024] [Indexed: 05/09/2024] Open
Abstract
Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50 mg·kg-1·d-1, ig) or the positive control sulfasalazine (500 mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1β. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1β, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment.
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Affiliation(s)
- Zi-Juan Zhou
- Comparative Medicine Department of Researching and Teaching, Dalian Medical University, Dalian, Liaoning 116044, China
| | - Jian-Yi Dong
- Comparative Medicine Department of Researching and Teaching, Dalian Medical University, Dalian, Liaoning 116044, China
| | - Yang Qiu
- Dalian Medical University, Dalian, Liaoning 116044, China
| | - Guo-Lin Zhang
- Dalian Medical University, Dalian, Liaoning 116044, China
| | - Kun Wei
- Dalian Medical University, Dalian, Liaoning 116044, China
| | - Li-Heng He
- Dalian Medical University, Dalian, Liaoning 116044, China
| | - Yi-Ning Sun
- Dalian Medical University, Dalian, Liaoning 116044, China
| | | | - Shuang-Shuang Zhang
- Comparative Medicine Department of Researching and Teaching, Dalian Medical University, Dalian, Liaoning 116044, China
| | - Xin-Rui Guo
- Comparative Medicine Department of Researching and Teaching, Dalian Medical University, Dalian, Liaoning 116044, China
| | - Jing-Yu Wang
- Comparative Medicine Department of Researching and Teaching, Dalian Medical University, Dalian, Liaoning 116044, China.
| | - Da-Peng Chen
- Comparative Medicine Department of Researching and Teaching, Dalian Medical University, Dalian, Liaoning 116044, China.
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14
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Bendary MM, Ali MAM, Abdel Halim AS, Boufahja F, Chaudhary AA, Elkelish A, Soliman RHM, Hegazy WAH. Investigating Sulforaphane's anti-virulence and anti-quorum sensing properties against Pseudomonas aeruginosa. Front Pharmacol 2024; 15:1406653. [PMID: 38835668 PMCID: PMC11148281 DOI: 10.3389/fphar.2024.1406653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 04/29/2024] [Indexed: 06/06/2024] Open
Abstract
Background P. aeruginosa, a significant bacterium, can cause severe illness and resistance to antibiotics. Quorum sensing (QS) systems regulate virulence factors production. Targeting QS could reduce bacteria pathogenicity and prevent antibiotic resistance. Cruciferous vegetables contain sulforaphane, known for its anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. Aim We aimed to examine the inhibitory influences of sulforaphane, at a sub-inhibitory concentration (¼ minimum inhibitory concentration, MIC), on virulence and QS in P. aeruginosa. Materials and methods The sulforaphane's anti-virulence actions at sub-inhibitory concentrations were explored in vitro and in vivo. A sub-MIC concentration of sulforaphane was combined with anti-pseudomonal drugs, and the results of this combination were assessed. The virtual affinity of sulforaphane for the receptors of QS was studied, and its effect on the expression of QS genes was quantified. Results Sulforaphane significantly decreased the biofilm formation, motility, ability to withstand oxidative stress, and the synthesis of virulence extracellular enzymes such as proteases, hemolysins, and elastase, as well as other virulence factors like pyocyanin. In addition, sulforaphane lessened the severity of P. aeruginosa infection in mice. Sulforaphane reduced the antipseudomonal antibiotics' MICs when used together, resulting in synergistic effects. The observed anti-virulence impacts were attributed to the ability of sulforaphane to inhibit QS via suppressing the QS genes' expression. Conclusion Sulforaphane shows promise as a potent anti-virulence and anti-QS agent that can be used alongside conventional antimicrobials to manage severe infections effectively. Furthermore, this study paves the way for further investigation of sulforaphane and similar structures as pharmacophores for anti-QS candidates.
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Affiliation(s)
- Mahmoud M Bendary
- Department of Microbiology and Immunology, Faculty of Pharmacy, Port Said University, Port Said, Egypt
| | - Mohamed A M Ali
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Alyaa S Abdel Halim
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Fehmi Boufahja
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
| | - Anis Ahmad Chaudhary
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
| | - Amr Elkelish
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
- Department of Botany and Microbiology, Faculty of Science, Suez Canal University, Ismailia, Egypt
| | - Rania H M Soliman
- Department of Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Wael A H Hegazy
- Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
- Pharmacy Program, Department of Pharmaceutical Sciences, Oman College of Health Sciences, Muscat, Oman
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15
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Zhang J, Liu K, Tang X, Wang XJ. Dysfunction of Nrf2-regulated cellular defence system and JNK activation induced by high dose of fly Ash particles are associated with pulmonary injury in mouse lungs. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 275:116239. [PMID: 38518612 DOI: 10.1016/j.ecoenv.2024.116239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 03/15/2024] [Accepted: 03/17/2024] [Indexed: 03/24/2024]
Abstract
The mechanisms of the exposure to fine particulate matter (PM) as a risk factor for pulmonary injury are not fully understood. The transcription factor, NF-E2-related factor 2 (Nrf2), plays a key role in protection lung against PM insult and cancer chemoprevention. In this study, F3-S fly ash particles from a municipal waste incinerator were evaluated as a PM model. We found that F3-S triggered hierarchical oxidative stress responses involving the prolonged activation of the cytoprotective Nrf2 transcriptional program via Keap1 Cys151 modification, and c-Jun NH2-terminal kinase (JNK) phosphorylation at higher doses. In mouse lungs exposed to fly ash particles at a low dose (10-20 mg/kg), Nrf2 signalling was upregulated, while in those exposed to a high fly ash particle dose (40 mg/kg), there was significant activation of JNK, and this correlated with Nrf2 phosphorylation and the downregulation of antioxidant response element (ARE)-driven genes. The JNK inhibitor, SP600125, reversed Nrf2 phosphorylation, and downregulation of detoxifying enzymes. Silencing JNK expression in mouse lungs using adenoviral shRNA inhibited JNK activation and Nrf2 phosphorylation, promoted ARE-driven gene expression, and reduced pulmonary injury. Furthermore, we found that the 452-515 amino acid region within the Neh1 domain of Nrf2 was required for its interaction with P-JNK. We demonstrated that Nrf2 was an important P-JNK target in fly ash-induced pulmonary toxicity. JNK phosphorylated Nrf2, leading to a dysfunction of the Nrf2-mediated defence system.
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Affiliation(s)
- Jingwen Zhang
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention of the Ministry of Education), and Department of Pharmacology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, PR China
| | - Kaihua Liu
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention of the Ministry of Education), and Department of Pharmacology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, PR China
| | - Xiuwen Tang
- Department of Biochemistry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, PR China.
| | - Xiu Jun Wang
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention of the Ministry of Education), and Department of Pharmacology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, PR China.
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Huang Q, Liu J, Peng C, Han X, Tan Z. Hesperidin ameliorates H 2O 2-induced bovine mammary epithelial cell oxidative stress via the Nrf2 signaling pathway. J Anim Sci Biotechnol 2024; 15:57. [PMID: 38589950 PMCID: PMC11003082 DOI: 10.1186/s40104-024-01012-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 02/07/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Hesperidin is a citrus flavonoid with anti-inflammatory and antioxidant potential. However, its protective effects on bovine mammary epithelial cells (bMECs) exposed to oxidative stress have not been elucidated. RESULTS In this study, we investigated the effects of hesperidin on H2O2-induced oxidative stress in bMECs and the underlying molecular mechanism. We found that hesperidin attenuated H2O2-induced cell damage by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, increasing catalase (CAT) activity, and improving cell proliferation and mitochondrial membrane potential. Moreover, hesperidin activated the Keap1/Nrf2/ARE signaling pathway by inducing the nuclear translocation of Nrf2 and the expression of its downstream genes NQO1 and HO-1, which are antioxidant enzymes involved in ROS scavenging and cellular redox balance. The protective effects of hesperidin were blocked by the Nrf2 inhibitor ML385, indicating that they were Nrf2 dependent. CONCLUSIONS Our results suggest that hesperidin could protect bMECs from oxidative stress injury by activating the Nrf2 signaling pathway, suggesting that hesperidin as a natural antioxidant has positive potential as a feed additive or plant drug to promote the health benefits of bovine mammary.
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Affiliation(s)
- Qi Huang
- CAS Key Laboratory for Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, Hunan, China
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Jiashuo Liu
- CAS Key Laboratory for Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, Hunan, China
| | - Can Peng
- CAS Key Laboratory for Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, Hunan, China
| | - Xuefeng Han
- CAS Key Laboratory for Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, Hunan, China.
| | - Zhiliang Tan
- CAS Key Laboratory for Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, Hunan, China
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Balakina AA, Amozova VI, Prikhodchenko TR, Stupina TS, Mishchenko DV. Effect of Pyridoxine Derivative B6NO on Transcription Factor Nrf2 Activity and Cytotoxic Properties of Doxorubicin In Vitro. Bull Exp Biol Med 2024; 176:687-696. [PMID: 38733479 DOI: 10.1007/s10517-024-06091-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Indexed: 05/13/2024]
Abstract
The effect of a new pyridoxine derivative B6NO on doxorubicin cytotoxicity and Nrf2-dependent cellular processes in vitro was studied. Antioxidant B6NO enhances the cytotoxic effect of doxorubicin on tumor cells, which is associated with G2/M cell division arrest and an increase in activity of proapoptotic enzyme caspase-3. The antioxidant promotes intracellular accumulation and nuclear translocation of Nrf2 transcription factor in non-tumor and tumor cells. In non-tumor cells, B6NO increases the expression of antioxidant system proteins and reduces ROS generation in the presence of doxorubicin. In tumor cells, no activation of Nrf2-dependent processes occurs under the action of the antioxidant. Our findings demonstrate the prospect of further studies of pyridoxine derivatives as antioxidants to reduce adverse reactions during chemotherapy.
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Affiliation(s)
- A A Balakina
- Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Chernogolovka, Moscow Region, Russia.
| | - V I Amozova
- Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Chernogolovka, Moscow Region, Russia
| | - T R Prikhodchenko
- Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Chernogolovka, Moscow Region, Russia
| | - T S Stupina
- Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Chernogolovka, Moscow Region, Russia
| | - D V Mishchenko
- Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Chernogolovka, Moscow Region, Russia
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18
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Men X, Han X, Oh G, Im JH, Lim JS, Cho GH, Choi SI, Lee OH. Plant sources, extraction techniques, analytical methods, bioactivity, and bioavailability of sulforaphane: a review. Food Sci Biotechnol 2024; 33:539-556. [PMID: 38274178 PMCID: PMC10805900 DOI: 10.1007/s10068-023-01434-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 09/06/2023] [Accepted: 09/10/2023] [Indexed: 01/27/2024] Open
Abstract
Sulforaphane (SFN) is an isothiocyanate commonly found in cruciferous vegetables. It is formed via the enzymatic hydrolysis of glucoraphanin by myrosinase. SFN exerts various biological effects, including anti-cancer, anti-oxidation, anti-obesity, and anti-inflammatory effects, and is widely used in functional foods and clinical medicine. However, the structure of SFN is unstable and easily degradable, and its production is easily affected by temperature, pH, and enzyme activity, which limit its application. Hence, several studies are investigating its physicochemical properties, stability, and biological activity to identify methods to increase its content. This article provides a comprehensive review of the plant sources, extraction and analysis techniques, in vitro and in vivo biological activities, and bioavailability of SFN. This article highlights the importance and provides a reference for the research and application of SFN in the future.
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Affiliation(s)
- Xiao Men
- Department of Food Biotechnology and Environmental Science, Kangwon National University, Chuncheon, 24341 Republic of Korea
| | - Xionggao Han
- Department of Food Biotechnology and Environmental Science, Kangwon National University, Chuncheon, 24341 Republic of Korea
| | - Geon Oh
- Department of Food Biotechnology and Environmental Science, Kangwon National University, Chuncheon, 24341 Republic of Korea
| | - Ji-Hyun Im
- Department of Food Biotechnology and Environmental Science, Kangwon National University, Chuncheon, 24341 Republic of Korea
| | - June seok Lim
- Department of Food Biotechnology and Environmental Science, Kangwon National University, Chuncheon, 24341 Republic of Korea
| | - Geun hee Cho
- Department of Food Biotechnology and Environmental Science, Kangwon National University, Chuncheon, 24341 Republic of Korea
| | - Sun-Il Choi
- Department of Food Biotechnology and Environmental Science, Kangwon National University, Chuncheon, 24341 Republic of Korea
| | - Ok-Hwan Lee
- Department of Food Biotechnology and Environmental Science, Kangwon National University, Chuncheon, 24341 Republic of Korea
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19
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Sheoran S, Arora S, Velingkar A, Pawar SC, Vuree S. Empowering treatment strategies for pancreatic cancer by employing lipid nanoparticle-driven drug delivery. RECENT ADVANCES IN NANOCARRIERS FOR PANCREATIC CANCER THERAPY 2024:239-266. [DOI: 10.1016/b978-0-443-19142-8.00016-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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20
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Garcia-Ibañez P, Silvan JM, Moreno DA, Carvajal M, Martinez-Rodriguez AJ. Influence of Source Materials, Concentration, Gastric Digestion, and Encapsulation on the Bioactive Response of Brassicaceae-Derived Samples against Helicobacter pylori. Microorganisms 2023; 12:77. [PMID: 38257906 PMCID: PMC10820487 DOI: 10.3390/microorganisms12010077] [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: 12/01/2023] [Revised: 12/22/2023] [Accepted: 12/27/2023] [Indexed: 01/24/2024] Open
Abstract
Isothiocyanates may have antibacterial activity against Helicobacter pylori, but there are different variables related to Brassicaceae-derived samples that could affect their efficacy. This work studied the influence of source variety, concentration, gastric digestion, and encapsulation of samples on their bioactive response against Helicobacter pylori. The antibacterial activity of raw sprouts (red cabbage and red radish) showed the highest antibacterial effect, which was consistent with a higher amount of isothiocyanates. It decreased with gastric digestion, regardless of sample encapsulation. By contrast, adult red radish leaves became antibacterial after gastric digestion. Antioxidant activity on H. pylori-infected gastric cells was similar in all samples and followed an equivalent pattern with the changes in isothiocyanates. Raw samples decreased intracellular reactive oxygen species production, but they lost this capacity after gastric digestion, regardless whether the compounds were free or encapsulated. Red cabbage sprouts, red radish sprouts, and red radish roots produced a decrease in nitric oxide production. It was consistent with a modulation of the inflammatory response and was associated to isothiocyanates concentration. Encapsulated sprout samples retained part of their anti-inflammatory activity after gastric digestion. Adult raw red radish leaves were not active, but after digestion, they became anti-inflammatory. The results obtained in this study have shown that several variables could have a significant impact on the bioactive properties of Brassicaceae-derived samples against H. pylori, providing a starting point for the design and standardization of samples with specific bioactivities (antibacterial, antioxidant, and anti-inflammatory) potentially useful for the treatment of H. pylori infection.
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Affiliation(s)
- Paula Garcia-Ibañez
- Grupo de Aquaporinas, Departamento de Nutrición Vegetal, Centro de Edafología y Biología Aplicada del Segura (CEBAS), Consejo Superior de Investigaciones Cientificas (CSIC), Campus Universitario de Espinardo, Edificio 25, 30100 Murcia, Spain; (P.G.-I.); (M.C.)
| | - Jose Manuel Silvan
- Grupo de Microbiología y Biocatálisis de Alimentos (MICROBIO), Departamento de Biotecnología y Microbiología, Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM (Consejo Superior de Investigaciones Cientificas-Universidad Autonoma de Madrid), C/Nicolas Cabrera 9, Universidad Autónoma de Madrid, 28049 Madrid, Spain
| | - Diego A. Moreno
- Phytochemistry and Healthy Food Laboratory, Departamento de Ciencia y Tecnología de Alimentos, Centro de Edafología y Biología Aplicada del Segura (CEBAS), Consejo Superior de Investigaciones Cientificas (CSIC), Campus Universitario de Espinardo, Edificio 25, 30100 Murcia, Spain;
| | - Micaela Carvajal
- Grupo de Aquaporinas, Departamento de Nutrición Vegetal, Centro de Edafología y Biología Aplicada del Segura (CEBAS), Consejo Superior de Investigaciones Cientificas (CSIC), Campus Universitario de Espinardo, Edificio 25, 30100 Murcia, Spain; (P.G.-I.); (M.C.)
| | - Adolfo J. Martinez-Rodriguez
- Grupo de Microbiología y Biocatálisis de Alimentos (MICROBIO), Departamento de Biotecnología y Microbiología, Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM (Consejo Superior de Investigaciones Cientificas-Universidad Autonoma de Madrid), C/Nicolas Cabrera 9, Universidad Autónoma de Madrid, 28049 Madrid, Spain
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21
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Holcomb L, Holman JM, Hurd M, Lavoie B, Colucci L, Hunt B, Hunt T, Kinney M, Pathak J, Mawe GM, Moses PL, Perry E, Stratigakis A, Zhang T, Chen G, Ishaq SL, Li Y. Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease. mSystems 2023; 8:e0068823. [PMID: 37942948 PMCID: PMC10734470 DOI: 10.1128/msystems.00688-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 10/02/2023] [Indexed: 11/10/2023] Open
Abstract
IMPORTANCE To our knowledge, IL-10-KO mice have not previously been used to investigate the interactions of host, microbiota, and broccoli, broccoli sprouts, or broccoli bioactives in resolving symptoms of CD. We showed that a diet containing 10% raw broccoli sprouts increased the plasma concentration of the anti-inflammatory compound sulforaphane and protected mice to varying degrees against disease symptoms, including weight loss or stagnation, fecal blood, and diarrhea. Younger mice responded more strongly to the diet, further reducing symptoms, as well as increased gut bacterial richness, increased bacterial community similarity to each other, and more location-specific communities than older mice on the diet intervention. Crohn's disease disrupts the lives of patients and requires people to alter dietary and lifestyle habits to manage symptoms. The current medical treatment is expensive with significant side effects, and a dietary intervention represents an affordable, accessible, and simple strategy to reduce the burden of symptoms.
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Affiliation(s)
- Lola Holcomb
- Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA
| | - Johanna M. Holman
- School of Food and Agriculture, University of Maine, Orono, Maine, USA
| | - Molly Hurd
- Larner College of Medicine, University of Vermont, Burlington, Vermont, USA
| | - Brigitte Lavoie
- Larner College of Medicine, University of Vermont, Burlington, Vermont, USA
| | - Louisa Colucci
- Department of Biology, Husson University, Bangor, Maine, USA
| | - Benjamin Hunt
- Department of Biology, University of Maine, Orono, Maine, USA
| | - Timothy Hunt
- Department of Biology, University of Maine, Orono, Maine, USA
| | - Marissa Kinney
- School of Food and Agriculture, University of Maine, Orono, Maine, USA
| | - Jahnavi Pathak
- Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA
| | - Gary M. Mawe
- Larner College of Medicine, University of Vermont, Burlington, Vermont, USA
| | - Peter L. Moses
- Larner College of Medicine, University of Vermont, Burlington, Vermont, USA
- Finch Therapeutics, Somerville, Massachusetts, USA
| | - Emma Perry
- Electron Microscopy Laboratory, University of Maine, Orono, Maine, USA
| | - Allesandra Stratigakis
- School of Pharmacy and Pharmaceutical Sciences, SUNY Binghamton University, Johnson City, New York, USA
| | - Tao Zhang
- School of Pharmacy and Pharmaceutical Sciences, SUNY Binghamton University, Johnson City, New York, USA
| | - Grace Chen
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Suzanne L. Ishaq
- Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA
| | - Yanyan Li
- Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA
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22
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Wang C, Yao M, Zhong H, Meena SS, Shu F, Nie S, Xie M. Natural foods resources and dietary ingredients for the amelioration of Helicobacter pylori infection. Front Med (Lausanne) 2023; 10:1324473. [PMID: 38131043 PMCID: PMC10734694 DOI: 10.3389/fmed.2023.1324473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 11/16/2023] [Indexed: 12/23/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a gastric-persistent pathogen that can cause peptic ulcer disease, gastric cancer, and mucosal-associated lymphoid tissue lymphoma. This pathogen is commonly treated with antibiotic-based triple or quadruple therapy. However, antibiotic therapy could result in the bacterial resistance, imbalance of gut microbiota, and damage to the liver and kidneys, etc. Therefore, there is an urgent need for alternative therapeutic strategies. Interestingly, natural food resources, like vegetables, fruits, spices, and edible herbs, have potent inhibitory effects on H. pylori. In this review, we systematically summarized these foods with supporting evidence from both animal and clinical studies. The results have indicated that natural foods may possess temporary inhibition effect on H. pylori rather than durable eradication, and may help to reduce H. pylori colonization, enhance the effect of antibiotics and modulate the host's immune response.
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Affiliation(s)
- Chengyuan Wang
- State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, Jiangxi, China
| | - Meixiang Yao
- Jiangzhong Dietary Therapy Technology Co. Ltd, Jiujiang, Jiangxi, China
| | - Hongguang Zhong
- Jiangzhong Dietary Therapy Technology Co. Ltd, Jiujiang, Jiangxi, China
| | - Stephene S. Meena
- Jiangzhong Cancer Research, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
| | - Fuxing Shu
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiangsu, China
| | - Shaoping Nie
- State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, Jiangxi, China
| | - Mingyong Xie
- State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, Jiangxi, China
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23
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Ye X, Toyama T, Taguchi K, Arisawa K, Kaneko T, Tsutsumi R, Yamamoto M, Saito Y. Sulforaphane decreases serum selenoprotein P levels through enhancement of lysosomal degradation independent of Nrf2. Commun Biol 2023; 6:1060. [PMID: 37857700 PMCID: PMC10587141 DOI: 10.1038/s42003-023-05449-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 10/11/2023] [Indexed: 10/21/2023] Open
Abstract
Selenoprotein P (SeP) is a major selenoprotein in serum predominantly produced in the liver. Excess SeP impairs insulin secretion from the pancreas and insulin sensitivity in skeletal muscle, thus inhibition of SeP could be a therapeutic strategy for type 2 diabetes. In this study, we examine the effect of sulforaphane (SFN), a phytochemical of broccoli sprouts and an Nrf2 activator, on SeP expression in vitro and in vivo. Treatment of HepG2 cells with SFN decreases inter- and intra-cellular SeP levels. SFN enhances lysosomal acidification and expression of V-ATPase, and inhibition of this process cancels the decrease of SeP by SFN. SFN activates Nrf2 in the cells, while Nrf2 siRNA does not affect the decrease of SeP by SFN or lysosomal acidification. These results indicate that SFN decreases SeP by enhancing lysosomal degradation, independent of Nrf2. Injection of SFN to mice results in induction of cathepsin and a decrease of SeP in serum. The findings from this study are expected to contribute to developing SeP inhibitors in the future, thereby contributing to treating and preventing diseases related to increased SeP.
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Affiliation(s)
- Xinying Ye
- Laboratory of Molecular Biology and Metabolism, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan
| | - Takashi Toyama
- Laboratory of Molecular Biology and Metabolism, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
| | - Keiko Taguchi
- Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
| | - Kotoko Arisawa
- Laboratory of Molecular Biology and Metabolism, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan
| | - Takayuki Kaneko
- Laboratory of Molecular Biology and Metabolism, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan
| | - Ryouhei Tsutsumi
- Laboratory of Molecular Biology and Metabolism, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan
| | - Masayuki Yamamoto
- Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
| | - Yoshiro Saito
- Laboratory of Molecular Biology and Metabolism, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
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24
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Uddin N, Acter T, Rashid MH, Chowdhury AI, Jahan EA. Coping with the COVID-19 pandemic by strengthening immunity as a nonpharmaceutical intervention: A major public health challenge. Health Sci Rep 2023; 6:e1562. [PMID: 37720166 PMCID: PMC10500053 DOI: 10.1002/hsr2.1562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 08/18/2023] [Accepted: 08/22/2023] [Indexed: 09/19/2023] Open
Abstract
Background and Aims The global Coronavirus-2 outbreak has emerged as a significant threat to majority of individuals around the world. The most effective solution for addressing this viral outbreak is through vaccination. Simultaneously, the virus's mutation capabilities pose a potential risk to the effectiveness of both vaccines and, in certain instances, newly developed drugs. Conversely, the human body's immune system exhibits a robust ability to combat viral outbreaks with substantial confidence, as evidenced by the ratio of fatalities to affected individuals worldwide. Hence, an alternative strategy to mitigate this pandemic could involve enhancing the immune system's resilience. Methods The research objective of the review is to acquire a comprehensive understanding of the role of inflammation and immunity in COVID-19. The pertinent literature concerning immune system functions, the impact of inflammation against viruses like SARS-CoV-2, and the connection between nutritional interventions, inflammation, and immunity was systematically explored. Results Enhancing immune function involves mitigating the impact of key factors that negatively influence the immune response. Strengthening the immune system against emerging diseases can be achieved through nonpharmaceutical measures such as maintaining a balanced nutrition, engaging in regular exercise, ensuring adequate sleep, and managing stress. Conclusion This review aims to convey the significance of and provide recommendations for immune-strengthening strategies amidst the ongoing COVID-19 pandemic.
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Affiliation(s)
- Nizam Uddin
- Department of Nutrition and Food Engineering, Faculty of Allied Health ScienceDaffodil International UniversityDhakaBangladesh
| | - Thamina Acter
- Department of Mathematical and Physical SciencesEast West UniversityDhakaBangladesh
| | - Md. Harun‐Ar Rashid
- Department of Nutrition and Food Engineering, Faculty of Allied Health ScienceDaffodil International UniversityDhakaBangladesh
| | - Akibul Islam Chowdhury
- Department of Nutrition and Food Engineering, Faculty of Allied Health ScienceDaffodil International UniversityDhakaBangladesh
| | - Effat Ara Jahan
- Department of Nutrition and Food Engineering, Faculty of Allied Health ScienceDaffodil International UniversityDhakaBangladesh
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25
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Houghton CA. The Rationale for Sulforaphane Favourably Influencing Gut Homeostasis and Gut-Organ Dysfunction: A Clinician's Hypothesis. Int J Mol Sci 2023; 24:13448. [PMID: 37686253 PMCID: PMC10487861 DOI: 10.3390/ijms241713448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 08/17/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023] Open
Abstract
Given the increasing scientific, clinical and consumer interest in highly prevalent functional gastrointestinal disorders, appropriate therapeutic strategies are needed to address the many aspects of digestive dysfunction. Accumulating evidence for the crucifer-derived bioactive molecule sulforaphane in upstream cellular defence mechanisms highlights its potential as a therapeutic candidate in targeting functional gastrointestinal conditions, as well as systemic disorders. This article catalogues the evolution of and rationale for a hypothesis that multifunctional sulforaphane can be utilised as the initial step in restoring the ecology of the gut ecosystem; it can do this primarily by targeting the functions of intestinal epithelial cells. A growing body of work has identified the colonocyte as the driver of dysbiosis, such that targeting gut epithelial function could provide an alternative to targeting the microbes themselves for the remediation of microbial dysbiosis. The hypothesis discussed herein has evolved over several years and is supported by case studies showing the application of sulforaphane in gastrointestinal disorders, related food intolerance, and several systemic conditions. To the best of our knowledge, this is the first time the effects of sulforaphane have been reported in a clinical environment, with several of its key properties within the gut ecosystem appearing to be related to its nutrigenomic effects on gene expression.
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Affiliation(s)
- Christine A. Houghton
- Institute for Nutrigenomic Medicine, Cleveland, QLD 4163, Australia; ; Tel.: +617-3488-0385
- Cell-Logic, 132-140 Ross Court, Cleveland, QLD 4163, Australia
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26
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Mukherjee AG, Gopalakrishnan AV. The mechanistic insights of the antioxidant Keap1-Nrf2 pathway in oncogenesis: a deadly scenario. Med Oncol 2023; 40:248. [PMID: 37480500 DOI: 10.1007/s12032-023-02124-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 07/06/2023] [Indexed: 07/24/2023]
Abstract
The Nuclear factor erythroid 2-related factor 2 (Nrf2) protein has garnered significant interest due to its crucial function in safeguarding cells and tissues. The Nrf2 protein is crucial in preserving tissue integrity by safeguarding cells against metabolic, xenobiotic and oxidative stress. Due to its various functions, Nrf2 is a potential pharmacological target for reducing the incidence of diseases such as cancer. However, mutations in Keap1-Nrf2 are not consistently favored in all types of cancer. Instead, they seem to interact with specific driver mutations of tumors and their respective tissue origins. The Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 pathway mutations are a powerful cancer adaptation that utilizes inherent cytoprotective pathways, encompassing nutrient metabolism and ROS regulation. The augmentation of Nrf2 activity elicits significant alterations in the characteristics of neoplastic cells, such as resistance to radiotherapy and chemotherapy, safeguarding against apoptosis, heightened invasiveness, hindered senescence, impaired autophagy and increased angiogenesis. The altered activity of Nrf2 can arise from diverse genetic and epigenetic modifications that instantly impact Nrf2 regulation. The present study aims to showcase the correlation between the Keap1-Nrf2 pathway and the progression of cancers, emphasizing genetic mutations, metabolic processes, immune regulation, and potential therapeutic strategies. This article delves into the intricacies of Nrf2 pathway anomalies in cancer, the potential ramifications of uncontrolled Nrf2 activity, and therapeutic interventions to modulate the Keap1-Nrf2 pathway.
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Affiliation(s)
- Anirban Goutam Mukherjee
- Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India
| | - Abilash Valsala Gopalakrishnan
- Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India.
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27
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Mohammadi M, Attar A, Mohammadbeigi M, Peymani A, Bolori S, Fardsanei F. The possible role of Helicobacter pylori in liver diseases. Arch Microbiol 2023; 205:281. [PMID: 37430019 DOI: 10.1007/s00203-023-03602-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 05/15/2023] [Accepted: 05/29/2023] [Indexed: 07/12/2023]
Abstract
According to previous studies, Helicobacter pylori infection is associated with liver disease. In order to better understand the risk of acquiring various liver diseases, we reviewed current knowledge on the impact of H. pylori on the onset, intensification, and progression of various liver diseases caused by the infection of H. pylori. It has been estimated that between 50 and 90% of people worldwide have been infected with H. pylori. The bacterium is mostly responsible for inflamed gastric mucosa, ulcers, and cancers associated with the gastric mucosa. Through the active antioxidant system in H. pylori, the bacteria can neutralize free radicals by synthesizing VacA, a toxin that causes cell damage and apoptosis. Furthermore, there is a possibility that CagA genes may play a role in cancer development. People who have been infected with H. pylori are likely to develop lesions in the skin, the circulation system, and the pancreas. Moreover, transferring blood from the stomach may allow H. pylori to colonize the liver. The bacterium worsened liver function during autoimmune inflammation, toxic injury, chronic HCV infection, chronic HBV infection, and liver cirrhosis. Increasing portal pressure, hyperammonemia, and esophageal varices may be associated with H pylori infection. As a result, it is crucial to diagnose and treat this infection in patients with H. pylori.
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Affiliation(s)
- Mahnaz Mohammadi
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Adeleh Attar
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Maryam Mohammadbeigi
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Amir Peymani
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Shahin Bolori
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Fatemeh Fardsanei
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
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28
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Holcomb L, Holman JM, Hurd M, Lavoie B, Colucci L, Hunt B, Hunt T, Kinney M, Pathak J, Mawe GM, Moses PL, Perry E, Stratigakis A, Zhang T, Chen G, Ishaq SL, Li Y. Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.01.27.525953. [PMID: 36747766 PMCID: PMC9900910 DOI: 10.1101/2023.01.27.525953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Crohn's Disease (CD) is a presentation of Inflammatory Bowel Disease (IBD) that manifests in childhood and adolescence, and involves chronic and severe enterocolitis, immune and gut microbiome dysregulation, and other complications. Diet and gut-microbiota-produced metabolites are sources of anti-inflammatories which could ameliorate symptoms. However, questions remain on how IBD influences biogeographic patterns of microbial location and function in the gut, how early life transitional gut communities are affected by IBD and diet interventions, and how disruption to biogeography alters disease mediation by diet components or microbial metabolites. Many studies on diet and IBD use a chemically induced ulcerative colitis model, despite the availability of an immune-modulated CD model. Interleukin-10-knockout (IL-10-KO) mice on a C57BL/6 background, beginning at age 4 or 7 weeks, were fed a control diet or one containing 10% (w/w) raw broccoli sprouts, which was high in the sprout-sourced anti-inflammatory sulforaphane. Diets began 7 days prior to, and for 2 weeks after inoculation with Helicobacter hepaticus, which triggers Crohn's-like symptoms in these immune-impaired mice. The broccoli sprout diet increased sulforaphane in plasma; decreased weight stagnation, fecal blood, and diarrhea associated; and increased microbiota richness in the gut, especially in younger mice. Sprout diets resulted in some anatomically specific bacteria in younger mice, and reduced the prevalence and abundance of pathobiont bacteria which trigger inflammation in the IL-10-KO mouse, for example; Escherichia coli and Helicobacter. Overall, the IL-10-KO mouse model is responsive to a raw broccoli sprout diet and represents an opportunity for more diet-host-microbiome research.
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Affiliation(s)
- Lola Holcomb
- Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA 04469
| | - Johanna M. Holman
- School of Food and Agriculture, University of Maine, Orono, Maine, USA 04469
| | - Molly Hurd
- Larner College of Medicine, University of Vermont, Burlington, Vermont, USA 05401
| | - Brigitte Lavoie
- Larner College of Medicine, University of Vermont, Burlington, Vermont, USA 05401
| | - Louisa Colucci
- Department of Biology, Husson University, Bangor, Maine, USA 04401
| | - Benjamin Hunt
- Department of Biology, University of Maine, Orono, Maine, USA 04469
| | - Timothy Hunt
- Department of Biology, University of Maine, Orono, Maine, USA 04469
| | - Marissa Kinney
- School of Food and Agriculture, University of Maine, Orono, Maine, USA 04469
| | - Jahnavi Pathak
- Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA 04469
| | - Gary M. Mawe
- Larner College of Medicine, University of Vermont, Burlington, Vermont, USA 05401
| | - Peter L. Moses
- Larner College of Medicine, University of Vermont, Burlington, Vermont, USA 05401
- Finch Therapeutics, Somerville, Massachusetts, USA 02143
| | - Emma Perry
- Electron Microscopy Laboratory, University of Maine, Orono, Maine, USA 04469
| | - Allesandra Stratigakis
- School of Pharmacy and Pharmaceutical Sciences, SUNY Binghamton University, Johnson City, New York, USA 13790
| | - Tao Zhang
- School of Pharmacy and Pharmaceutical Sciences, SUNY Binghamton University, Johnson City, New York, USA 13790
| | - Grace Chen
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA 48109
| | - Suzanne L. Ishaq
- Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA 04469
| | - Yanyan Li
- Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA 04469
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Abdel-Massih RM, Debs E, Othman L, Attieh J, Cabrerizo FM. Glucosinolates, a natural chemical arsenal: More to tell than the myrosinase story. Front Microbiol 2023; 14:1130208. [PMID: 37089539 PMCID: PMC10114928 DOI: 10.3389/fmicb.2023.1130208] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 03/13/2023] [Indexed: 04/08/2023] Open
Abstract
Glucosinolates are a group of thioglucosides that belong to the class of plant nitrogen-containing natural products. So far, very little biological activity has been associated with intact glucosinolates. The hydrolysis of glucosinolates has, for long, attracted attention because of the potent biological activity of the hydrolysis products. From allelopathic to antiparasitic, antimicrobial and antineoplastic effects, the activity spectrum of the degradation products of typical glucosinolates has been the subject of much research. The present review seeks to address the various means of glucosinolate degradation (thermal, enzymatic, or chemical degradation) and the ensuing products. It also aims to draw a comparative profile of the various antimicrobial effects of these degradation products to provide a further understanding of the biological function of these important compounds.
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Affiliation(s)
| | - Espérance Debs
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, El-Koura, Lebanon
| | - Leen Othman
- Faculty of Medicine and Medical Sciences, University of Balamand, El-Koura, Lebanon
| | - Jihad Attieh
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, El-Koura, Lebanon
| | - Franco M. Cabrerizo
- Instituto Tecnológico de Chascomús, National Scientific and Technical Research Council – National University of General San Martín, Chascomús, Argentina
- Escuela de Bio y Nanotecnologías, National University of General San Martín, Buenos Aires, Argentina
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Zhao Y, Yang D, Liu Y, Han F, Li Z. A highly efficient genetic transformation system for broccoli and subcellular localization. FRONTIERS IN PLANT SCIENCE 2023; 14:1091588. [PMID: 36937998 PMCID: PMC10018207 DOI: 10.3389/fpls.2023.1091588] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 02/14/2023] [Indexed: 06/18/2023]
Abstract
INTRODUCTION Agrobacterium-mediated genetic transformation has been widely used for the identification of functional genes and regulatory and developmental mechanisms in plants. However, there are still some problems of low genetic transformation efficiency and high genotype dependence in cruciferous crops. METHODS In this study, broccoli, a worldwide Brassica crop, was used to investigate the effects of genotype, explant type, concentration of hygromycin B used during seedling selection, overexpression vector type, RNAi and CRISPR/cas9 on the genetic transformation efficiency. At the same time, two vectors, PHG-031350 and PHG-CRa, were used for subcellular localization of the glucoraphanin synthesis-related gene FMOGS-OX5 and clubroot resistance gene by a PEG-Ca2+-mediated transient transformation system for broccoli protoplasts. Finally, the Agrobacterium-mediated genetic transformation system of broccoli was optimized and improved. RESULTS AND DISCUSSION This study showed that hypocotyl explants are more suitable for Agrobacterium-mediated transgene and CRISPR/Cas9 gene editing of broccoli. In contrast to previous studies, we found that 5 mg/L hygromycin B was more advantageous for the selection of resistant broccoli sprouts, and genotype 19B42 reached the highest transformation rate of 26.96%, which is higher than that in Brassica oleracea crops. In addition, the inbred line 19B42 successfully achieved high genetic transformation of overexpression, RNAi and CRISPR/Cas9 vectors; thus, it is powerful recipient material for the genetic transformation of broccoli. Subcellular localization proved that the glucoraphanin metabolism-related gene Bol031350 and clubroot resistance gene CRa were both expressed in the cytoplasm and nucleus, which provided a scientific basis for studying the regulation of glucosinolate metabolism and clubroot resistance in cruciferous crops. Therefore, these findings will provide new insight into the improvement of the genetic transformation and molecular breeding of Brassica oleracea crops.
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Chen B, Liu Y, Xiang C, Zhang D, Liu Z, Liu Y, Chen J. Identification and in vitro enzymatic activity analysis of the AOP2 gene family associated with glucosinolate biosynthesis in Tumorous stem mustard ( Brassica juncea var. tumida). FRONTIERS IN PLANT SCIENCE 2023; 14:1111418. [PMID: 36909383 PMCID: PMC9992552 DOI: 10.3389/fpls.2023.1111418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 02/13/2023] [Indexed: 06/18/2023]
Abstract
The major enzyme encoded by the glucosinolate biosynthetic gene AOP2 is involved in catalyzing the conversion of glucoiberin (GIB) into sinigrin (SIN) in Brassicaceae crops. The AOP2 proteins have previously been identified in several Brassicaceae species, but not in Tumorous stem mustard. As per this research, the five identified members of the AOP2 family from the whole genome of Brassica juncea named BjuAOP2.1-BjuAOP2.5 were found to be evenly distributed on five chromosomes. The subcellular localization results implied that BjuAOP2 proteins were mainly concentrated in the cytoplasm. Phylogenetic analysis of the AOP2 proteins from the sequenced Brassicaceae species in BRAD showed that BjuAOP2 genes were more closely linked to Brassica carinata and Brassica rapa than Arabidopsis. In comparison with other Brassicaceae plants, the BjuAOP2 members were conserved in terms of gene structures, protein sequences, and motifs. The light response and hormone response elements were included in the BjuAOP2 genes' cis-regulatory elements. The expression pattern of BjuAOP2 genes was influenced by the different stages of development and the type of tissue being examined. The BjuAOP2 proteins were used to perform the heterologous expression experiment. The results showed that all the five BjuAOP2 proteins can catalyze the conversion of GIB to SIN with different catalytic activity. These results provide the basis for further investigation of the functional study of BjuAOP2 in Tumorous stem mustard glucosinolate biosynthesis.
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Affiliation(s)
| | | | | | | | | | - Yihua Liu
- *Correspondence: Yihua Liu, ; Jingjing Chen,
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The Regulatory Effect of Phytochemicals on Chronic Diseases by Targeting Nrf2-ARE Signaling Pathway. Antioxidants (Basel) 2023; 12:antiox12020236. [PMID: 36829795 PMCID: PMC9952802 DOI: 10.3390/antiox12020236] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/15/2023] [Accepted: 01/17/2023] [Indexed: 01/22/2023] Open
Abstract
Redox balance is essential to maintain the body's normal metabolism. Once disrupted, it may lead to various chronic diseases, such as diabetes, neurodegenerative diseases, cardiovascular diseases, inflammatory diseases, cancer, aging, etc. Oxidative stress can cause or aggravate a series of pathological processes. Inhibition of oxidative stress and related pathological processes can help to ameliorate these chronic diseases, which have been found to be associated with Nrf2 activation. Nrf2 activation can not only regulate the expression of a series of antioxidant genes that reduce oxidative stress and its damage, but also directly regulate genes related to the above-mentioned pathological processes to counter the corresponding changes. Therefore, targeting Nrf2 has great potential for the prevention or treatment of chronic diseases, and many natural phytochemicals have been reported as Nrf2 activators although the defined mechanisms remain to be elucidated. This review article focuses on the possible mechanism of Nrf2 activation by natural phytochemicals in the prevention or treatment of chronic diseases and the regulation of oxidative stress. Moreover, the current clinical trials of phytochemical-originated drug discovery by targeting the Nrf2-ARE pathway were also summarized; the outcomes or the relationship between phytochemicals and chronic diseases prevention are finally analyzed to propose the future research strategies and prospective.
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Dietary Isothiocyanates: Novel Insights into the Potential for Cancer Prevention and Therapy. Int J Mol Sci 2023; 24:ijms24031962. [PMID: 36768284 PMCID: PMC9916827 DOI: 10.3390/ijms24031962] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/09/2023] [Accepted: 01/11/2023] [Indexed: 01/21/2023] Open
Abstract
Diet plays an important role in health. A high intake of plant chemicals such as glucosinolates/isothiocyanates can promote optimal health and decrease the risk of cancer. Recent research has discovered more novel mechanisms of action for the effects of isothiocyanates including the modulation of tumor microenvironment, the inhibition of the self-renewal of stem cells, the rearrangement of multiple pathways of energy metabolism, the modulation of microbiota, and protection against Helicobacter pylori. However, the hormetic/biphasic effects of isothiocyanates may make the recommendations complicated. Isothiocyanates possess potent anti-cancer activities based on up-to-date evidence from in vitro and in vivo studies. The nature of hormesis suggests that the benefits or risks of isothiocyanates largely depend on the dose and endpoint of interest. Isothiocyanates are a promising class of cancer-preventative phytochemicals, but researchers should be aware of the potential adverse (and hormetic) effects. In the authors' opinion, dietary isothiocyanates are better used as adjunctive treatments in combination with known anti-cancer drugs. The application of nano-formulations and the delivery of isothiocyanates are also discussed in this review.
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Brancaccio M, Milito A, Viegas CA, Palumbo A, Simes DC, Castellano I. First evidence of dermo-protective activity of marine sulfur-containing histidine compounds. Free Radic Biol Med 2022; 192:224-234. [PMID: 36174879 DOI: 10.1016/j.freeradbiomed.2022.09.017] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 09/06/2022] [Accepted: 09/17/2022] [Indexed: 10/31/2022]
Abstract
Among natural products, ovothiol (ovo), produced by marine invertebrates, bacteria, and microalgae, is receiving increasing interest for its unique antioxidant properties. Recently, ovo has been shown to exhibit anti-inflammatory activity in an in vitro model of endothelial dysfunction and in an in vivo model of liver fibrosis. The aim of this study was to evaluate the effect of ovo and its precursor 5-thiohistidine (5-thio) in comparison with ergothioneine (erg), in human skin cells and tissues upon inflammation. We used both an in vitro and ex vivo model of human skin, represented by a keratinocytes cell line (HaCaT) and skin biopsies, respectively. We observed that ovo, 5-thio, and erg were not cytotoxic in HaCaT cells, but instead exerted a protective function against TNF-α -induced inflammation. In order to get insights on their mechanism of action, we performed western blot analysis of ERK and JNK, as well as sub-cellular localization of Nrf2, a key mediator of the anti-inflammatory response. The results indicated that the pre-treatment with ovo, 5-thio, and erg differently affected the phosphorylation of ERK and JNK. However, all the three molecules promoted the accumulation of Nrf2 in the nucleus of HaCaT cells. In addition, gene expression analysis by RTqPCR and ELISA assays performed in ex vivo human skin tissues pre-treated with thiohistidines and then inflamed with IL-1β revealed a significant downregulation of IL-8, TNF-α and COX-2 genes and a concomitant significant decrease in the cytokines IL-6, IL-8 and TNF-α production. Moreover, the protective action of ovo and 5-thio resulted to be stronger when compared with dexamethasone, a corticosteroid drug currently used to treat skin inflammatory conditions. Our findings suggest that ovo and 5-thio can ameliorate skin damage and may be used to develop natural skin care products to prevent the inflammatory status induced by environmental stressors and aging.
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Affiliation(s)
- Mariarita Brancaccio
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131, Naples, Italy
| | - Alfonsina Milito
- Centre for Research in Agricultural Genomics - CRAG, Barcelona, Catalonia, Spain
| | - Carla Alexandra Viegas
- Centre of Marine Sciences (CCMAR), Universidade do Algarve, Faro, Portugal; GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), Universidade do Algarve, Faro, Portugal
| | - Anna Palumbo
- Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, Naples, Italy
| | - Dina Costa Simes
- Centre of Marine Sciences (CCMAR), Universidade do Algarve, Faro, Portugal; GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), Universidade do Algarve, Faro, Portugal
| | - Immacolata Castellano
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131, Naples, Italy; Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, Naples, Italy.
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Hwang M, Shrestha C, Kang S, Kim J. MEKK-3 Acts Cooperatively with NSY-1 in SKN-1-Dependent Manner against Oxidative Stress and Aging in Caenorhabditis elegans. BIOLOGY 2022; 11:biology11101526. [PMID: 36290429 PMCID: PMC9598901 DOI: 10.3390/biology11101526] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/15/2022] [Accepted: 10/17/2022] [Indexed: 11/15/2022]
Abstract
Oxidative stress resulting from reactive oxygen species and other toxic metabolites is involved in human diseases, and it plays an important role in aging. In Caenorhabditis elegans, SKN-1 is required for protection against oxidative stress and aging. As p38 mitogen-activated protein kinase signaling is activated in response to oxidative stress, SKN-1 accumulates in intestinal nuclei and induces phase II detoxification genes. However, NSY-1, a well-known mitogen-activated protein kinase kinase kinase (MAPKKK) of C. elegans, acts as a partial regulator of the SKN-1-induced oxidative stress signaling pathway, suggesting that the regulator for optimal activation of SKN-1 remains unknown. Here, we report a MAPKKK, MEKK-3, as a new regulator required for full activation of SKN-1-mediated resistance against oxidative stress and aging. In RNA-interference-based screening, we found that the simultaneous knockdown of mekk-3 and nsy-1 significantly decreased the oxidative stress resistance and survival of SKN-1 transgenic worms. MEKK-3 was induced in response to oxidative stress. Mechanistic analysis revealed that double knockdown of mekk-3 and nsy-1 completely suppressed the nuclear localization of SKN-1. These results were reproduced in mutant worms in which SKN-1 is constitutively localized to intestinal nuclei. In addition, mekk-3 and nsy-1 were required for optimal induction of SKN-1 target genes such as gcs-1 and trx-1. These data indicate that MEKK-3 plays an essential role in the SKN-1-dependent signaling pathway involved in oxidative stress resistance and longevity by cooperating with NSY-1.
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Affiliation(s)
- Min Hwang
- Department of Pharmacology, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
| | - Chandani Shrestha
- Department of Pharmacology, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
| | - Shinwon Kang
- Department of Physiology, University of Toronto, Toronto, ON M5S, Canada
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System, Toronto, ON M5G, Canada
| | - Jiyoon Kim
- Department of Pharmacology, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
- Correspondence:
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The KEAP1-NRF2 System and Esophageal Cancer. Cancers (Basel) 2022; 14:cancers14194702. [PMID: 36230622 PMCID: PMC9564177 DOI: 10.3390/cancers14194702] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 09/24/2022] [Accepted: 09/24/2022] [Indexed: 12/18/2022] Open
Abstract
NRF2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that regulates the expression of many cytoprotective genes. NRF2 activation is mainly regulated by KEAP1 (kelch-like ECH-associated protein 1) through ubiquitination and proteasome degradation. Esophageal cancer is classified histologically into two major types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). ESCC harbors more genetic alterations in the KEAP-NRF2 system than EAC does, which results in NRF2 activation in these cancers. NRF2-addicted ESCC exhibits increased malignancy and acquisition of resistance to chemoradiotherapy. Therefore, it has been recognized that the development of drugs targeting the KEAP1-NRF2 system based on the molecular dissection of NRF2 function is important and urgent for the treatment of ESCC, along with efficient clinical screening for NRF2-addicted ESCC patients. Recently, the fate of NRF2-activated cells in esophageal tissues, which was under the influence of strong cell competition, and its relationship to the pathogenesis of ESCC, was clarified. In this review, we will summarize the current knowledge of the KEAP1-NRF2 system and the treatment of ESCC. We propose three main strategies for the treatment of NRF2-addicted cancer: (1) NRF2 inhibitors, (2) synthetic lethal drugs for NRF2-addicted cancers, and (3) NRF2 inducers of the host defense system.
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Zhao Y, Shang S, Song Y, Li T, Han M, Qin Y, Wei M, Xi J, Tang B. Sulforaphane kills Mycobacterium tuberculosis H37Ra and Mycobacterium smegmatis mc2155 through a reactive oxygen species dependent mechanism. J Microbiol 2022; 60:1095-1105. [DOI: 10.1007/s12275-022-2284-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/09/2022] [Accepted: 08/22/2022] [Indexed: 10/14/2022]
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Glucosinolates and Omega-3 Fatty Acids from Mustard Seeds: Phytochemistry and Pharmacology. PLANTS 2022; 11:plants11172290. [PMID: 36079672 PMCID: PMC9459965 DOI: 10.3390/plants11172290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/29/2022] [Accepted: 08/30/2022] [Indexed: 11/22/2022]
Abstract
Seeds from mustard (genera Brassica spp. and Sinapsis spp.), are known as a rich source of glucosinolates and omega-3 fatty acids. These compounds are widely known for their health benefits that include reducing inflammation and lowering the risk of cardiovascular diseases and cancer. This review presented a synthesis of published literature from Google Scholar, PubMed, Scopus, Sci Finder, and Web of Science regarding the different glucosinolates and omega-3 fatty acids isolated from mustard seeds. We presented an overview of extraction, isolation, purification, and structure elucidation of glucosinolates from the seeds of mustard plants. Moreover, we presented a compilation of in vitro, in vivo, and clinical studies showing the potential health benefits of glucosinolates and omega-3 fatty acids. Previous studies showed that glucosinolates have antimicrobial, antipain, and anticancer properties while omega-3 fatty acids are useful for their pharmacologic effects against sleep disorders, anxiety, cerebrovascular disease, neurodegenerative disease, hypercholesterolemia, and diabetes. Further studies are needed to investigate other naturally occurring glucosinolates and omega-3 fatty acids, improve and standardize the extraction and isolation methods from mustard seeds, and obtain more clinical evidence on the pharmacological applications of glucosinolates and omega-3 fatty acids from mustard seeds.
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Negro EJ, Sendker J, Stark T, Lipowicz B, Hensel A. Phytochemical and functional analysis of horseradish (Armoracia rusticana) fermented and non-fermented root extracts. Fitoterapia 2022; 162:105282. [PMID: 35988845 DOI: 10.1016/j.fitote.2022.105282] [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: 05/24/2022] [Revised: 08/15/2022] [Accepted: 08/15/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND The roots of horseradish (Armoracia rusticana) are used for infections of respiratory airway and for urinary tract infections due to isothiocyanates (ITC), enzymatically formed during fermentation of glucosinolates by myrosinase. HYPOTHESIS/PURPOSE The present study aims to present a comprehensive overview on the phytochemical composition of A. rusticana roots, especially concerning isothiocyanates and respective glucosinolates. The complex flavonoid spectrum of the herbal material is reviewed. Published data on in vitro activity of horseradish extracts and isolated compounds are summarized. These data indicate well-established use of horseradish as an antibacterial remedy against bacterial infections of the airway and urinary tract. STUDY DESIGN To answer the question if other compounds from A. rusticana beside ITC contribute to the antibacterial activity, non-targeted LC-MS studies were performed with fermented and non-fermented horseradish extracts, and detailed phytochemical profiles were established. RESULTS Comparative investigations on the antibacterial activity indicated that only ITC-containing extracts and fractions exert antibacterial activity. The huge variety of non-ITC compounds do not significantly contribute to the antibacterial activity, but can be used for analytical characterisation and quality control of the herbal material. Detailed phytochemical analysis additionally revealed a variety of compounds, not described until now for horseradish roots: the flavonol glycosides kaempferol-3-O-β-d-xylopyranosyl-(1''' → 2'')-β-d-galactopyranoside, kaempferol-3-O-α-l-rhamnopyranosyl-(1''' → 6'')-β-d-glucopyranoside, kaempferol-3-O-β-d-glucopyranoside, Kaempferol-3-O-β-d-xylopyranosyl-7-O-β-d-glucopyranoside, Kaempferol-3-O-β-d-xylopyranosyl-(1'''' → 2''')-β-d-galactopyranoside-7-O-β-d-glucopyranoside, the oxo-indole derivative spirobrassinin, the phenylthiazole 2-methylsulfanyl-4-phenyl-4,5-dihydro-1,3-thiazole, a series of lysophophatidylethanolamine and 13 different N-phenylpropenoyl-L-amino acids. CONCLUSION The antibacterial effects of horseradish are only due to the presence of glucosinolates resp. the corresponding ITC, and the detailed overall composition of horseradish extracts has been reported.
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Affiliation(s)
- Elena Jimenez Negro
- University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Corrensstrasse 48, D-48149 Münster, Germany
| | - Jandirk Sendker
- University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Corrensstrasse 48, D-48149 Münster, Germany
| | - Timo Stark
- Technical University of München, Chair of Food Chemistry and Molecular Sensory Science, Lise-Meitner-Straße 34, D-85354 München, Germany
| | | | - Andreas Hensel
- University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Corrensstrasse 48, D-48149 Münster, Germany.
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Issues Related to the Treatment of H. pylori Infection in People Living with HIV and Receiving Antiretrovirals. Microorganisms 2022; 10:microorganisms10081541. [PMID: 36013959 PMCID: PMC9413132 DOI: 10.3390/microorganisms10081541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/20/2022] [Accepted: 07/22/2022] [Indexed: 02/04/2023] Open
Abstract
Treatment of Helicobacter pylori infection in people living with HIV is associated with several challenges, including those related to drug metabolism which plays a major role in treatment efficacy. In this review, we will discuss the enzymes involved in the metabolism of anti-Helicobacter pylori and anti-HIV drugs to provide a basis for understanding the potential for interactions between these drug classes. We will also provide a clinical perspective on other issues related to the treatment of Helicobacter pylori and HIV infections such as comorbidities, adherence, and peer communication. Finally, based on our understanding of the interplay between the above issues, we propose a new concept “Antimicrobial susceptibility testing-drug interaction-supports-referent physician” (AISR), to provide a framework for improving rates of H. pylori eradication in people living with HIV.
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Khodakarami A, Adibfar S, Karpisheh V, Abolhasani S, Jalali P, Mohammadi H, Gholizadeh Navashenaq J, Hojjat-Farsangi M, Jadidi-Niaragh F. The molecular biology and therapeutic potential of Nrf2 in leukemia. Cancer Cell Int 2022; 22:241. [PMID: 35906617 PMCID: PMC9336077 DOI: 10.1186/s12935-022-02660-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 07/19/2022] [Indexed: 02/07/2023] Open
Abstract
NF-E2-related factor 2 (Nrf2) transcription factor has contradictory roles in cancer, which can act as a tumor suppressor or a proto-oncogene in different cell conditions (depending on the cell type and the conditions of the cell environment). Nrf2 pathway regulates several cellular processes, including signaling, energy metabolism, autophagy, inflammation, redox homeostasis, and antioxidant regulation. As a result, it plays a crucial role in cell survival. Conversely, Nrf2 protects cancerous cells from apoptosis and increases proliferation, angiogenesis, and metastasis. It promotes resistance to chemotherapy and radiotherapy in various solid tumors and hematological malignancies, so we want to elucidate the role of Nrf2 in cancer and the positive point of its targeting. Also, in the past few years, many studies have shown that Nrf2 protects cancer cells, especially leukemic cells, from the effects of chemotherapeutic drugs. The present paper summarizes these studies to scrutinize whether targeting Nrf2 combined with chemotherapy would be a therapeutic approach for leukemia treatment. Also, we discussed how Nrf2 and NF-κB work together to control the cellular redox pathway. The role of these two factors in inflammation (antagonistic) and leukemia (synergistic) is also summarized.
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Affiliation(s)
- Atefeh Khodakarami
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sara Adibfar
- Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Vahid Karpisheh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shiva Abolhasani
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Pooya Jalali
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamed Mohammadi
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | | | - Mohammad Hojjat-Farsangi
- Bioclinicum, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.,Department of Immunology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Farhad Jadidi-Niaragh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. .,Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. .,Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
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Hoffmann H, Ott C, Raupbach J, Andernach L, Renz M, Grune T, Hanschen FS. Assessing Bioavailability and Bioactivity of 4-Hydroxythiazolidine-2-Thiones, Newly Discovered Glucosinolate Degradation Products Formed During Domestic Boiling of Cabbage. Front Nutr 2022; 9:941286. [PMID: 35938125 PMCID: PMC9354954 DOI: 10.3389/fnut.2022.941286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 06/15/2022] [Indexed: 11/19/2022] Open
Abstract
Glucosinolates are plant secondary metabolites found in cruciferous vegetables (Brassicaceae) that are valued for their potential health benefits. Frequently consumed representatives of these vegetables, for example, are white or red cabbage, which are typically boiled before consumption. Recently, 3-alk(en)yl-4-hydroxythiazolidine-2-thiones were identified as a class of thermal glucosinolate degradation products that are formed during the boiling of cabbage. Since these newly discovered compounds are frequently consumed, this raises questions about their potential uptake and their possible bioactive functions. Therefore, 3-allyl-4-hydroxythiazolidine-2-thione (allyl HTT) and 4-hydroxy-3-(4-(methylsulfinyl) butyl)thiazolidine-2-thione (4-MSOB HTT) as degradation products of the respective glucosinolates sinigrin and glucoraphanin were investigated. After consumption of boiled red cabbage broth, recoveries of consumed amounts of the degradation products in urine collected for 24 h were 18 ± 5% for allyl HTT and 21 ± 4% for 4-MSOB HTT (mean ± SD, n = 3). To investigate the stability of the degradation products during uptake and to elucidate the uptake mechanism, both an in vitro stomach and an in vitro intestinal model were applied. The results indicate that the uptake of allyl HTT and 4-MSOB HTT occurs by passive diffusion. Both compounds show no acute cell toxicity, no antioxidant potential, and no change in NAD(P)H dehydrogenase quinone 1 (NQO1) activity up to 100 μM. However, inhibition of glycogen synthase kinases-3 (GSK-3) in the range of 20% for allyl HTT for the isoform GSK-3β and 29% for 4-MSOB HTT for the isoform GSK-3α at a concentration of 100 μM was found. Neither health-promoting nor toxic effects of 3-alk(en)yl-4-hydroxythiazolidine-2-thiones were found in the four tested assays carried out in this study, which contrasts with the properties of other glucosinolate degradation products, such as isothiocyanates.
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Affiliation(s)
- Holger Hoffmann
- Plant Quality and Food Security, Leibniz Institute of Vegetable and Ornamental Crops (IGZ), Großbeeren, Germany
| | - Christiane Ott
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany
| | - Jana Raupbach
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany
| | - Lars Andernach
- Plant Quality and Food Security, Leibniz Institute of Vegetable and Ornamental Crops (IGZ), Großbeeren, Germany
| | - Matthias Renz
- Plant Quality and Food Security, Leibniz Institute of Vegetable and Ornamental Crops (IGZ), Großbeeren, Germany
| | - Tilman Grune
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany
- Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
- Department of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
| | - Franziska S. Hanschen
- Plant Quality and Food Security, Leibniz Institute of Vegetable and Ornamental Crops (IGZ), Großbeeren, Germany
- *Correspondence: Franziska S. Hanschen
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Bayo Jimenez MT, Frenis K, Hahad O, Steven S, Cohen G, Cuadrado A, Münzel T, Daiber A. Protective actions of nuclear factor erythroid 2-related factor 2 (NRF2) and downstream pathways against environmental stressors. Free Radic Biol Med 2022; 187:72-91. [PMID: 35613665 DOI: 10.1016/j.freeradbiomed.2022.05.016] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 04/23/2022] [Accepted: 05/19/2022] [Indexed: 12/14/2022]
Abstract
Environmental risk factors, including noise, air pollution, chemical agents, ultraviolet radiation (UVR) and mental stress have a considerable impact on human health. Oxidative stress and inflammation are key players in molecular pathomechanisms of environmental pollution and risk factors. In this review, we delineate the impact of environmental risk factors and the protective actions of the nuclear factor erythroid 2-related factor 2 (NRF2) in connection to oxidative stress and inflammation. We focus on well-established studies that demonstrate the protective actions of NRF2 and its downstream pathways against different environmental stressors. State-of-the-art mechanistic considerations on NRF2 signaling are discussed in detail, e.g. classical concepts like KEAP1 oxidation/electrophilic modification, NRF2 ubiquitination and degradation. Specific focus is also laid on NRF2-dependent heme oxygenase-1 induction with detailed presentation of the protective down-stream pathways of heme oxygenase-1, including interaction with BACH1 system. The significant impact of all environmental stressors on the circadian rhythm and the interactions of NRF2 with the circadian clock will also be considered here. A broad range of NRF2 activators is discussed in relation to environmental stressor-induced health side effects, thereby suggesting promising new mitigation strategies (e.g. by nutraceuticals) to fight the negative effects of the environment on our health.
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Affiliation(s)
- Maria Teresa Bayo Jimenez
- Department of Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Katie Frenis
- Department of Hematology and Oncology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA, 02115, USA
| | - Omar Hahad
- Department of Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, Langenbeckstraße 1, 55131, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany; Leibniz Insitute for Resilience Research (LIR), Mainz, Germany
| | - Sebastian Steven
- Department of Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Guy Cohen
- The Skin Research Institute, The Dead Sea and Arava Science Center, Masada, 86910, Israel; Ben Gurion University of the Negev, Eilat Campus, Eilat, 8855630, Israel
| | - Antonio Cuadrado
- Departamento de Bioquímica, Facultad de Medicina, Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Investigación Sanitaria La Paz (IdiPaz), Instituto de Investigaciones Biomédicas 'Alberto Sols' UAM-CSIC, Universidad Autónoma de Madrid, Madrid, Spain
| | - Thomas Münzel
- Department of Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, Langenbeckstraße 1, 55131, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany.
| | - Andreas Daiber
- Department of Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, Langenbeckstraße 1, 55131, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany.
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Zhang G, Kang Y, Cathey D, LeBlanc AJ, Cai J, Cai L, Wang S, Huang J, Keller BB. Sulforaphane Does Not Protect Right Ventricular Systolic and Diastolic Functions in Nrf2 Knockout Pulmonary Artery Hypertension Mice. Cardiovasc Drugs Ther 2022; 36:425-436. [PMID: 35157168 PMCID: PMC9091145 DOI: 10.1007/s10557-022-07323-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/02/2022] [Indexed: 12/22/2022]
Abstract
PURPOSE Nrf2 is a nuclear transcription factor and plays an important role in the regulation of oxidative stress and inflammation. We recently demonstrated that sulforaphane (SFN) protected mice from developing pulmonary arterial hypertension (PAH) and right ventricular (RV) dysfunction by elevating cardiac Nrf2 expression and function. Here we further investigate Nrf2 dependence for SFN-mediated prevention of PAH and RV dysfunction in an Nrf2 knockout mouse model. METHODS We used male global Nrf2-knockout mice and male C57/6 J wild type mice in the following groups: Control group received room air and vehicle control; SuHx group received SU5416 and 10% hypoxia for 4 weeks to induce PAH; SuHx+SFN group received both SuHx and sulforaphane, a Nrf2 activator, for 4 weeks. Transthoracic echocardiography was performed to quantify RV function and estimate pulmonary vascular resistance over 4 weeks. PAH was confirmed using invasive RV systolic pressure measurement at 4 weeks. RESULTS All Nrf2 knockout mice survived the 4-week SuHx induction of PAH. SuHx caused progressive RV diastolic/systolic dysfunction and increased RV systolic pressure. The development of RV diastolic dysfunction occurred earlier in the Nrf2 knockout PAH mice when compared with the wide type PAH mice. SFN partially or completely reversed SuHx-induced RV diastolic/systolic dysfunction and increased RV systolic pressure in wild-type mice, but not in Nrf2 knockout mice. CONCLUSION Our findings demonstrated the essential role of Nrf2 in SFN-mediated prevention of RV dysfunction and PAH, and increasing Nrf2 activity in patients with PAH may have therapeutic potential.
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Affiliation(s)
- Guangyan Zhang
- Department of Anesthesiology and Perioperative Medicine, University of Louisville, 530 South Jackson Street, Louisville, KY USA
- Department of Anesthesiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Pediatric Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY USA
| | - Yin Kang
- Department of Anesthesiology and Perioperative Medicine, University of Louisville, 530 South Jackson Street, Louisville, KY USA
- Department of Anesthesiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Pediatric Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY USA
| | - Dakotah Cathey
- Department of Anesthesiology and Perioperative Medicine, University of Louisville, 530 South Jackson Street, Louisville, KY USA
| | - Amanda J. LeBlanc
- Cardiovascular Innovation Institute, Department of Cardiovascular and Thoracic Surgery, University of Louisville, Louisville, KY USA
| | - Jun Cai
- Pediatric Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY USA
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY USA
| | - Lu Cai
- Pediatric Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY USA
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY USA
| | - Sheng Wang
- Department of Anesthesiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Department of Anesthesiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Jiapeng Huang
- Department of Anesthesiology and Perioperative Medicine, University of Louisville, 530 South Jackson Street, Louisville, KY USA
- Cardiovascular Innovation Institute, Department of Cardiovascular and Thoracic Surgery, University of Louisville, Louisville, KY USA
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY USA
- Department of Medicine, University of Louisville, Louisville, KY USA
| | - Bradley B. Keller
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY USA
- Kosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, Department of Pediatrics, University of Louisville, School of Medicine, Louisville, KY USA
- Present Address: Cincinnati Children’s Heart Institute, Greater Louisville and Western Kentucky Practice, Louisville, KY USA
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Li H, Wu Q, Liu Q, Jin L, Chen B, Li C, Xiao J, Shen Y. Volatile Flavor Compounds of Pugionium cornutum (L.) Gaertn. Before and After Different Dehydration Treatments. Front Nutr 2022; 9:884086. [PMID: 35586736 PMCID: PMC9108931 DOI: 10.3389/fnut.2022.884086] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 04/01/2022] [Indexed: 12/02/2022] Open
Abstract
Pugionium cornutum (L.) Gaertn (also Pugionium) is a special Mongolian vegetable, belonging to the Cruciferous family, growing in arid and semi-arid areas of northern China, with a unique flavor and potential health benefits. This article aims to describe the profile of volatile flavor compounds in fresh and different dehydrated samples, establish the fingerprint, and identify the characteristic compounds. The fresh Pugionium sample and 3 kinds of dehydrated samples were analyzed. Headspace/gas chromatography-ion migration spectrometry (HS/GC-IMS) and solid-phase microextraction/gas chromatography-mass spectrometry (SPME/GC-MS) were used for identification and relative quantification. HS/GC-IMS identified 78 compounds, whereas SPME/GC-MS identified 53 compounds. Principal component analysis (PCA), clustering analysis, and partial least squares discriminant analysis (PLS-DA) were used as appropriate to investigate variations in volatile compounds among Pugionium samples and identify distinctive compounds. The first two principal components described 76.5% and 69.5% of the variance of the data from HS/GC-IMS and SPME/GC-MS, respectively. By clustering analysis, 4 kinds of Pugionium samples could be classified into four independent groups. The similarity between fresh Pugionium and natural dehydration Pugionium was higher than the other two dehydrated samples, indicating that natural dehydration can better preserve the flavor of Pugionium. Most aldehydes and alcohols increased following different dehydration procedures, whereas esters decreased, and the dehydrated Pugionium samples have more harmonious and less pungent aroma than the fresh Pugionium. PLS-DA model analysis revealed that the marker compounds (VIP scores > 1) discriminating the flavor of the four samples for HS/GC-IMS and SPME/GC-MS were 24 and 15 compounds, respectively, such as 2-phenylethyl isothiocyanate, 1-butene-4-isothiocyanate and other isothiocyanates, 2-propanone, nonanal, gamma-butyrolactone, 2,3-butanediol, 3-methyl-2-butenenitrile, and pentanal. Analysis of volatile compounds might be useful for monitoring the quality of Pugionium and guiding the cooking methods and processing technologies. More study is required to discover if the various volatile flavor compounds have biological or physiological impacts on nutrition.
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Affiliation(s)
- Haoyu Li
- Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, National Demonstration Center for Experimental Chemistry Education, Northwest University, Xi'an, China
- Shaanxi Key Laboratory of Chemical Reaction Engineering, College of Chemistry and Chemical Engineering, Yan'an University, Yan'an, China
| | - Qian Wu
- Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, National Demonstration Center for Experimental Chemistry Education, Northwest University, Xi'an, China
| | - Qiannan Liu
- Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, National Demonstration Center for Experimental Chemistry Education, Northwest University, Xi'an, China
| | - Lihua Jin
- Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, National Demonstration Center for Experimental Chemistry Education, Northwest University, Xi'an, China
| | - Bang Chen
- Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, National Demonstration Center for Experimental Chemistry Education, Northwest University, Xi'an, China
| | - Cong Li
- Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, National Demonstration Center for Experimental Chemistry Education, Northwest University, Xi'an, China
- *Correspondence: Cong Li
| | - Jianbo Xiao
- Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo-Ourense, Ourense, Spain
| | - Yehua Shen
- Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, National Demonstration Center for Experimental Chemistry Education, Northwest University, Xi'an, China
- Yehua Shen
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Kumar H, Kumar RM, Bhattacharjee D, Somanna P, Jain V. Role of Nrf2 Signaling Cascade in Breast Cancer: Strategies and Treatment. Front Pharmacol 2022; 13:720076. [PMID: 35571115 PMCID: PMC9098811 DOI: 10.3389/fphar.2022.720076] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 03/31/2022] [Indexed: 12/30/2022] Open
Abstract
Breast cancer is the second leading cancer among all types of cancers. It accounts for 12% of the total cases of cancers. The complex and heterogeneous nature of breast cancer makes it difficult to treat in advanced stages. The expression of various enzymes and proteins is regulated by several molecular pathways. Oxidative stress plays a vital role in cellular events that are generally regulated by nuclear factor erythroid 2-related factor 2 (Nrf2). The exact mechanism of Nrf2 behind cytoprotective and antioxidative properties is still under investigation. In healthy cells, Nrf2 expression is lower, which maintains antioxidative stress; however, cancerous cells overexpress Nrf2, which is associated with various phenomena, such as the development of drug resistance, angiogenesis, development of cancer stem cells, and metastasis. Aberrant Nrf2 expression diminishes the toxicity and potency of therapeutic anticancer drugs and provides cytoprotection to cancerous cells. In this article, we have discussed the attributes associated with Nrf2 in the development of drug resistance, angiogenesis, cancer stem cell generation, and metastasis in the specific context of breast cancer. We also discussed the therapeutic strategies employed against breast cancer exploiting Nrf2 signaling cascades.
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Affiliation(s)
| | | | | | | | - Vikas Jain
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India
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Janczewski Ł. Sulforaphane and Its Bifunctional Analogs: Synthesis and Biological Activity. Molecules 2022; 27:1750. [PMID: 35268851 PMCID: PMC8911885 DOI: 10.3390/molecules27051750] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 03/04/2022] [Accepted: 03/05/2022] [Indexed: 12/27/2022] Open
Abstract
For decades, various plants have been studied as sources of biologically active compounds. Compounds with anticancer and antimicrobial properties are the most frequently desired. Cruciferous plants, including Brussels sprouts, broccoli, and wasabi, have a special role in the research studies. Studies have shown that consumption of these plants reduce the risk of lung, breast, and prostate cancers. The high chemopreventive and anticancer potential of cruciferous plants results from the presence of a large amount of glucosinolates, which, under the influence of myrosinase, undergo an enzymatic transformation to biologically active isothiocyanates (ITCs). Natural isothiocyanates, such as benzyl isothiocyanate, phenethyl isothiocyanate, or the best-tested sulforaphane, possess anticancer activity at all stages of the carcinogenesis process, show antibacterial activity, and are used in organic synthesis. Methods of synthesis of sulforaphane, as well as its natural or synthetic bifunctional analogues with sulfinyl, sulfanyl, sulfonyl, phosphonate, phosphinate, phosphine oxide, carbonyl, ester, carboxamide, ether, or additional isothiocyanate functional groups, and with the unbranched alkyl chain containing 2-6 carbon atoms, are discussed in this review. The biological activity of these compounds are also reported. In the first section, glucosinolates, isothiocyanates, and mercapturic acids (their metabolites) are briefly characterized. Additionally, the most studied anticancer and antibacterial mechanisms of ITC actions are discussed.
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Affiliation(s)
- Łukasz Janczewski
- Faculty of Chemistry, Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland
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Castro I, André-Barrès C, Fabre N, Massou S, Sauvain M, Pareja DC, Jullian V. Cordiasecosides G-J, 9,10-Seco-29-norcycloartane glycosides isolated from Cordia lutea and their antibacterial activities. Fitoterapia 2022; 158:105172. [DOI: 10.1016/j.fitote.2022.105172] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 03/07/2022] [Accepted: 03/08/2022] [Indexed: 11/26/2022]
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Bai Y, Feldman C, Li Y, Keys K, Overgaard K. A Functional Vegetable Option: An Exploratory Study Testing Kimchi Variation for Acceptance among Consumers. JOURNAL OF CULINARY SCIENCE & TECHNOLOGY 2021. [DOI: 10.1080/15428052.2020.1790075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Affiliation(s)
- Yeon Bai
- Department of Nutrition and Food Studies, Montclair State University, Montclair, New Jersey, USA
| | - Charles Feldman
- Department of Nutrition and Food Studies, Montclair State University, Montclair, New Jersey, USA
| | - Yanyan Li
- College of Science and Humanities, Husson University, Bangor, Maine, USA
| | - Ki Keys
- Department of Nutrition and Food Studies, Montclair State University, Montclair, New Jersey, USA
| | - Kaitlin Overgaard
- Department of Nutrition and Food Studies, Montclair State University, Montclair, New Jersey, USA
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50
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Kang S, Guo Y, Rao J, Jin H, You HJ, Ji GE. In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus plantarum pH3A, monolaurin, and grapefruit seed extract. Food Funct 2021; 12:11024-11032. [PMID: 34657941 DOI: 10.1039/d1fo01480c] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori infection is the most common cause of gastritis and gastric ulcers. Considering the severe side effects of current antibiotic therapies, it is crucial to find an alternate treatment for H. pylori infection. In this study, we investigated the anti-H. pylori effects of a newly isolated strain of Lactobacillus plantarum (pH3A), monolaurin, grapefruit seed extract (GSE), and their synergies in vitro and in vivo. Monolaurin and GSE suppressed H. pylori growth and urease activity at a minimal inhibitory concentration (MIC) of 62.5 ppm. Live cells and cell-free culture supernatant (CFCS) of L. plantarum pH3A with or without pH adjustment also significantly inhibited H. pylori growth. Although synergy was not observed between monolaurin and GSE, the addition of CFCS significantly enhanced their anti-H. pylori activities. Moreover, L. plantarum pH3A significantly decreased the ability of H. pylori to adhere to AGS cells and interleukin (IL)-8 production in the H. pylori-stimulated AGS cell line. The addition of GSE or monolaurin strengthened these effects. In the in vivo study, H. pylori colonization of the mouse stomach and total serum IgG production were significantly reduced by L. plantarum pH3A treatment, but the addition of monolaurin or GSE did not contribute to these anti-H. pylori activities. Therefore, the L. plantarum pH3A strain can potentially be applied as an alternative anti-H. pylori therapy, but evidence of its synergy with monolaurin or GSE in vivo is still lacking.
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Affiliation(s)
- Sini Kang
- Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Key Laboratory of Industrial Microbiology, National "111'' Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Research Center of Food Fermentation Engineering and Technology, Hubei University of Technology, Wuhan 430068, China. .,Department of Food and Nutrition, Research Institute of Human Ecology, Seoul National University, Seoul 08826, Korea.
| | - Yaqing Guo
- Department of Food and Nutrition, Research Institute of Human Ecology, Seoul National University, Seoul 08826, Korea.
| | - Junhui Rao
- Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Key Laboratory of Industrial Microbiology, National "111'' Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Research Center of Food Fermentation Engineering and Technology, Hubei University of Technology, Wuhan 430068, China.
| | - Hui Jin
- Department of Food and Nutrition, Research Institute of Human Ecology, Seoul National University, Seoul 08826, Korea.
| | - Hyun Ju You
- Bio-MAX/N-BIO, Seoul National University, Seoul 08826, Korea.
| | - Geun Eog Ji
- Department of Food and Nutrition, Research Institute of Human Ecology, Seoul National University, Seoul 08826, Korea. .,Research Center, BIFIDO Co., Ltd, Hongcheon 25117, Korea.
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