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Askarizadeh F, Butler AE, Kesharwani P, Sahebkar A. Regulatory effect of curcumin on CD40:CD40L interaction and therapeutic implications. Food Chem Toxicol 2025; 200:115369. [PMID: 40043936 DOI: 10.1016/j.fct.2025.115369] [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: 11/14/2024] [Revised: 01/24/2025] [Accepted: 03/02/2025] [Indexed: 04/21/2025]
Abstract
Natural compounds have garnered significant attention as potential therapeutic agents due to their inherent properties. Their notable qualities, including safety, efficacy, favorable pharmacokinetic properties, and heightened effectiveness against certain diseases, particularly inflammatory conditions, make them particularly appealing. Among these compounds, curcumin has attracted considerable interest for its unique therapeutic properties and has therefore been extensively studied as a potential therapeutic agent for treating various diseases. Curcumin exhibits diverse anti-inflammatory, antioxidant, and antimicrobial effects. Curcumin's immune system regulatory ability has made it a promising compound for treatment of various inflammatory diseases, such as psoriasis, atherosclerosis, asthma, colitis, IBD, and arthritis. Among the signaling pathways implicated in these conditions, the CD40 receptor together with its ligand, CD40L, are recognized as central players. Studies have demonstrated that the interaction between CD40 and CD40L interaction acts as the primary mediator of the immune response in inflammatory diseases. Numerous studies have explored the impact of curcumin on the CD40:CD40L pathway, highlighting its regulatory effects on this inflammatory pathway and its potential therapeutic use in related inflammatory conditions. In this review, we will consider the evidence concerning curcumin's modulatory effects in inflammatory disease and its potential therapeutic role in regulating the CD40:CD40L pathway.
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Affiliation(s)
- Fatemeh Askarizadeh
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.
| | - Amirhossein Sahebkar
- Center for Global Health Research, Saveetha Institute of Medical and Technical Sciences, Saveetha Medical College and Hospitals, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Yang H, Zhang H, Tian L, Guo P, Liu S, Chen H, Sun L. Curcumin attenuates lupus nephritis by inhibiting neutrophil migration via PI3K/AKT/NF-κB signalling pathway. Lupus Sci Med 2024; 11:e001220. [PMID: 39053932 DOI: 10.1136/lupus-2024-001220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 07/12/2024] [Indexed: 07/27/2024]
Abstract
OBJECTIVE To investigate the role of curcumin in the treatment of lupus nephritis (LN) by inhibiting the migration of neutrophils and the underlying mechanism involved. METHODS Two lupus mouse models, MRL/lpr mice and R848-treated mice, were treated with 50 mg/kg curcumin by intraperitoneal injection. H&E and Masson staining were used to estimate histopathological changes in the kidney. Immunofluorescence was used to assess the deposition of immune complexes. The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription polymerase reaction (RT-PCR), and the protein expression was detected by western blotting. RESULTS We revealed the remarkable potential of curcumin in improving inflammatory conditions in both MRL/lpr mice and R848-induced lupus mice. Curcumin effectively decelerates the progression of inflammation and diminishes the infiltration of neutrophils and their release of pivotal inflammatory factors, thereby reducing inflammation in renal tissues. Mechanistically, curcumin significantly inhibits the expression of p-PI3K, p-AKT and p-NF-κB, which are upregulated by interleukin-8 to induce neutrophil migration and renal inflammation, thereby reducing neutrophil migration and the release of inflammatory factors. CONCLUSION Curcumin significantly inhibits the recruitment of neutrophils and the release of proinflammatory factors in the kidney by inhibiting the PI3K/AKT/NF-κB signalling pathway, providing new therapeutic targets and medication strategies for the treatment of LN.
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Affiliation(s)
- Hui Yang
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Haiwei Zhang
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing, Jiangsu, China
| | - Lili Tian
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Panpan Guo
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Shanshan Liu
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Hongwei Chen
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Lingyun Sun
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
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Qin T, Chen X, Meng J, Guo Q, Xu S, Hou S, Yuan Z, Zhang W. The role of curcumin in the liver-gut system diseases: from mechanisms to clinical therapeutic perspective. Crit Rev Food Sci Nutr 2023; 64:8822-8851. [PMID: 37096460 DOI: 10.1080/10408398.2023.2204349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2023]
Abstract
Natural products have provided abundant sources of lead compounds for new drug discovery and development over the past centuries. Curcumin is a lipophilic polyphenol isolated from turmeric, a plant used in traditional Asian medicine for centuries. Despite the low oral bioavailability, curcumin exhibits profound medicinal value in various diseases, especially liver and gut diseases, bringing an interest in the paradox of its low bioavailability but high bioactivity. Several latest studies suggest that curcumin's health benefits may rely on its positive gastrointestinal effects rather than its poor bioavailability solely. Microbial antigens, metabolites, and bile acids regulate metabolism and immune responses in the intestine and liver, suggesting the possibility that the liver-gut axis bidirectional crosstalk controls gastrointestinal health and diseases. Accordingly, these pieces of evidence have evoked great interest in the curcumin-mediated crosstalk among liver-gut system diseases. The present study discussed the beneficial effects of curcumin against common liver and gut diseases and explored the underlying molecular targets, as well as collected evidence from human clinical studies. Moreover, this study summarized the roles of curcumin in complex metabolic interactions in liver and intestine diseases supporting the application of curcumin in the liver-gut system as a potential therapeutic option, which opens an avenue for clinical use in the future.
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Affiliation(s)
- Tingting Qin
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Xiuying Chen
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Jiahui Meng
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Qianqian Guo
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Shan Xu
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Shanshan Hou
- Department of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, China
| | - Ziqiao Yuan
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Wenzhou Zhang
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
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Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects. Metabolites 2023; 13:metabo13010096. [PMID: 36677021 PMCID: PMC9862976 DOI: 10.3390/metabo13010096] [Citation(s) in RCA: 66] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 12/23/2022] [Accepted: 01/05/2023] [Indexed: 01/11/2023] Open
Abstract
Inflammatory bowel diseases (IBD) are chronic relapsing idiopathic inflammatory conditions affecting the gastrointestinal tract. They are mainly represented by two forms, ulcerative colitis (UC) and Crohn's disease (CD). IBD can be associated with the activation of nuclear factors, such as nuclear factor-kB (NF-kB), leading to increased transcription of pro-inflammatory mediators that result in diarrhea, abdominal pain, bleeding, and many extra-intestinal manifestations. Phytochemicals can interfere with many inflammation targets, including NF-kB pathways. Thus, this review aimed to investigate the effects of different phytochemicals in the NF-kB pathways in vitro and in vivo models of IBD. Fifty-six phytochemicals were included in this study, such as curcumin, resveratrol, kaempferol, sesamol, pinocembrin, astragalin, oxyberberine, berberine hydrochloride, botulin, taxifolin, naringin, thymol, isobavachalcone, lancemaside A, aesculin, tetrandrine, Ginsenoside Rk3, mangiferin, diosgenin, theanine, tryptanthrin, lycopene, gyngerol, alantolactone, mangostin, ophiopogonin D, fisetin, sinomenine, piperine, oxymatrine, euphol, artesunate, galangin, and nobiletin. The main observed effects related to NF-kB pathways were reductions in tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2), and augmented occludin, claudin-1, zonula occludens-1, and IL-10 expression levels. Moreover, phytochemicals can improve weight loss, stool consistency, and rectal bleeding in IBD. Therefore, phytochemicals can constitute a powerful treatment option for IBD in humans.
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Astorga J, Gasaly N, Dubois-Camacho K, De la Fuente M, Landskron G, Faber KN, Urra FA, Hermoso MA. The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD. Front Immunol 2022; 13:1028953. [PMID: 36466902 PMCID: PMC9716353 DOI: 10.3389/fimmu.2022.1028953] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 10/26/2022] [Indexed: 10/15/2023] Open
Abstract
Inflammatory Bowel Disease (IBD) is characterized by a loss of intestinal barrier function caused by an aberrant interaction between the immune response and the gut microbiota. In IBD, imbalance in cholesterol homeostasis and mitochondrial bioenergetics have been identified as essential events for activating the inflammasome-mediated response. Mitochondrial alterations, such as reduced respiratory complex activities and reduced production of tricarboxylic acid (TCA) cycle intermediates (e.g., citric acid, fumarate, isocitric acid, malate, pyruvate, and succinate) have been described in in vitro and clinical studies. Under inflammatory conditions, mitochondrial architecture in intestinal epithelial cells is dysmorphic, with cristae destruction and high dynamin-related protein 1 (DRP1)-dependent fission. Likewise, these alterations in mitochondrial morphology and bioenergetics promote metabolic shifts towards glycolysis and down-regulation of antioxidant Nuclear erythroid 2-related factor 2 (Nrf2)/Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling. Although the mechanisms underlying the mitochondrial dysfunction during mucosal inflammation are not fully understood at present, metabolic intermediates and cholesterol may act as signals activating the NLRP3 inflammasome in IBD. Notably, dietary phytochemicals exhibit protective effects against cholesterol imbalance and mitochondrial function alterations to maintain gastrointestinal mucosal renewal in vitro and in vivo conditions. Here, we discuss the role of cholesterol and mitochondrial metabolism in IBD, highlighting the therapeutic potential of dietary phytochemicals, restoring intestinal metabolism and function.
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Affiliation(s)
- Jessica Astorga
- Laboratory of Innate Immunity, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Naschla Gasaly
- Laboratory of Innate Immunity, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, Netherlands
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, Netherlands
| | - Karen Dubois-Camacho
- Laboratory of Innate Immunity, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile
- Laboratory of Metabolic Plasticity and Bioenergetics, Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Marjorie De la Fuente
- Laboratory of Biomedicine Research, School of Medicine, Universidad Finis Terrae, Santiago, Chile
| | - Glauben Landskron
- Laboratory of Biomedicine Research, School of Medicine, Universidad Finis Terrae, Santiago, Chile
| | - Klaas Nico Faber
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, Netherlands
| | - Félix A. Urra
- Laboratory of Metabolic Plasticity and Bioenergetics, Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Marcela A. Hermoso
- Laboratory of Innate Immunity, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, Netherlands
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Zhang Z, Cui Y, Liu S, Huang J, Liu Y, Zhou Y, Zhu Z. Short-term treatment with zingerone ameliorates dextran sulfate sodium-induced mouse experimental colitis. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2022; 102:4873-4882. [PMID: 35246845 DOI: 10.1002/jsfa.11850] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 02/12/2022] [Accepted: 03/04/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Ulcerative colitis (UC) is a relapsing and chronic inflammatory disease of the gastrointestinal tract, which seriously threatens human health. Zingerone (ZO) has been proven to be effective for many diseases. The purpose of this study is to investigate the protective effects and potential mechanisms of ZO extracted from ginger on dextran sulfate sodium (DSS)-induced mouse ulcerative colitis (UC). RESULTS The results showed that ZO alleviated the weight loss of UC model mice, reduced the disease activity index scores, and inhibited the shortening of colon length. ZO also improved DSS-induced pathological changes in colon tissue and inhibited the secretion of pro-inflammatory cytokines in colon and mesenteric lymph nodes. Further mechanism analysis found that ZO inhibited DSS-induced nuclear factor-κB pathway activation, and regulated peroxisome proliferator-activated receptor γ (PPARγ) expression. To further explore whether PPARγ was involved in the anti-UC effect of ZO, PPARγ inhibitor GW9662 was used. Although ZO also showed a protective effect on GW9662-treated colitis mice, the protective role was significantly weakened. Importantly, the administration of GW9662 significantly aggravated UC compared with the ZO + DSS group. In addition, we preliminarily found that ZO had the effects of inhibiting DSS-induced oxidative stress, maintaining intestinal barrier, and inhibiting the content of LPS and the population of Escherichia coli. CONCLUSIONS These results indicated that supplementation with ZO might be a new dietary strategy for the treatment of UC. © 2022 Society of Chemical Industry.
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Affiliation(s)
- Zecai Zhang
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
- Heilongjiang Provincial Technology Innovation Center for Bovine Disease Control and Prevention, Daqing, China
- Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, Daqing, China
- Heilongjiang Province Cultivating Collaborative Innovation Center for The Beidahuang Modern Agricultural Industry Technology, Daqing, China
| | - Yueqi Cui
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
- Heilongjiang Provincial Technology Innovation Center for Bovine Disease Control and Prevention, Daqing, China
| | - Siyu Liu
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
- Heilongjiang Provincial Technology Innovation Center for Bovine Disease Control and Prevention, Daqing, China
| | - Jiang Huang
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
- Heilongjiang Provincial Technology Innovation Center for Bovine Disease Control and Prevention, Daqing, China
| | - Yu Liu
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
- Heilongjiang Provincial Technology Innovation Center for Bovine Disease Control and Prevention, Daqing, China
- Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, Daqing, China
- Heilongjiang Province Cultivating Collaborative Innovation Center for The Beidahuang Modern Agricultural Industry Technology, Daqing, China
| | - Yulong Zhou
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
- Heilongjiang Provincial Technology Innovation Center for Bovine Disease Control and Prevention, Daqing, China
- Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, Daqing, China
- Heilongjiang Province Cultivating Collaborative Innovation Center for The Beidahuang Modern Agricultural Industry Technology, Daqing, China
| | - Zhanbo Zhu
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
- Heilongjiang Provincial Technology Innovation Center for Bovine Disease Control and Prevention, Daqing, China
- Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, Daqing, China
- Heilongjiang Province Cultivating Collaborative Innovation Center for The Beidahuang Modern Agricultural Industry Technology, Daqing, China
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Zheng S, Xue T, Wang B, Guo H, Liu Q. Chinese Medicine in the Treatment of Ulcerative Colitis: The Mechanisms of Signaling Pathway Regulations. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2022; 50:1781-1798. [PMID: 35950375 DOI: 10.1142/s0192415x22500756] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Ulcerative colitis (UC) is a common clinical inflammatory bowel disease characterized by repeated attacks, difficult treatment, and great harm to the physical and mental health of the patients. The occurrence and development of UC were closely related to the physiological and pathological processes, such as intestinal inflammatory reaction, oxidizing reaction, and immune response. Treatment of ulcerative colitis using Western medicine is often associated with a number of limitations and adverse events. There is a long history of using traditional Chinese medicine in dealing with this medical condition. Commonly used traditional Chinese medicines for the treatment of UC include Caulis Sargentodoxae, Flos Lonicerae, Fructus Cnidii, etc. Additionally, classic prescriptions such as Gegen Qinlian Formulae and Zuojin Pills can also be used to treat UC. To enrich the traditional Chinese medicine theory, the cognitive theory and perspective of network pharmacology and bioinformatics research of cell signal transduction mechanism of UC are emerging rapidly. Modern pharmacological studies focus on underlying mechanisms for the management of UC with Chinese medicine monomers, single Chinese medicines, and traditional Chinese medicine formulations, alleviating the symptoms of UC, controlling the development of intestinal inflammation, and restoring intestinal function through the regulation of key molecular signaling pathways, including PI3K/Akt, NF-[Formula: see text]B, JAK/STAT, MAPK and Notch. By summarizing current research progressions, this review provides key references for the in-depth exploration of the mechanisms focused on signaling pathways for the clinical management of UC using traditional Chinese medicine.
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Affiliation(s)
- Shihao Zheng
- Graduate School, Hebei University of Traditional Chinese Medicine, Shijiazhuang 050091, P. R. China
| | - Tianyu Xue
- Graduate School, Hebei University of Traditional Chinese Medicine, Shijiazhuang 050091, P. R. China
| | - Bin Wang
- Graduate School, Hebei University of Traditional Chinese Medicine, Shijiazhuang 050091, P. R. China
| | - Haolin Guo
- Graduate School, Hebei University of Traditional Chinese Medicine, Shijiazhuang 050091, P. R. China
| | - Qiquan Liu
- Graduate School, Hebei University of Traditional Chinese Medicine, Shijiazhuang 050091, P. R. China
- Department of Spleen and Stomach, First Affiliated Hospital of Hebei University of Traditional Chinese Medicine, Shijiazhuang 050011, P. R. China
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Lin Y, Liu H, Bu L, Chen C, Ye X. Review of the Effects and Mechanism of Curcumin in the Treatment of Inflammatory Bowel Disease. Front Pharmacol 2022; 13:908077. [PMID: 35795556 PMCID: PMC9250976 DOI: 10.3389/fphar.2022.908077] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 06/02/2022] [Indexed: 11/27/2022] Open
Abstract
Curcumin is extracted from the rhizomes of Curcuma longa L. It is now widely used in food processing, cosmetics, dyes, etc. Current researching indicates that curcumin has high medical value, including anti-inflammatory, antioxidant, anti-tumor, anti-apoptotic, anti-fibrosis, immune regulation and other effects, and can be used to treat a variety of diseases. Inflammatory bowel disease (IBD) is a nonspecific inflammatory disease of the intestine including Crohn’s disease (CD) and ulcerative colitis (UC). The drug treatment effect is often limited and accompanied by side effects. A large number of basic and clinical studies have shown that curcumin has the effect of treating IBD and also can maintain the remission of IBD. In this review, the research of curcumin on IBD in recent years is summarized in order to provide reference for further research and application of curcumin.
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Memarzia A, Saadat S, Behrouz S, Boskabady MH. Curcuma longa and curcumin affect respiratory and allergic disorders, experimental and clinical evidence: A comprehensive and updated review. Biofactors 2022; 48:521-551. [PMID: 34932258 DOI: 10.1002/biof.1818] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 12/05/2021] [Indexed: 01/23/2023]
Abstract
Curcuma longa and its constituents, mainly curcumin, showed various of pharmacological effects in previous studies. This review article provides updated and comprehensive experimental and clinical evidence regarding the effects of C. longa and curcumin on respiratory, allergic, and immunologic disorders. Using appropriate keywords, databases including PubMed, Science Direct, and Scopus were searched until the end of October 2021. C. longa extracts and its constituent, curcumin, showed the relaxant effect on tracheal smooth muscle, which indicates their bronchodilatory effect in obstructive pulmonary diseases. The preventive effects of extracts of C. longa and curcumin were shown in experimental animal models of different respiratory diseases through antioxidant, immunomodulatory, and anti-inflammatory mechanisms. C. longa and curcumin also showed preventive effects on some lung disorders in the clinical studies. It was shown that the effects of C. longa on pulmonary diseases were mainly due to its constituent, curcumin. Pharmacological effects of C. longa extracts and curcumin on respiratory, allergic, and immunologic disorders indicate the possible therapeutic effect of the plant and curcumin on these diseases.
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Affiliation(s)
- Arghavan Memarzia
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Saeideh Saadat
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Sepideh Behrouz
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Hossein Boskabady
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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Heidari Z, Daei M, Boozari M, Jamialahmadi T, Sahebkar A. Curcumin supplementation in pediatric patients: A systematic review of current clinical evidence. Phytother Res 2021; 36:1442-1458. [PMID: 34904764 DOI: 10.1002/ptr.7350] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 11/23/2021] [Accepted: 11/25/2021] [Indexed: 01/01/2023]
Abstract
This systematic review was designed to determine the clinical efficacy and safety of curcumin supplementation for pediatric patients based on clinical trials in children. We systematically searched electronic databases including PubMed, EMBASE, Web of Science, and Scopus for all studies that investigated curcumin administration in the pediatric population without any time frame limitation. Finally, we identified 16 studies for this review. Clinical efficacy and safety of curcumin were assessed in children with inflammatory and immune disorders (including asthma, inflammatory bowel disease (IBD), and juvenile idiopathic arthritis (JIA)), metabolic disorders, autosomal dominant polycystic kidney disease (ADPKD), cystic fibrosis (CF), tetralogy of Fallot (TOF), and infectious diseases. Curcumin was administered in a wide range of doses (45 mg-4,000 mg daily) and durations (2-48 weeks). Overall, curcumin was well tolerated in all studies and improved the severity of inflammatory and immune disorders and metabolic diseases. However, more studies are needed to clarify the role of curcumin supplementation among children with ADPKD, CF, TOF, and infectious diseases. Because of substantial heterogeneity in methodological quality, design, outcomes, dose, duration of intake, formulations, and study populations across studies, no quantitative analysis was performed. Additional large-scale, randomized, placebo-controlled clinical trials are needed to confirm the results of the conducted studies.
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Affiliation(s)
- Zinat Heidari
- Department of Clinical Pharmacy, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Daei
- Department of Clinical Pharmacy, Faculty of Pharmacy, Alborz University of Medical Sciences, Alborz, Iran
| | - Motahareh Boozari
- Department of Pharmacognosy, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Tannaz Jamialahmadi
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,School of Medicine, The University of Western Australia, Perth, Australia.,Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Atabaki M, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohammadi M. Significant immunomodulatory properties of curcumin in patients with osteoarthritis; a successful clinical trial in Iran. Int Immunopharmacol 2020; 85:106607. [DOI: 10.1016/j.intimp.2020.106607] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 05/10/2020] [Accepted: 05/12/2020] [Indexed: 02/07/2023]
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12
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Venkataraman B, Ojha S, Belur PD, Bhongade B, Raj V, Collin PD, Adrian TE, Subramanya SB. Phytochemical drug candidates for the modulation of peroxisome proliferator-activated receptor γ in inflammatory bowel diseases. Phytother Res 2020; 34:1530-1549. [PMID: 32009281 DOI: 10.1002/ptr.6625] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Revised: 12/23/2019] [Accepted: 01/14/2020] [Indexed: 12/12/2022]
Abstract
Plant-based compounds or phytochemicals such as alkaloids, glycosides, flavonoids, volatile oils, tannins, resins, and polyphenols have been used extensively in traditional medicine for centuries and more recently in Western alternative medicine. Extensive evidence suggests that consumption of dietary polyphenolic compounds lowers the risk of inflammatory diseases. The anti-inflammatory properties of several phytochemicals are mediated through ligand-inducible peroxisome proliferator-activated receptors (PPARs), particularly the PPARγ transcription factor. Inflammatory bowel disease (IBD) is represented by ulcerative colitis, which occurs in the mucosa of the colon and rectum, and Crohn's disease (CD) that can involve any segment of gastrointestinal tract. Because of the lack of cost-effective pharmaceutical treatment options, many IBD patients seek and use alternative and unconventional therapies to alleviate their symptoms. PPARγ plays a role in the inhibition of inflammatory cytokine expression and activation of anti-inflammatory immune cells. The phytochemicals reported here are ligands that activate PPARγ, which in turn modulates inflammatory responses. PPARγ is highly expressed in the gut making it a potential therapeutic target for IBDs. This review summarizes the effects of the currently published phytochemicals that modulate the PPARγ pathway and reduce or eliminate colonic inflammation.
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Affiliation(s)
- Balaji Venkataraman
- Department of Physiology, Zayed Bin Sultan Center for Health Sciences, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Shreesh Ojha
- Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Prasanna D Belur
- Department of Chemical Engineering, National Institute of Technology Karnataka, Mangalore, India
| | - Bhoomendra Bhongade
- Department of Pharmaceutical Chemistry, RAK College of Pharmaceutical Sciences, RAK Medical & Health Sciences University, Ras Al Khaimah, United Arab Emirates
| | - Vishnu Raj
- Department of Physiology, Zayed Bin Sultan Center for Health Sciences, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | | | - Thomas E Adrian
- Department of Basic Medical Sciences, Mohamed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Sandeep B Subramanya
- Department of Physiology, Zayed Bin Sultan Center for Health Sciences, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
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Burge K, Gunasekaran A, Eckert J, Chaaban H. Curcumin and Intestinal Inflammatory Diseases: Molecular Mechanisms of Protection. Int J Mol Sci 2019; 20:ijms20081912. [PMID: 31003422 PMCID: PMC6514688 DOI: 10.3390/ijms20081912] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 04/15/2019] [Accepted: 04/17/2019] [Indexed: 02/07/2023] Open
Abstract
Intestinal inflammatory diseases, such as Crohn’s disease, ulcerative colitis, and necrotizing enterocolitis, are becoming increasingly prevalent. While knowledge of the pathogenesis of these related diseases is currently incomplete, each of these conditions is thought to involve a dysfunctional, or overstated, host immunological response to both bacteria and dietary antigens, resulting in unchecked intestinal inflammation and, often, alterations in the intestinal microbiome. This inflammation can result in an impaired intestinal barrier allowing for bacterial translocation, potentially resulting in systemic inflammation and, in severe cases, sepsis. Chronic inflammation of this nature, in the case of inflammatory bowel disease, can even spur cancer growth in the longer-term. Recent research has indicated certain natural products with anti-inflammatory properties, such as curcumin, can help tame the inflammation involved in intestinal inflammatory diseases, thus improving intestinal barrier function, and potentially, clinical outcomes. In this review, we explore the potential therapeutic properties of curcumin on intestinal inflammatory diseases, including its antimicrobial and immunomodulatory properties, as well as its potential to alter the intestinal microbiome. Curcumin may play a significant role in intestinal inflammatory disease treatment in the future, particularly as an adjuvant therapy.
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Affiliation(s)
- Kathryn Burge
- Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, 1200 North Everett Drive, ETNP7504, Oklahoma City, OK 73104, USA.
| | - Aarthi Gunasekaran
- Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, 1200 North Everett Drive, ETNP7504, Oklahoma City, OK 73104, USA.
| | - Jeffrey Eckert
- Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, 1200 North Everett Drive, ETNP7504, Oklahoma City, OK 73104, USA.
| | - Hala Chaaban
- Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, 1200 North Everett Drive, ETNP7504, Oklahoma City, OK 73104, USA.
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El-Naggar ME, Al-Joufi F, Anwar M, Attia MF, El-Bana MA. Curcumin-loaded PLA-PEG copolymer nanoparticles for treatment of liver inflammation in streptozotocin-induced diabetic rats. Colloids Surf B Biointerfaces 2019; 177:389-398. [PMID: 30785036 DOI: 10.1016/j.colsurfb.2019.02.024] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 02/06/2019] [Accepted: 02/11/2019] [Indexed: 12/11/2022]
Abstract
This report focused on loading curcumin (CUR) drug into biodegradable Polylactide-poly(ethylene glycol) (PLA-PEG) copolymer nanoparticles as an effective anti-inflammatory agent in vivo to overcome the limitations resulted from the free CUR. By a simple nano-emulsification technique, hydrophobic CUR was loaded into hydrophobic polymer's segments and stabilized by cationic surfactant. They were then characterized by DLS, TEM, and SEM techniques providing monodispersed and spherical nanoparticles with an average diameter of 117 nm and high surface charge of +35 mV. Thereafter, they were orally administrated into five groups of rats, typically, control (healthy rats), streptozotocin (STZ)-induced diabetic rats, diabetics treated with free CUR, diabetics treated with PLA-PEG NPs, and diabetics treated with CUR-encapsulated PLA-PEG NPs. Next, complete blood analyses were assessed including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and nuclear factor kappa B (NF-ҡB), reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), cyclooxygenase (COX-2), Peroxisome proliferator-activated receptors (PPAR-γ) and transforming growth factor-β1 (TGF-β1). The obtained results demonstrated that diabetes initially produced liver inflammation in rats manifested by leveraging the mean levels of serum AST, ALT inducing oxidative stress resulting in a clear increase in the levels of hepatic MDA and NO concomitant with a remarkable decrease in GSH. Moreover, diabetes significantly increased serum NF-ҡB, hepatic COX-2 and TGF-β1, while highly reduced hepatic PPAR-γ. In contrast, both CUR free and CUR-encapsulated NPs ameliorated the negative changes in diabetes but CUR-encapsulated NPs showed more pronounced treated effect than free CUR. In addition, histopathological investigations were performed on the liver tissues of all groups, showing a mitigation in inflammation while treating with CUR-NPs.
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Affiliation(s)
- Mehrez E El-Naggar
- Department of Pre-Treatment and Finishing of Cellulosic Fabric, Textile Research Division, National Research Centre, Giza, Egypt.
| | - Fakhria Al-Joufi
- Department of Pharmacology, Aljouf University, Sakaka, Saudi Arabia
| | - Mona Anwar
- Research on Children with Special Needs Department, National Research Centre, Giza, Egypt; Department of Basic Sciences and Biomechanics, College of Physical Therapy, Heliopolis University, Cairo, Egypt
| | - Mohamed F Attia
- Department of Pre-Treatment and Finishing of Cellulosic Fabric, Textile Research Division, National Research Centre, Giza, Egypt; Department of Bioengineering, Clemson University, Clemson, SC, 29634, USA.
| | - Mona A El-Bana
- Department of Medical Biochemistry, National Research Centre, Giza, Egypt
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Zhang Z, Li S, Cao H, Shen P, Liu J, Fu Y, Cao Y, Zhang N. The protective role of phloretin against dextran sulfate sodium-induced ulcerative colitis in mice. Food Funct 2019; 10:422-431. [PMID: 30604787 DOI: 10.1039/c8fo01699b] [Citation(s) in RCA: 105] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Phloretin, a dihydrogen chalcone flavonoid, is mainly isolated from apples and strawberries. Phloretin has been proven to have many biological activities such as anti-inflammatory and anti-oxidative. Herein, we investigated the protective efficacy and potential mechanism of phloretin in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. The results showed that phloretin resulted in a reduced DSS-induced disease activity index (DAI), colon length shortening and colonic pathological damage. The levels of pro-inflammatory cytokines in the colon were also decreased by the administration of phloretin. Exploration of the potential mechanism demonstrated that phloretin suppressed the inflammatory response by regulating the nuclear factor-κB (NF-κB), toll-like receptor 4 (TLR4) and peroxisome proliferator-activated receptor γ (PPARγ) pathways. Phloretin also inhibited the DSS-induced (NOD)-like receptor family and pyrin domain containing 3 (NLRP3) inflammasome activations. Further studies found that phloretin reduced key markers of oxidative stress as well as regulated the expression of zonula occludens-1 (ZO-1) and occludin. Interestingly, the concentration of serum lipopolysaccharide (LPS) was significantly decreased. Escherichia coli (E. coli) and Lactobacillus levels were also re-balanced after phloretin treatment. These results indicate that phloretin might be a new dietary strategy for the treatment of UC.
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Affiliation(s)
- Zecai Zhang
- College of Veterinary Medicine, Jilin University, Changchun, China.
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Nuclear Receptors in the Pathogenesis and Management of Inflammatory Bowel Disease. Mediators Inflamm 2019; 2019:2624941. [PMID: 30804707 PMCID: PMC6360586 DOI: 10.1155/2019/2624941] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 12/01/2018] [Accepted: 12/23/2018] [Indexed: 12/12/2022] Open
Abstract
Nuclear receptors (NRs) are ligand-dependent transcription factors that regulate the transcription of target genes. Previous epidemiological and genetic studies have documented the association of NRs with the risk of inflammatory bowel disease (IBD). Although the mechanisms of action of NRs in IBD have not been fully established, accumulating evidence has demonstrated that NRs play complicated roles in regulating intestinal immunity, mucosal barriers, and intestinal flora. As one of the first-line medications for the treatment of IBD, 5-aminosalicylic acid (5-ASA) activates peroxisome proliferator-activated receptor gamma (PPARγ) to attenuate colitis. The protective roles of rifaximin and rifampicin partly depend on promoting pregnane X receptor (PXR) expression. The aims of this review are to discuss the roles of several important NRs, such as PPARγ, PXR, vitamin D receptor (VDR), farnesoid X receptor (FXR), and RAR-related orphan receptor gammat (RORγt), in the pathogenesis of IBD and management strategies based on targeting these receptors.
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Cao H, Liu J, Shen P, Cai J, Han Y, Zhu K, Fu Y, Zhang N, Zhang Z, Cao Y. Protective Effect of Naringin on DSS-Induced Ulcerative Colitis in Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2018; 66:13133-13140. [PMID: 30472831 DOI: 10.1021/acs.jafc.8b03942] [Citation(s) in RCA: 141] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) is an important member of the nuclear receptor superfamily. Previous studies have shown the satisfactory anti-inflammatory role of PPARγ in experimental colitis models, mainly through negatively regulating several transcription factors such as nuclear factor-κB (NF-κB). Therefore, regulating PPARγ and PPARγ-related pathways has great promise for treating ulcerative colitis (UC). In the present study, our objective was to explore the potential effect of naringin on dextran sulfate sodium (DSS) induced UC in mice and its involved potential mechanism. We found that naringin significantly relieved DSS-induced disease activities index (DAI), colon length shortening, and colonic pathological damage. Exploration of the potential mechanisms demonstrated that naringin significantly activated DSS-induced PPARγ and subsequently suppressed NF-κB activation. PPARγ inhibitor GW9662 largely abrogated the roles of naringin in vitro. Moreover, DSS induced the activation of mitogen-activated protein kinase (MAPK) and (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome was inhibited by naringin. Tight junction (TJ) architecture in naringin groups was also maintained by regulating zonula occludens-1 (ZO-1) expression. These results suggested that naringin may be a potential natural agent for protecting mice from DSS-induced UC.
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Affiliation(s)
- Hongyang Cao
- College of Veterinary Medicine , Jilin University , Changchun 130062 , People's Republic of China
| | - Jiuxi Liu
- College of Veterinary Medicine , Jilin University , Changchun 130062 , People's Republic of China
| | - Peng Shen
- College of Veterinary Medicine , Jilin University , Changchun 130062 , People's Republic of China
| | - Jiapei Cai
- College of Veterinary Medicine , Jilin University , Changchun 130062 , People's Republic of China
| | - Yuchang Han
- College of Veterinary Medicine , Jilin University , Changchun 130062 , People's Republic of China
| | - Kunpeng Zhu
- College of Veterinary Medicine , Jilin University , Changchun 130062 , People's Republic of China
| | - Yunhe Fu
- College of Veterinary Medicine , Jilin University , Changchun 130062 , People's Republic of China
| | - Naisheng Zhang
- College of Veterinary Medicine , Jilin University , Changchun 130062 , People's Republic of China
| | - Zecai Zhang
- College of Veterinary Medicine , Jilin University , Changchun 130062 , People's Republic of China
- Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis , Jilin University , Changchun 130062 , People's Republic of China
| | - Yongguo Cao
- College of Veterinary Medicine , Jilin University , Changchun 130062 , People's Republic of China
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18
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Wang Y, Tang Q, Duan P, Yang L. Curcumin as a therapeutic agent for blocking NF-κB activation in ulcerative colitis. Immunopharmacol Immunotoxicol 2018; 40:476-482. [PMID: 30111198 DOI: 10.1080/08923973.2018.1469145] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Ulcerative colitis (UC) is a chronic, relapsing, remitting, and inflammatory disorder that afflicts millions of people around the world. It carries a substantial economic burden, reducing the quality of life, ability to work, and increasing disability. Conventional medical treatment of UC includes the use of aminosalicylates, corticosteroids, and immunosuppressive drugs. However, these medicines are not always effective due to some serious side effects. Nuclear factor-kappa B (NF-κB) is a key factor in the inflammatory setting and strongly affects the course of mucosal inflammation in UC. This review aims to describe the complex role of NF-κB in UC and discuss existing pharmacological attempts by curcumin for blocking NF-κB activation to develop new therapeutic strategies in UC. Several studies have shown intriguing pharmacologic effects associated with curcumin, which inhibits NF-κB expression by regulating NF-κB/IkB pathway and down-regulation expression of pro-inflammatory cytokines, such as Interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α. The efficacy of curcumin has been confirmed in several experimental models of UC. Furthermore, curcumin significantly induced clinical remission in active mild-to-moderate UC patients and reduced clinical relapse in quiescent UC patients. The inhibitory effects of curcumin on NF-κB and its unrivaled safety profile indicate that it remains effective for the treatment of UC. In addition, curcumin is a nontoxic, inexpensive, and easily available natural polyphenol. In conclusion, curcumin can be used as a potential and safe drug in the management of patients with remission and mild-to-moderate UC.
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Affiliation(s)
- Yiqing Wang
- a Department of Gastroenterology , Yancheng First Peoples' Hospital , Yancheng , Jiangsu , China
| | - Qichun Tang
- b Department of Nursing , Yancheng First Peoples' Hospital , Yancheng , Jiangsu , China
| | - Peibei Duan
- c Department of Nursing , Jiangsu Province Hospital of Traditional Chinese Medicine , Nanjing , Jiangsu , China
| | - Lihua Yang
- d Department of Oncology , Jiangsu Province Hospital of Traditional Chinese Medicine , Nanjing , Jiangsu , China
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Heming M, Gran S, Jauch SL, Fischer-Riepe L, Russo A, Klotz L, Hermann S, Schäfers M, Roth J, Barczyk-Kahlert K. Peroxisome Proliferator-Activated Receptor-γ Modulates the Response of Macrophages to Lipopolysaccharide and Glucocorticoids. Front Immunol 2018; 9:893. [PMID: 29867927 PMCID: PMC5949563 DOI: 10.3389/fimmu.2018.00893] [Citation(s) in RCA: 101] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 04/10/2018] [Indexed: 12/22/2022] Open
Abstract
Although glucocorticoids (GC) represent the most frequently used immunosuppressive drugs, their effects are still not well understood. In our previous studies, we have shown that treatment of monocytes with GC does not cause a global suppression of monocytic effector functions, but rather induces differentiation of a specific anti-inflammatory phenotype. The anti-inflammatory role of peroxisome proliferator-activated receptor (PPAR)-γ has been extensively studied during recent years. However, a relationship between GC treatment and PPAR-γ expression in macrophages has not been investigated so far. Studies using PPAR-γ-deficient mice have frequently provided controversial results. A potential reason is the use of primary cells, which commonly represent inhomogeneous populations burdened with side effects and influenced by bystander cells. To overcome this constraint, we established ER-Hoxb8-immortalized bone marrow-derived macrophages from Ppargfl/fl and LysM-Cre Ppargfl/fl mice in this study. In contrast to primary macrophages, the ER-Hoxb8 system allows the generation of a homogeneous and well-defined population of resting macrophages. We could show that the loss of PPAR-γ resulted in delayed kinetic of differentiation of monocytes into macrophages as assessed by reduced F4/80, but increased Ly6C expression in early phases of differentiation. As expected, PPAR-γ-deficient macrophages displayed an increased pro-inflammatory phenotype upon long-term LPS stimulation characterized by an elevated production of pro-inflammatory cytokines TNF-α, IL1-β, IL-6, IL-12 and a reduced production of anti-inflammatory cytokine IL-10 compared to PPAR-γ WT cells. Moreover, PPAR-γ-deficient macrophages showed impaired phagocytosis. GC treatment of macrophages led to the upregulation of PPAR-γ expression. However, there were no differences in GC-induced suppression of cytokines between both cell types, implicating a PPAR-γ-independent mechanism. Intriguingly, GC treatment resulted in an increased in vitro migration only in PPAR-γ-deficient macrophages. Performing a newly developed in vivo cell-tracking experiment, we could confirm that GC induces an increased recruitment of PPAR-γ KO, but not PPAR-γ WT macrophages to the site of inflammation. Our findings suggest a specific effect of PPAR-γ on GC-induced migration in macrophages. In conclusion, we could demonstrate that PPAR-γ exerts anti-inflammatory activities and shapes macrophage functions. Moreover, we identified a molecular link between GC and PPAR-γ and could show for the first time that PPAR-γ modulates GC-induced migration in macrophages.
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Affiliation(s)
- Michael Heming
- Institute of Immunology, University of Muenster, Muenster, Germany.,Department of Neurology, University of Muenster, Muenster, Germany
| | - Sandra Gran
- Institute of Immunology, University of Muenster, Muenster, Germany
| | - Saskia-L Jauch
- Institute of Immunology, University of Muenster, Muenster, Germany
| | | | - Antonella Russo
- Institute of Immunology, University of Muenster, Muenster, Germany
| | - Luisa Klotz
- Department of Neurology, University of Muenster, Muenster, Germany
| | - Sven Hermann
- European Institute for Molecular Imaging, University of Muenster, Muenster, Germany
| | - Michael Schäfers
- European Institute for Molecular Imaging, University of Muenster, Muenster, Germany
| | - Johannes Roth
- Institute of Immunology, University of Muenster, Muenster, Germany
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Zhang M, Zhou L, Zhang S, Yang Y, Xu L, Hua Z, Zou X. Bifidobacterium longum affects the methylation level of forkhead box P3 promoter in 2, 4, 6-trinitrobenzenesulphonic acid induced colitis in rats. Microb Pathog 2017; 110:426-430. [PMID: 28733028 DOI: 10.1016/j.micpath.2017.07.029] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 07/11/2017] [Accepted: 07/17/2017] [Indexed: 01/03/2023]
Abstract
Bifidobacterium longum (B. Longum) is a common probiotic colonized in the human gut and against the development of chronic inflammation including inflammatory bowel disease (IBD). But the underlying mechanism remains unknown. The aim of this study was to evaluate the affection of B. longum on the methylation levels of forkhead box P3 (Foxp3) promoter. 2, 4, 6-trinitrobenzenesulphonic acid (TNBS)-induced colitis rat models were treated with B. longum or medium, respectively. The genomic DNA of spleen peripheral blood mononuclear cells (PBMC) cells was extracted. After bisulphite treatment and pyrosequencing, the methylation levels of each CpG sites in the promoter of forkhead box protein P3 (Foxp3) were analyzed. B. Longum treatment changes the methylation level in Foxp3 promoter in TNBS-treated colitis rats, and significantly demethylates several CpG sites in Foxp3 promoter. The demethylation of Foxp3 promoter might be involved in the effectiveness of B. Longum treatment for IBD. Further research remains necessary to investigate the role of B. Longum in Foxp3 demethylation. Using B. Longum or its metabolic products is an option for further investigations on potential treatments for IBD.
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Affiliation(s)
- Ming Zhang
- Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, China; Jiangsu Clinical Medical Center of Digestive Disease, China
| | - Lixing Zhou
- Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, China; Jiangsu Clinical Medical Center of Digestive Disease, China
| | - Shu Zhang
- Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, China; Jiangsu Clinical Medical Center of Digestive Disease, China
| | - Yang Yang
- Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, China; Jiangsu Clinical Medical Center of Digestive Disease, China
| | - Lei Xu
- Department of Gastroenterology, Nanjing Medical University Affiliated Drum Tower Clinical Medical College, Nanjing 210008, China
| | - Zichun Hua
- The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, China
| | - Xiaoping Zou
- Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, China; Jiangsu Clinical Medical Center of Digestive Disease, China.
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Fu Y, Ma J, Shi X, Song XY, Yang Y, Xiao S, Li J, Gu WJ, Huang Z, Zhang J, Chen J. A novel pyrazole-containing indolizine derivative suppresses NF-κB activation and protects against TNBS-induced colitis via a PPAR-γ-dependent pathway. Biochem Pharmacol 2017; 135:126-138. [DOI: 10.1016/j.bcp.2017.03.013] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Accepted: 03/17/2017] [Indexed: 12/19/2022]
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Currò D, Ianiro G, Pecere S, Bibbò S, Cammarota G. Probiotics, fibre and herbal medicinal products for functional and inflammatory bowel disorders. Br J Pharmacol 2017; 174:1426-1449. [PMID: 27696378 PMCID: PMC5429330 DOI: 10.1111/bph.13632] [Citation(s) in RCA: 109] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Revised: 08/11/2016] [Accepted: 09/13/2016] [Indexed: 12/11/2022] Open
Abstract
Functional bowel disorders (FBD), mainly irritable bowel syndrome (IBS) and functional constipation (FC, also called chronic idiopathic constipation), are very common worldwide. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, although less common, has a strong impact on patients' quality of life, as well as being highly expensive for our healthcare. A definite cure for those disorders is still yet to come. Over the years, several therapeutic approaches complementary or alternative to traditional pharmacological treatments, including probiotics, prebiotics, synbiotics, fibre and herbal medicinal products, have been investigated for the management of both groups of diseases. However, most available studies are biased by several drawbacks, including small samples and poor methodological quality. Probiotics, in particular Saccharomyces boulardii and Lactobacilli (among which Lactobacillus rhamnosus), synbiotics, psyllium, and some herbal medicinal products, primarily peppermint oil, seem to be effective in ameliorating IBS symptoms. Synbiotics and fibre seem to be beneficial in FC patients. The probiotic combination VSL#3 may be effective in inducing remission in patients with mild-to-moderate ulcerative colitis, in whom Escherichia coli Nissle 1917 seems to be as effective as mesalamine in maintaining remission. No definite conclusions can be drawn as to the efficacy of fibre and herbal medicinal products in IBD patients due to the low number of studies and the lack of randomized controlled trials that replicate the results obtained in the individual studies conducted so far. Thus, further, well-designed studies are needed to address the real role of these therapeutic options in the management of both FBD and IBD. LINKED ARTICLES This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.
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Affiliation(s)
- Diego Currò
- Institute of PharmacologySchool of Medicine, Catholic University of the Sacred HeartL.go F. Vito 100168RomeItaly
| | - Gianluca Ianiro
- Department of Internal MedicineSchool of Medicine, Catholic University of the Sacred HeartL.go F. Vito 100168RomeItaly
| | - Silvia Pecere
- Department of Internal MedicineSchool of Medicine, Catholic University of the Sacred HeartL.go F. Vito 100168RomeItaly
| | - Stefano Bibbò
- Department of Clinical and Experimental MedicineUniversity of SassariV.le S. Pietro, 807100SassariItaly
| | - Giovanni Cammarota
- Department of Internal MedicineSchool of Medicine, Catholic University of the Sacred HeartL.go F. Vito 100168RomeItaly
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23
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Abdollahi E, Momtazi AA, Johnston TP, Sahebkar A. Therapeutic effects of curcumin in inflammatory and immune‐mediated diseases: A nature‐made jack‐of‐all‐trades? J Cell Physiol 2017; 233:830-848. [DOI: 10.1002/jcp.25778] [Citation(s) in RCA: 190] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2016] [Accepted: 01/05/2017] [Indexed: 12/14/2022]
Affiliation(s)
- Elham Abdollahi
- Department of Medical ImmunologySchool of Medicine, Mashhad University of Medical SciencesMashhadIran
- Student Research CommitteeMashhad University of Medical SciencesMashhadIran
| | - Amir Abbas Momtazi
- Student Research Committee, Nanotechnology Research Center, Department of Medical BiotechnologySchool of Medicine, Mashhad University of Medical SciencesMashhadIran
| | - Thomas P. Johnston
- Division of Pharmaceutical SciencesSchool of Pharmacy, University of Missouri‐Kansas CityKansas CityMissouri
| | - Amirhossein Sahebkar
- Biotechnology Research CenterMashhad University of Medical SciencesMashhadIran
- Neurogenic Inflammation Research CenterMashhad University of Medical SciencesMashhadIran
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24
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Zhao HM, Han F, Xu R, Huang XY, Cheng SM, Huang MF, Yue HY, Wang X, Zou Y, Xu HL, Liu DY. Therapeutic effect of curcumin on experimental colitis mediated by inhibiting CD8 +CD11c + cells. World J Gastroenterol 2017; 23:1804-1815. [PMID: 28348486 PMCID: PMC5352921 DOI: 10.3748/wjg.v23.i10.1804] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2016] [Revised: 12/25/2016] [Accepted: 01/17/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To verify whether curcumin (Cur) can treat inflammatory bowel disease by regulating CD8+CD11c+ cells.
METHODS We evaluated the suppressive effect of Cur on CD8+CD11c+ cells in spleen and Peyer’s patches (PPs) in colitis induced by trinitrobenzene sulfonic acid. Mice with colitis were treated by 200 mg/kg Cur for 7 d. On day 8, the therapeutic effect of Cur was evaluated by visual assessment and histological examination, while co-stimulatory molecules of CD8+CD11c+ cells in the spleen and PPs were measured by flow cytometry. The levels of interleukin (IL)-10, interferon (IFN)-γ and transforming growth factor (TGF)-β1 in spleen and colonic mucosa were determined by ELISA.
RESULTS The disease activity index, colon weight, weight index of colon and histological score of experimental colitis were obviously decreased after Cur treatment, while the body weight and colon length recovered. After treatment with Cur, CD8+CD11c+ cells were decreased in the spleen and PPs, and the expression of major histocompatibility complex II, CD205, CD40, CD40L and intercellular adhesion molecule-1 was inhibited. IL-10, IFN-γ and TGF-β1 levels were increased compared with those in mice with untreated colitis.
CONCLUSION Cur can effectively treat experimental colitis, which is realized by inhibiting CD8+CD11c+ cells.
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The Anti-Inflammatory and Antioxidant Effects of Curcumin in Middle Ear Infection. J Craniofac Surg 2017; 27:e494-7. [PMID: 27380582 DOI: 10.1097/scs.0000000000002810] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
AIM To investigate and analyze the anti-inflammatory and antioxidant efficacy of curcumin in experimentally induced middle ear infection. METHOD Twenty-four Wistar albino rats with otomicroscopic examination findings within normal limits were included in the study. Study groups were established after Streptococcus pneumoniae was inoculated into the middle ear cavity of all rats. No medication was administered to Group 1, the control group. Group 2 was administered 50 mg/kg/day amoxicillin intraperitoneally. Group 3 was administered 50 mg/kg/day amoxicillin together with 30 mg/kg/day curcumin intraperitoneally. Blood specimens and temporal bones were collected on the 10th day of medication from the 22 rats in which acute otitis media developed. Serum glutathione peroxidase and superoxide dismutase activities and malondialdehyde levels were measured. Inflammatory cell infiltration, vascular proliferation, and epithelial proliferation were assessed histopathologically in middle ear mucosa specimens, and the results were compared among the groups. RESULTS Malondialdehyde levels in the group given curcumin were significantly lower than those of the control group, while serum glutathione peroxidase activity was also lower compared to that of the control group. No significant difference was observed among the groups in terms of superoxide dismutase activity. Although there were no significant findings in terms of histopathological data, epithelial proliferation in the groups receiving antibiotherapy was suppressed compared to the control group. Similarly, curcumin was observed to have a positive effect on inflammatory cell infiltration. No significant changes were observed in terms of vascular proliferation. CONCLUSION With its wide and safe dose range, curcumin represents grounds for optimism in terms of anti-inflammatory treatment in acute otitis media.
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Marion-Letellier R, Savoye G, Ghosh S. IBD: In Food We Trust. J Crohns Colitis 2016; 10:1351-1361. [PMID: 27194533 DOI: 10.1093/ecco-jcc/jjw106] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 05/10/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Both science and patients associate diet with inflammatory bowel disease [IBD]. There is no doubt that links between IBD and diet are numerous, based on both epidemiological studies and experimental studies. However, scientific evidence to support dietary advice is currently lacking, and dietary counselling for IBD patients is often limited in clinical practice to the improvement of nutrient intake. This review aimed to focus on both patient's beliefs about and molecular mechanisms for crosstalk between nutrients and inflammation. METHODS A literature search using PubMed was performed to identify relevant studies on diet and/or nutrients and their role in IBD. Pubmed [from inception to January 20, 2016] was searched using the terms: 'Crohn', 'colitis',' intestinal epithelial cells', and a list of terms relating to diet or numerous specific nutrients. Terms associated with nutrients were individually tested in the context of IBD. Reference lists from studies selected were manually searched to identify further relevant reports. Manuscripts about diet in the context of IBD from basic science, epidemiological studies, or clinical trials were selected and reviewed. Only articles published in English were included. RESULTS Epidemiological studies highlight the key role of diet in IBD development, and many IBD patients report diet as a triggering factor in relapse of disease. In addition, we present research on the impact of nutrients on innate immunity. CONCLUSION Diet may offer an alternative approach to restoring deficient innate immunity in IBD, and this may be the scientific rationale for providing dietary counselling for IBD patients.
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Affiliation(s)
| | - Guillaume Savoye
- INSERM Unit UMR1073, Rouen University and Rouen University Hospital, Rouen cedex, France.,Department of Gastroenterology, Rouen University Hospital, Rouen cedex, France
| | - Subrata Ghosh
- Division of Gastroenterology, University of Calgary, Alberta, Canada
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Luo J, Qu J, Yang R, Ge MX, Mei Y, Zhou BT, Qu Q. Phytochemicals Mediate the Expression and Activity of OCTN2 as Activators of the PPARγ/RXRα Pathway. Front Pharmacol 2016; 7:189. [PMID: 27445823 PMCID: PMC4925669 DOI: 10.3389/fphar.2016.00189] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2016] [Accepted: 06/14/2016] [Indexed: 12/20/2022] Open
Abstract
Many phytochemicals exert activities as agonists of peroxisome proliferator-activated receptor gamma (PPARγ). This study aims to investigate whether phytochemicals are agonists of the PPARγ/RXRα pathway and modulate the target gene OCTN2. In this study, a luciferase reporter gene system was used to screen novel OCTN2 activators from 39 phytochemicals. Kaempferol, curcumin, and puerarin were found to show the significant PPRE-mediated luciferase activities (>150%) at 20 μM and showed a dose-dependent manner. Phytochemicals also elevated the mRNA and protein expression of OCTN2 in a dose-dependent fashion in colorectal cancer SW480 cells. These induction effects were gradually inhibited by PPARγ antagonist GW9662 in the luciferase reporter gene system and in SW480 cells. Moreover, the results of cell viability assay imply that three phytochemicals probably induce OCTN2 expression leading to the enhanced uptake of its substrate, oxaliplatin, thereby making cells more sensitive to oxaliplatin. The molecular docking study showed the possible binding sites of phytochemicals in PPARγ protein, and all of the docked phytochemicals fitted the same active pocket in PPARγ as troglitazone. All three phytochemicals exhibited hydrogen bonds between their polar moieties and the amino acid residues. Thus, we identified three phytochemicals as PPARγ ligands, which potentiated the expression and activity of OCTN2.
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Affiliation(s)
- Jian Luo
- Department of Pharmacy, Xiangya Hospital, Central South University Changsha, China
| | - Jian Qu
- Department of Pharmacy, Second Xiangya Hospital and Institute of Clinical Pharmacy, Central South University Changsha, China
| | - Rui Yang
- Department of Pharmacy, Xiangya Hospital, Central South University Changsha, China
| | - Meng-Xue Ge
- Institute of Clinical Pharmacology, Xiangya Hospital, Central South University Changsha, China
| | - Yin Mei
- Institute of Clinical Pharmacology, Xiangya Hospital, Central South University Changsha, China
| | - Bo-Ting Zhou
- Department of Pharmacy, Xiangya Hospital, Central South University Changsha, China
| | - Qiang Qu
- Department of Pharmacy, Xiangya Hospital, Central South University Changsha, China
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Catalpol reduces the production of inflammatory mediators via PPAR-γ activation in human intestinal Caco-2 cells. J Nat Med 2016; 70:620-6. [DOI: 10.1007/s11418-016-0988-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Accepted: 03/14/2016] [Indexed: 01/08/2023]
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Marion-Letellier R, Savoye G, Ghosh S. Fatty acids, eicosanoids and PPAR gamma. Eur J Pharmacol 2015; 785:44-49. [PMID: 26632493 DOI: 10.1016/j.ejphar.2015.11.004] [Citation(s) in RCA: 219] [Impact Index Per Article: 21.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Revised: 11/02/2015] [Accepted: 11/02/2015] [Indexed: 12/25/2022]
Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) belongs to the family of nuclear nuclear receptors and is mainly expressed in adipose tissue, hematopoietic cells and the large intestine. Contrary to other nuclear receptors that mainly bind a single specific ligand, there are numerous natural PPARγ ligands, in particular fatty acids or their derivatives called eicosanoids. PPARγ have pleiotropic functions: (i) glucose and lipid metabolism regulation, (ii) anti-inflammatory properties, (iii) oxidative stress inhibition, (iv) improvement of endothelial function. Its role has been mainly studied by the use synthetic agonists. In this review, we will focus on the effects of PPARγ mediated through fatty acids and how these have beneficial health properties.
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Affiliation(s)
- Rachel Marion-Letellier
- INSERM Unit UMR1073, Rouen University and Rouen University hospital, 22, boulevard Gambetta, 76183 Rouen cedex, France.
| | - Guillaume Savoye
- INSERM Unit UMR1073, Rouen University and Rouen University hospital, 22, boulevard Gambetta, 76183 Rouen cedex, France; Department of Gastroenterology, Rouen University Hospital, 1 rue de Germont, 76031 Rouen cedex, France
| | - Subrata Ghosh
- Division of Gastroenterology, University of Calgary, Alberta, Canada
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Soubh AA, Abdallah DM, El-Abhar HS. Geraniol ameliorates TNBS-induced colitis: Involvement of Wnt/β-catenin, p38MAPK, NFκB, and PPARγ signaling pathways. Life Sci 2015; 136:142-50. [DOI: 10.1016/j.lfs.2015.07.004] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 06/13/2015] [Accepted: 07/03/2015] [Indexed: 02/07/2023]
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Cho JA, Park E. Curcumin utilizes the anti-inflammatory response pathway to protect the intestine against bacterial invasion. Nutr Res Pract 2015; 9:117-22. [PMID: 25861416 PMCID: PMC4388941 DOI: 10.4162/nrp.2015.9.2.117] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2014] [Revised: 12/23/2014] [Accepted: 12/26/2014] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND/OBJECTIVES Curcumin, a major component of the Curcuma species, contains antioxidant and anti-inflammatory properties. Although it was found to induce apoptosis in cancer cells, the functional role of curcumin as well as its molecular mechanism in anti-inflammatory response, particularly in intestinal cells, has been less investigated. The intestine epithelial barrier is the first barrier and the most important location for the substrate coming from the lumen of the gut. SUBJECTS/METHODS We administered curcumin treatment in the human intestinal epithelial cell lines, T84 and Caco-2. We examined endoplasmic reticulum (ER) stress response by thapsigargin, qPCR of XBP1 and BiP, electrophysiology by wild-type cholera toxin in the cells. RESULTS In this study, we showed that curcumin treatment reduces ER stress and thereby decreases inflammatory response in human intestinal epithelial cells. In addition, curcumin confers protection without damaging the membrane tight junction or actin skeleton change in intestine epithelial cells. Therefore, curcumin treatment protects the gut from bacterial invasion via reduction of ER stress and anti-inflammatory response in intestinal epithelial cells. CONCLUSIONS Taken together, our data demonstrate the important role of curcumin in protecting the intestine by modulating ER stress and inflammatory response post intoxication.
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Affiliation(s)
- Jin Ah Cho
- Division of GI Cell Biology, Boston Children's Hospital, USA
| | - Eunmi Park
- Department of Food and Nutrition, Hannam University, 461-6 Jeonmin-dong, Yuseong-gu, Daejeon 305-811, Korea
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Wang L, Waltenberger B, Pferschy-Wenzig EM, Blunder M, Liu X, Malainer C, Blazevic T, Schwaiger S, Rollinger JM, Heiss EH, Schuster D, Kopp B, Bauer R, Stuppner H, Dirsch VM, Atanasov AG. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review. Biochem Pharmacol 2014; 92:73-89. [PMID: 25083916 PMCID: PMC4212005 DOI: 10.1016/j.bcp.2014.07.018] [Citation(s) in RCA: 437] [Impact Index Per Article: 39.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2014] [Revised: 07/18/2014] [Accepted: 07/21/2014] [Indexed: 12/13/2022]
Abstract
Agonists of the nuclear receptor PPARγ are therapeutically used to combat hyperglycaemia associated with the metabolic syndrome and type 2 diabetes. In spite of being effective in normalization of blood glucose levels, the currently used PPARγ agonists from the thiazolidinedione type have serious side effects, making the discovery of novel ligands highly relevant. Natural products have proven historically to be a promising pool of structures for drug discovery, and a significant research effort has recently been undertaken to explore the PPARγ-activating potential of a wide range of natural products originating from traditionally used medicinal plants or dietary sources. The majority of identified compounds are selective PPARγ modulators (SPPARMs), transactivating the expression of PPARγ-dependent reporter genes as partial agonists. Those natural PPARγ ligands have different binding modes to the receptor in comparison to the full thiazolidinedione agonists, and on some occasions activate in addition PPARα (e.g. genistein, biochanin A, sargaquinoic acid, sargahydroquinoic acid, resveratrol, amorphastilbol) or the PPARγ-dimer partner retinoid X receptor (RXR; e.g. the neolignans magnolol and honokiol). A number of in vivo studies suggest that some of the natural product activators of PPARγ (e.g. honokiol, amorfrutin 1, amorfrutin B, amorphastilbol) improve metabolic parameters in diabetic animal models, partly with reduced side effects in comparison to full thiazolidinedione agonists. The bioactivity pattern as well as the dietary use of several of the identified active compounds and plant extracts warrants future research regarding their therapeutic potential and the possibility to modulate PPARγ activation by dietary interventions or food supplements.
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Affiliation(s)
- Limei Wang
- Department of Pharmacognosy, University of Vienna, Austria
| | - Birgit Waltenberger
- Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Austria
| | | | - Martina Blunder
- Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Austria
| | - Xin Liu
- Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Austria
| | | | - Tina Blazevic
- Department of Pharmacognosy, University of Vienna, Austria
| | - Stefan Schwaiger
- Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Austria
| | - Judith M Rollinger
- Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Austria
| | - Elke H Heiss
- Department of Pharmacognosy, University of Vienna, Austria
| | - Daniela Schuster
- Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Austria
| | - Brigitte Kopp
- Department of Pharmacognosy, University of Vienna, Austria
| | - Rudolf Bauer
- Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Austria
| | - Hermann Stuppner
- Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Austria
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Gilardi D, Fiorino G, Genua M, Allocca M, Danese S. Complementary and alternative medicine in inflammatory bowel diseases: what is the future in the field of herbal medicine? Expert Rev Gastroenterol Hepatol 2014; 8:835-46. [PMID: 24813226 DOI: 10.1586/17474124.2014.917954] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The use of complementary and alternative medicine is wide-spread not only in Eastern countries, but also in the Western world. Despite the increasing evidence on the harmful effects induced by several naturopathic/homeopathic products, patients seem to appreciate these remedies, in particular because they consider them to be absolutely safe. This same phenomenon is common among inflammatory bowel disease (IBD) patients. As a result there is a significant request for scientific data to evaluate both the efficacy and safety of these remedies, and to support the use of such medications as adjuvant treatments to biological and synthetic drugs. We aimed to review the current evidence on efficacy and safety of some natural products that are believed to be effective in inflammatory bowel disease. Further perspectives for the clinical use of herbal products and strategies for improving knowledge about herbal products in IBD are also discussed.
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Affiliation(s)
- Daniela Gilardi
- IBD Center, Gastroenterology, IRCCS Humanitas, Rozzano, Milan, Italy
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Abstract
Curcumin is a polyphenol which is extracted from the plant Curcuma longa. Recent studies showed that curcumin has therapeutic effects on ulcerative colitis. The mechanisms underlying such therapeutic effects on ulcerative colitis include anti-inflammatory, anti-oxidative stress, anti-apoptosis and so on. Curcumin can inhibit the nuclear factor-κB (NF-κB) signaling pathway, mitogen-activated protein kinase (MAPK), signal transducers and activators of transcription-3 (STAT3), and Toll-like receptor 4 (TLR4) signaling pathway, reduce cytokines such as interleukin-23 (IL-23), tumor necrosis factor (TNF)-alpha and interferon gamma, enhance the expression of peroxisome proliferator-activated receptor γ involved in inflammation and immune response regulation, and down-regulate the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), thereby making nitrites returning to basal levels. In this paper, we will review the recent progress in understanding the mechanisms underlying the therapeutic effects of curcumin on ulcerative colitis.
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Telmisartan attenuates colon inflammation, oxidative perturbations and apoptosis in a rat model of experimental inflammatory bowel disease. PLoS One 2014; 9:e97193. [PMID: 24831514 PMCID: PMC4022743 DOI: 10.1371/journal.pone.0097193] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
Accumulating evidence has indicated the implication of angiotensin II in the pathogenesis of inflammatory bowel diseases (IBD) via its proinflammatory features. Telmisartan (TLM) is an angiotensin II receptor antagonist with marked anti-inflammatory and antioxidant actions that mediated its cardio-, reno- and hepatoprotective actions. However, its impact on IBD has not been previously explored. Thus, we aimed to investigate the potential alleviating effects of TLM in tri-nitrobenezene sulphonic acid (TNBS)-induced colitis in rats. Pretreatment with TLM (10 mg/kg p.o.) attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI), colon weight/length ratio, macroscopic damage, histopathological findings and leukocyte migration. TLM suppressed the inflammatory response via attenuation of tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) and myeloperoxidase (MPO) activity as a marker of neutrophil infiltration besides restoration of interleukin-10 (IL-10). TLM also suppressed mRNA and protein expression of nuclear factor kappa B (NF-κB) p65 and mRNA of cyclo-oxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proinflammatory genes with concomitant upregulation of PPAR-γ. The alleviation of TLM to colon injury was also associated with inhibition of oxidative stress as evidenced by suppression of lipid peroxides and nitric oxide (NO) besides boosting glutathione (GSH), total anti-oxidant capacity (TAC) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). With respect to apoptosis, TLM downregulated the increased mRNA, protein expression and activity of caspase-3. It also suppressed the elevation of cytochrome c and Bax mRNA besides the upregulation of Bcl-2. Together, these findings highlight evidences for the beneficial effects of TLM in IBD which are mediated through modulation of colonic inflammation, oxidative stress and apoptosis.
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Baliga MS, Joseph N, Venkataranganna MV, Saxena A, Ponemone V, Fayad R. Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations. Food Funct 2013; 3:1109-17. [PMID: 22833299 DOI: 10.1039/c2fo30097d] [Citation(s) in RCA: 101] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.
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Affiliation(s)
- Manjeshwar Shrinath Baliga
- Department of Research and Development, Father Muller Medical College, Kankanady, Mangalore, Karnataka, India.
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Rosillo MA, Sánchez-Hidalgo M, Cárdeno A, Aparicio-Soto M, Sánchez-Fidalgo S, Villegas I, de la Lastra CA. Dietary supplementation of an ellagic acid-enriched pomegranate extract attenuates chronic colonic inflammation in rats. Pharmacol Res 2012; 66:235-42. [PMID: 22677088 DOI: 10.1016/j.phrs.2012.05.006] [Citation(s) in RCA: 124] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2012] [Revised: 05/16/2012] [Accepted: 05/17/2012] [Indexed: 12/13/2022]
Abstract
Dietary polyphenols present in Punica granatum (pomegranate), such as ellagitannins and ellagic acid (EA) have shown to exert anti-inflammatory and antioxidant properties. This study was designed to evaluate the effects of a dietary EA-enriched pomegranate extract (PE) in a murine chronic model of Cronh's disease (CD). Colonic injury was induced by intracolonic instillation of trinitrobenzensulfonic acid (TNBS). Rats were fed with different diets during 30 days before TNBS instillation and 2 weeks before killing: (i) standard, (ii) PE 250 mg/kg/day, (iii) PE 500 mg/kg/day, (iv) EA 10 mg/kg/day and (v) EA 10 mg/kg/day enriched-PE 250 mg/kg/day. Inflammation response was assessed by histology and MPO activity and TNF-α production. Besides, colonic expressions of iNOS, COX-2, p38, JNK, pERK1/2 MAPKs, IKBα and nuclear p65 NF-κB were studied by western blotting. MPO activity and the TNF-α levels were significantly reduced in dietary fed rats when compared with TNBS group. Similarly, PE and an EA-enriched PE diets drastically decreased COX-2 and iNOS overexpression, reduced MAPKs phosporylation and prevented the nuclear NF-κB translocation. Dietary supplementation of EA contributes in the beneficial effect of PE in this experimental colitis model and may be a novel therapeutic strategy to manage inflammatory bowel disease (IBD).
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Affiliation(s)
- Maria Angeles Rosillo
- Department of Pharmacology, Faculty of Pharmacy, University of Seville. Profesor García González Street 2, 41012 Seville, Spain
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Jungbauer A, Medjakovic S. Anti-inflammatory properties of culinary herbs and spices that ameliorate the effects of metabolic syndrome. Maturitas 2012; 71:227-39. [DOI: 10.1016/j.maturitas.2011.12.009] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2011] [Revised: 12/09/2011] [Accepted: 12/10/2011] [Indexed: 01/07/2023]
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González R, Ballester I, López-Posadas R, Suárez MD, Zarzuelo A, Martínez-Augustin O, Sánchez de Medina F. Effects of flavonoids and other polyphenols on inflammation. Crit Rev Food Sci Nutr 2011; 51:331-62. [PMID: 21432698 DOI: 10.1080/10408390903584094] [Citation(s) in RCA: 369] [Impact Index Per Article: 26.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Flavonoids are a family of polyphenolic compounds which are widespread in nature (vegetables) and are consumed as part of the human diet in significant amounts. There are other types of polyphenols, including, for example, tannins and resveratrol. Flavonoids and related polyphenolic compounds have significant antiinflammatory activity, among others. This short review summarizes the current knowledge on the effects of flavonoids and related polyphenolic compounds on inflammation, with a focus on structural requirements, the mechanisms involved, and pharmacokinetic considerations. Different molecular (cyclooxygenase, lipoxygenase) and cellular targets (macrophages, lymphocytes, epithelial cells, endothelium) have been identified. In addition, many flavonoids display significant antioxidant/radical scavenging properties. There is substantial structural variation in these compounds, which is bound to have an impact on their biological profile, and specifically on their effects on inflammatory conditions. However, in general terms there is substantial consistency in the effects of these compounds despite considerable structural variations. The mechanisms have been studied mainly in myeloid cells, where the predominant effect is an inhibition of NF-κB signaling and the downregulation of the expression of proinflammatory markers. At present there is a gap in knowledge of in vitro and in vivo effects, although the pharmacokinetics of flavonoids has advanced considerably in the last decade. Many flavonoids have been studied for their intestinal antiinflammatory activity which is only logical, since the gastrointestinal tract is naturally exposed to them. However, their potential therapeutic application in inflammation is not restricted to this organ and extends to other sites and conditions, including arthritis, asthma, encephalomyelitis, and atherosclerosis, among others.
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Affiliation(s)
- R González
- Department of Pharmacology, CIBERehd, School of Pharmacy, University of Granada, Granada, Spain
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Goel GA, Kandiel A, Achkar JP, Lashner B. Molecular pathways underlying IBD-associated colorectal neoplasia: therapeutic implications. Am J Gastroenterol 2011; 106:719-30. [PMID: 21386829 DOI: 10.1038/ajg.2011.51] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Chronic inflammatory diseases, depending upon the duration and severity, are frequently associated with an increased risk of developing cancer. A classic paradigm is the enhanced risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD). Carcinogenesis is a multifactorial process that involves accumulation of genetic defects, protein modification, and cell-matrix interaction. In this review, we discuss aspects of chronic inflammation in IBD that influence the development of CRC and highlight the key molecular mediators involved in this process. Also, we identify potential targets that could facilitate earlier detection of dysplasia. The targeted manipulation of specific molecules or pathways could provide opportunities for the development of therapeutic and chemopreventive interventions, which may prove effective in arresting the progression of colitis-associated cancer (CAC), with clinical implications.
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Affiliation(s)
- Gati A Goel
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA.
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Larmonier CB, Midura-Kiela MT, Ramalingam R, Laubitz D, Janikashvili N, Larmonier N, Ghishan FK, Kiela PR. Modulation of neutrophil motility by curcumin: implications for inflammatory bowel disease. Inflamm Bowel Dis 2011; 17:503-15. [PMID: 20629184 PMCID: PMC2958245 DOI: 10.1002/ibd.21391] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Neutrophils (PMN) are the first cells recruited at the site of inflammation. They play a key role in the innate immune response by recognizing, ingesting, and eliminating pathogens and participate in the orientation of the adaptive immune responses. However, in inflammatory bowel disease (IBD) transepithelial neutrophil migration leads to an impaired epithelial barrier function, perpetuation of inflammation, and tissue destruction via oxidative and proteolytic damage. Curcumin (diferulolylmethane) displays a protective role in mouse models of IBD and in human ulcerative colitis, a phenomenon consistently accompanied by a reduced mucosal neutrophil infiltration. METHODS We investigated the effect of curcumin on mouse and human neutrophil polarization and motility in vitro and in vivo. RESULTS Curcumin attenuated lipopolysaccharide (LPS)-stimulated expression and secretion of macrophage inflammatory protein (MIP)-2, interleukin (IL)-1β, keratinocyte chemoattractant (KC), and MIP-1α in colonic epithelial cells (CECs) and in macrophages. Curcumin significantly inhibited PMN chemotaxis against MIP-2, KC, or against conditioned media from LPS-treated macrophages or CEC, a well as the IL-8-mediated chemotaxis of human neutrophils. At nontoxic concentrations, curcumin inhibited random neutrophil migration, suggesting a direct effect on neutrophil chemokinesis. Curcumin-mediated inhibition of PMN motility could be attributed to a downregulation of PI3K activity, AKT phosphorylation, and F-actin polymerization at the leading edge. The inhibitory effect of curcumin on neutrophil motility was further demonstrated in vivo in a model of aseptic peritonitis. CONCLUSIONS Our results indicate that curcumin interferes with colonic inflammation partly through inhibition of the chemokine expression and through direct inhibition of neutrophil chemotaxis and chemokinesis.
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Affiliation(s)
- C B Larmonier
- Department of Pediatrics, Steele Children's Research Center, University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA
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Kundu P, De R, Pal I, Mukhopadhyay AK, Saha DR, Swarnakar S. Curcumin alleviates matrix metalloproteinase-3 and -9 activities during eradication of Helicobacter pylori infection in cultured cells and mice. PLoS One 2011; 6:e16306. [PMID: 21283694 PMCID: PMC3025008 DOI: 10.1371/journal.pone.0016306] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2010] [Accepted: 12/14/2010] [Indexed: 12/12/2022] Open
Abstract
Current therapy-regimens against Helicobacter pylori (Hp) infections have considerable failure rates and adverse side effects that urge the quest for an effective alternative therapy. We have shown that curcumin is capable of eradicating Hp-infection in mice. Here we examine the mechanism by which curcumin protects Hp infection in cultured cells and mice. Since, MMP-3 and -9 are inflammatory molecules associated to the pathogenesis of Hp-infection, we investigated the role of curcumin on inflammatory MMPs as well as proinflammatory molecules. Curcumin dose dependently suppressed MMP-3 and -9 expression in Hp infected human gastric epithelial (AGS) cells. Consistently, Hp-eradication by curcumin-therapy involved significant downregulation of MMP-3 and -9 activities and expression in both cytotoxic associated gene (cag)(+ve) and cag(-ve) Hp-infected mouse gastric tissues. Moreover, we demonstrate that the conventional triple therapy (TT) alleviated MMP-3 and -9 activities less efficiently than curcumin and curcumin's action on MMPs was linked to decreased pro-inflammatory molecules and activator protein-1 activation in Hp-infected gastric tissues. Although both curcumin and TT were associated with MMP-3 and -9 downregulation during Hp-eradication, but unlike TT, curcumin enhanced peroxisome proliferator-activated receptor-γ and inhibitor of kappa B-α. These data indicate that curcumin-mediated healing of Hp-infection involves regulation of MMP-3 and -9 activities.
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Affiliation(s)
- Parag Kundu
- Indian Institute of Chemical Biology, Kolkata, India
| | - Ronita De
- National Institute of Cholera and Enteric Diseases, Kolkata, India
| | - Ipsita Pal
- Indian Institute of Chemical Biology, Kolkata, India
| | | | - Dhira Rani Saha
- National Institute of Cholera and Enteric Diseases, Kolkata, India
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Abstract
Curcumin is a natural product isolated from rhizome of Curcuma longa (turmeric). Extensive research over the past five decades has revealed several important functions of curcumin. Animal studies and clinical trials have suggested that curcumin has antioxidant, anti-inflammatory, anti-tumor and immunoregulatory effects. Ulcerative colitis (UC) is a chronic, idiopathic, relapsing intestinal inflammatory disorder of unknown etiology. In experimental colitis, curcumin mediates anti-inflammatory effects by modulating the release of cytokines, inhibiting nuclear factor-κB (NF-κB) and its upstream signaling pathway, activating peroxisome proliferator-activated receptor γ (PPARγ), and down-regulating the activity of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). At present, although there are studies suggesting that curcumin has therapeutic value for patients with UC, further studies are still needed to evaluate the clinical potential of curcumin in these patients.
Key Words: Curcumin; Ulcerative colitis; Cytokine; Nuclear factor-κB; Peroxisome proliferator-activated receptor γ; Cyclooxygenase-2; Inducible nitric oxide synthase
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44
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Efficacy of a novel sphingosine kinase inhibitor in experimental Crohn’s disease. Inflammopharmacology 2010; 18:73-85. [DOI: 10.1007/s10787-010-0032-x] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2009] [Accepted: 01/20/2010] [Indexed: 12/23/2022]
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Current understanding of the role of PPARγ in gastrointestinal cancers. PPAR Res 2009; 2009:816957. [PMID: 19884989 PMCID: PMC2770108 DOI: 10.1155/2009/816957] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2009] [Accepted: 08/28/2009] [Indexed: 12/19/2022] Open
Abstract
Numerous studies have indicated that PPARγ plays multiple roles such as in inflammation, cell cycle control, cell proliferation, apoptosis, and carcinogenesis, thus PPARγ contributes to the homeostasis. Many in vitro studies have showed that ligand-induced activation of PPARγ possess antitumor effect in many cancers including CRC. However, the role of PPARγ in gastrointestinal cancers, especially in colorectal cancer, is rather controversial. Nevertheless, some recent studies with the positive results on the possible application of PPARγ ligands, such as Bezafibrate or Rosiglitazone in gastrointestinal cancers, have suggested a potential usefulness of PPARγ agonists in cancer prevention and therapy. In this review, the authors discuss the recent developments in the role of PPARγ in gastrointestinal cancers.
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Polyphenols in the prevention and treatment of sepsis syndromes: Rationale and pre-clinical evidence. Nutrition 2009; 25:981-97. [DOI: 10.1016/j.nut.2009.02.010] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2008] [Revised: 02/16/2009] [Accepted: 02/26/2009] [Indexed: 12/17/2022]
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Sánchez-Calvo JM, Villegas I, Sánchez-Fidalgo S, Camacho-Barquero L, Talero E, Motilva V, Alarcón de la Lastra C. Protective effect of curcumin, aCurcuma longaconstituent, in early colonic inflammation in rats. Drug Dev Res 2009. [DOI: 10.1002/ddr.20319] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Chung SW, Kim MK, Chung JH, Kim DH, Choi JS, Anton S, Seo AY, Park KY, Yokozawa T, Rhee SH, Yu BP, Chung HY. Peroxisome proliferator-activated receptor activation by a short-term feeding of zingerone in aged rats. J Med Food 2009; 12:345-50. [PMID: 19459736 PMCID: PMC6469531 DOI: 10.1089/jmf.2007.0660] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2007] [Accepted: 02/17/2008] [Indexed: 11/13/2022] Open
Abstract
Peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptor family, are key regulators of various metabolic pathways related to lipid and glucose metabolism as well as inflammation. We examined the effect of zingerone, a major ingredient of ginger, on PPAR, hepatic nuclear factor-4 (HNF-4), and nuclear factor-kappaB (NF-kappaB) expression in 21-month-old male Sprague-Dawley rats. Two experimental groups receiving doses of either 2 or 8 mg/kg/day zingerone for 10 days were compared with young rats (6 months old) and an age-matched control group. For molecular work, the endothelial cell line YPEN-1 was used. Both the 2 and 8 mg/kg/day dose of zingerone significantly increased DNA binding activities of PPARs (2.8-fold). Expression of HNF-4 was also increased in the group receiving the 8 mg/kg/day dose. We further showed that zingerone partially prevented the age-related decline in PPAR expression. In vitro experiments revealed zingerone (10 microM) increased PPAR expression (2.5-fold) to a similar extent as the PPAR agonist fibrate (5 microM) and suppressed pro-inflammatory transcription factor NF-kappaB activity. Collectively, our findings suggest that zingerone exerts its potent anti-inflammatory action by increasing HNF-4 and PPAR activities, while suppressing NF-kappaB activity.
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Affiliation(s)
| | - Mi Kyung Kim
- Department of Food Science and Nutrition, Pusan National University
| | | | | | - Jae Sue Choi
- Faculty of Food Science and Biotechnology, Pukyong National University, Busan, Republic of Korea
| | - Stephen Anton
- Department of Aging and Geriatrics, College of Medicine, University of Florida, Gainesville, Florida
| | - Arnold Y. Seo
- Department of Aging and Geriatrics, College of Medicine, University of Florida, Gainesville, Florida
| | - Kun-Young Park
- Department of Food Science and Nutrition, Pusan National University
| | - Takako Yokozawa
- Institute of Natural Medicine, Toyama University, Toyama, Japan
| | - Sook Hee Rhee
- Department of Food Science and Nutrition, Pusan National University
| | - Byung Pal Yu
- Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas
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Wang JB, Qi LL, Zheng SD, Wang HZ, Wu TX. Curcumin suppresses PPARδ expression and related genes in HT-29 cells. World J Gastroenterol 2009; 15:1346-52. [PMID: 19294764 PMCID: PMC2658832 DOI: 10.3748/wjg.15.1346] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of curcumin on the expression of peroxisome proliferator-activated receptorδ (PPARδ) and related genes in HT-29 cells.
METHODS: HT-29 cells were treated with curcumin (0-80 &mgr;mol/L) for 24 h. The effects of curcumin on the morphology of HT-29 cells were studied by Hoechst 33342 staining. The activity of caspase-3 was determined using DEVD-pNA as substrate. The levels of peroxisome PPARδ, 14-3-3epsilon and vascular endothelial growth factor (VEGF) in HT-29 cells were determined by Western blotting analysis and their mRNA expression was determined by real-time quantitative RT-PCR.
RESULTS: Treatment with 10-80 &mgr;mol/L curcumin induced typical features of apoptosis and activated the caspase-3 in HT-29 cells. The expression of PPARδ, 14-3-3epsilon and VEGF was reduced and the activity of β-catenin/Tcf-4 signaling was inhibited by curcumin treatment.
CONCLUSION: Curcumin can induce apoptosis of HT-29 cells and down-regulate the expression of PPARδ, 14-3-3epsilon and VEGF in HT-29.
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Rahimi R, Mozaffari S, Abdollahi M. On the use of herbal medicines in management of inflammatory bowel diseases: a systematic review of animal and human studies. Dig Dis Sci 2009; 54:471-480. [PMID: 18618255 DOI: 10.1007/s10620-008-0368-x] [Citation(s) in RCA: 92] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2008] [Accepted: 06/03/2008] [Indexed: 12/15/2022]
Abstract
Because of potential adverse events and lack of effectiveness of standard therapies, the use of complementary and alternative medicines (CAM), particularly of herbal therapies, for inflammatory bowel disease (IBD) is increasing. Results from the use of herbal therapies for managing IBD are promising, and no serious adverse events have been reported from them. Herbal therapies show their benefit in managing IBD by different mechanisms such as immune system regulation, antioxidant activity, inhibition of leukotriene B4, inhibition of nuclear factor-kappa B (NF-kappaB), and antiplatelet activity. In this paper, all reported herbal therapies established in animal IBD models or used for managing human IBD are systematically reviewed and their possible mechanisms of action discussed. Conducting clinical trials with high quality and validity (randomized, double blinded, controlled, on a large number of patients) to obtain more conclusive results about the use of herbal therapies in IBD is recommended.
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Affiliation(s)
- Roja Rahimi
- Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran, P.O. Box 14155-6451, Iran.
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