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Kuang W, Xu J, Xu F, Huang W, Majid M, Shi H, Yuan X, Ruan Y, Hu X. Current study of pathogenetic mechanisms and therapeutics of chronic atrophic gastritis: a comprehensive review. Front Cell Dev Biol 2024; 12:1513426. [PMID: 39720008 PMCID: PMC11666564 DOI: 10.3389/fcell.2024.1513426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 11/25/2024] [Indexed: 12/26/2024] Open
Abstract
Chronic atrophic gastritis (CAG) is a prevalent digestive system disease characterized by atrophy of the gastric mucosa and the disappearance of inherent gastric glands. According to the theory of Correa's cascade, CAG is an important pathological stage in the transformation from normal condition to gastric carcinoma. In recent years, the global incidence of CAG has been increasing due to pathogenic factors, including Helicobacter pylori infection, bile reflux, and the consumption of processed meats. In this review, we comprehensively described the etiology and clinical diagnosis of CAG. We focused on elucidating the regulatory mechanisms and promising therapeutic targets in CAG, with the expectation of providing insights and theoretical support for future research on CAG.
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Affiliation(s)
- Weihong Kuang
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
| | - Jialin Xu
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
| | - Fenting Xu
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
| | - Weizhen Huang
- Cancer Center, The First Huizhou Affiliated Hospital, Guangdong Medical University, Huizhou, China
| | - Muhammad Majid
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
| | - Hui Shi
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
| | - Xia Yuan
- Cancer Center, The First Huizhou Affiliated Hospital, Guangdong Medical University, Huizhou, China
| | - Yongdui Ruan
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
- Cancer Center, The First Huizhou Affiliated Hospital, Guangdong Medical University, Huizhou, China
| | - Xianjing Hu
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
- Department of Acupuncture, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
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Boyanova L, Medeiros J, Yordanov D, Gergova R, Markovska R. Turmeric and curcumin as adjuncts in controlling Helicobacter pylori-associated diseases: a narrative review. Lett Appl Microbiol 2024; 77:ovae049. [PMID: 38794899 DOI: 10.1093/lambio/ovae049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 05/19/2024] [Accepted: 05/23/2024] [Indexed: 05/26/2024]
Abstract
Non-antibiotic adjuncts may improve Helicobacter pylori infection control. Our aim was to emphasize curcumin benefits in controlling H. pylori infection. We discussed publications in English mostly published since 2020 using keyword search. Curcumin is the main bioactive substance in turmeric. Curcumin inhibited H. pylori growth, urease activity, three cag genes, and biofilms through dose- and strain-dependent activities. Curcumin also displayed numerous anticancer activities such as apoptosis induction, anti-inflammatory and anti-angiogenic effects, caspase-3 upregulation, Bax protein enhancement, p53 gene activation, and chemosensitization. Supplementing triple regimens, the agent increased H. pylori eradication success in three Iranian studies. Bioavailability was improved by liposomal preparations, lipid conjugates, electrospray-encapsulation, and nano-complexation with proteins. The agent was safe at doses of 0.5->4 g daily, the most common (in 16% of the users) adverse effect being gastrointestinal upset. Notably, curcumin favorably influences the intestinal microbiota and inhibits Clostridioides difficile. Previous reports showed the inhibitory effect of curcumin on H pylori growth. Curcumin may become an additive in the therapy of H. pylori infection, an adjunct for gastric cancer control, and an agent beneficial to the intestinal microbiota. Further examination is necessary to determine its optimal dosage, synergy with antibiotics, supplementation to various eradication regimens, and prophylactic potential.
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Affiliation(s)
- Lyudmila Boyanova
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria
| | - José Medeiros
- Gastroenterology Clinic, Rua do Carmo, 75-1º AA,, 3000 Coimbra, Portugal
| | - Daniel Yordanov
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria
| | - Raina Gergova
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria
| | - Rumyana Markovska
- Department of Medical Microbiology, Medical University of Sofia, 1431 Sofia, Bulgaria
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Kostelecka K, Bryliński Ł, Komar O, Michalczyk J, Miłosz A, Biłogras J, Woliński F, Forma A, Baj J. An Overview of the Spices Used for the Prevention and Potential Treatment of Gastric Cancer. Cancers (Basel) 2024; 16:1611. [PMID: 38672692 PMCID: PMC11049028 DOI: 10.3390/cancers16081611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 04/15/2024] [Accepted: 04/18/2024] [Indexed: 04/28/2024] Open
Abstract
Gastric cancer (GC) ranks third in terms of cancer-related deaths and is the fifth most commonly diagnosed type of cancer. Its risk factors include Helicobacter pylori infection, Epstein-Barr virus infection, the consumption of broiled and charbroiled animal meats, salt-preserved and smoke-enhanced foods, alcohol drinking, tobacco smoking, exposure to ionizing radiation, and positive family history. The limited effectiveness of conventional therapies and the widespread risk factors of GC encourage the search for new methods of treatment and prevention. In the quest for cheap and commonly available medications, numerous studies focus on herbal medicine, traditional brews, and spices. In this review, we outline the potential use of spices, including turmeric, ginger, garlic, black cumin, chili pepper, saffron, black pepper, rosemary, galangal, coriander, wasabi, cinnamon, oregano, cardamom, fenugreek, caraway, clove, dill, thyme, Piper sarmentosum, basil, as well as the compounds they contain, in the prevention and treatment of GC. We present the potential molecular mechanisms responsible for the effectivity of a given seasoning substance and their impact on GC cells. We discuss their potential effects on proliferation, apoptosis, and migration. For most of the spices discussed, we also outline the unavailability and side effects of their use.
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Affiliation(s)
- Katarzyna Kostelecka
- Department of Anatomy, Medical University of Lublin, ul. Jaczewskiego 4, 20-090 Lublin, Poland; (K.K.); (Ł.B.); (O.K.); (J.M.); (A.M.); (J.B.); (J.B.)
| | - Łukasz Bryliński
- Department of Anatomy, Medical University of Lublin, ul. Jaczewskiego 4, 20-090 Lublin, Poland; (K.K.); (Ł.B.); (O.K.); (J.M.); (A.M.); (J.B.); (J.B.)
| | - Olga Komar
- Department of Anatomy, Medical University of Lublin, ul. Jaczewskiego 4, 20-090 Lublin, Poland; (K.K.); (Ł.B.); (O.K.); (J.M.); (A.M.); (J.B.); (J.B.)
| | - Justyna Michalczyk
- Department of Anatomy, Medical University of Lublin, ul. Jaczewskiego 4, 20-090 Lublin, Poland; (K.K.); (Ł.B.); (O.K.); (J.M.); (A.M.); (J.B.); (J.B.)
| | - Agata Miłosz
- Department of Anatomy, Medical University of Lublin, ul. Jaczewskiego 4, 20-090 Lublin, Poland; (K.K.); (Ł.B.); (O.K.); (J.M.); (A.M.); (J.B.); (J.B.)
| | - Jan Biłogras
- Department of Anatomy, Medical University of Lublin, ul. Jaczewskiego 4, 20-090 Lublin, Poland; (K.K.); (Ł.B.); (O.K.); (J.M.); (A.M.); (J.B.); (J.B.)
| | - Filip Woliński
- Department of Forensic Medicine, Medical University of Lublin, ul. Jaczewskiego 8b, 20-090 Lublin, Poland;
| | - Alicja Forma
- Department of Forensic Medicine, Medical University of Lublin, ul. Jaczewskiego 8b, 20-090 Lublin, Poland;
| | - Jacek Baj
- Department of Anatomy, Medical University of Lublin, ul. Jaczewskiego 4, 20-090 Lublin, Poland; (K.K.); (Ł.B.); (O.K.); (J.M.); (A.M.); (J.B.); (J.B.)
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Pisoschi AM, Iordache F, Stanca L, Cimpeanu C, Furnaris F, Geicu OI, Bilteanu L, Serban AI. Comprehensive and critical view on the anti-inflammatory and immunomodulatory role of natural phenolic antioxidants. Eur J Med Chem 2024; 265:116075. [PMID: 38150963 DOI: 10.1016/j.ejmech.2023.116075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 12/17/2023] [Accepted: 12/18/2023] [Indexed: 12/29/2023]
Abstract
The immune response encompasses innate and adaptive immunity, each with distinct and specific activities. The innate immune system is constituted by phagocytic cells, macrophages, monocytes and neutrophils, the cascade system, and different classes of receptors such as toll-like receptors that are exploited by the innate immune cells. The adaptive immune system is antigen-specific, encompassing memory lymphocytes and the corresponding specific receptors. Inflammation is understood as an activation of different signaling pathways such as toll-like receptors or nuclear factor kappa-light-chain-enhancer of activated B cells, with an increase in nitric oxide, inflammatory cytokines and chemokines. Increased oxidative stress has been identified as main source of chronic inflammation. Phenolic antioxidants modulate the activities of lymphocytes and macrophages by impacting cytokines and nitric oxide release, exerting anti-inflammatory effect. The nuclear-factor kappa-light-chain-enhancer of activated B cells signaling pathway and the mitogen-activated protein kinase pathway are targeted, alongside an increase in nuclear factor erythroid 2-related factor mediated antioxidant response, triggering the activity of antioxidant enzymes. The inhibitive potential on phospholipase A2, cyclooxygenase and lipoxygenase in the arachidonic acid pathway, and the subsequent reduction in prostaglandin and leukotriene generation, reveals the potential of phenolics as inflammation antagonists. The immunomodulative potential encompasses the capacity to interfere with proinflammatory cytokine synthesis and with the expression of the corresponding genes. A diet rich in antioxidants can result in prevention of inflammation-related pathologies. More investigations are necessary to establish the role of these antioxidants in therapy. The appropriate delivery system and the prooxidant effects exhibited at large doses, or in the presence of heavy metal cations should be regarded.
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Affiliation(s)
- Aurelia Magdalena Pisoschi
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania.
| | - Florin Iordache
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania
| | - Loredana Stanca
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania
| | - Carmen Cimpeanu
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Land Reclamation and Environmental Engineering, 59 Marasti Blvd, 011464, Bucharest, Romania
| | - Florin Furnaris
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania
| | - Ovidiu Ionut Geicu
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania; University of Bucharest, Faculty of Biology, Department Biochemistry and Molecular Biology, 91-95 Splaiul Independentei, 050095, Bucharest, Romania
| | - Liviu Bilteanu
- Molecular Nanotechnology Laboratory, National Institute for Research and Development in Microtechnologies, 126A, Erou Iancu Nicolae Street, 077190, Bucharest, Romania
| | - Andreea Iren Serban
- University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, Department Preclinical Sciences, 105 Splaiul Independentei, 050097, Bucharest, Romania; University of Bucharest, Faculty of Biology, Department Biochemistry and Molecular Biology, 91-95 Splaiul Independentei, 050095, Bucharest, Romania
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Chen L, Wei S, He Y, Wang X, He T, Zhang A, Jing M, Li H, Wang R, Zhao Y. Treatment of Chronic Gastritis with Traditional Chinese Medicine: Pharmacological Activities and Mechanisms. Pharmaceuticals (Basel) 2023; 16:1308. [PMID: 37765116 PMCID: PMC10537303 DOI: 10.3390/ph16091308] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 08/14/2023] [Accepted: 08/18/2023] [Indexed: 09/29/2023] Open
Abstract
Chronic gastritis (CG) is a common clinical digestive system disease, which is not easyily cured and is prone to recurrence. Traditional Chinese medicine (TCM) plays a significant role in the treatment of CG and has attracted increasing attention for clinical applications. In recent years, a large number of reports have shown that TCM has good therapeutic effect on CG. The aim of this paper is to investigate the pharmacological activities and mechanism of action of TCM in the treatment of CAG. Therefore, by searching the databases of Pubmed, China National Knowledge Infrastructure, Wanfang, and Baidu academic databases, this paper has summarized the molecular mechanisms of TCM in improving CG. The results show that the improvement of GC by TCM is closely related to a variety of molecular mechanisms, including the inhibition of Helicobacter pylori (Hp) infection, alleviation of oxidative stress, improvement of gastric function, repair of gastric mucosa, inhibition of inflammatory response, and apoptosis. More importantly, IRF8-IFN-γ, IL-4-STAT6, Hedgehog, pERK1/2, MAPK, PI3K-Akt, NF-κB, TNFR-c-Src-ERK1/2-c-Fos, Nrf2/HO-1, and HIF-1α/VEGF signaling pathways are considered as important molecular targets for TCM in the treatment of GC. These important findings will provide a direction and a basis for further exploring the pathogenesis of GC and tapping the potential of TCM in clinical treatment. This review also puts forward a bright prospect for future research of TCM in the treatment of CG.
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Affiliation(s)
- Lisheng Chen
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
- Department of Pharmacy, General Hospital of PLA, Beijing 100039, China
| | - Shizhang Wei
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
| | - Yong He
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
| | - Xin Wang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
| | - Tingting He
- Division of Integrative Medicine, The Fifth Medical Center, General Hospital of PLA, Beijing 100039, China; (T.H.); (A.Z.); (R.W.)
| | - Aozhe Zhang
- Division of Integrative Medicine, The Fifth Medical Center, General Hospital of PLA, Beijing 100039, China; (T.H.); (A.Z.); (R.W.)
| | - Manyi Jing
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
| | - Haotian Li
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
| | - Ruilin Wang
- Division of Integrative Medicine, The Fifth Medical Center, General Hospital of PLA, Beijing 100039, China; (T.H.); (A.Z.); (R.W.)
| | - Yanling Zhao
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
- Department of Pharmacy, General Hospital of PLA, Beijing 100039, China
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Li G, Liu X, Miao Z, Hu N, Zheng X. Preparation of Corn Peptides with Anti-Adhesive Activity and Its Functionality to Alleviate Gastric Injury Induced by Helicobacter pylori Infection In Vivo. Nutrients 2023; 15:3467. [PMID: 37571404 PMCID: PMC10421185 DOI: 10.3390/nu15153467] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 07/28/2023] [Accepted: 08/03/2023] [Indexed: 08/13/2023] Open
Abstract
More than 50% of the world population is infected with Helicobacter pylori (H. pylori), which is classified as group I carcinogen by the WHO. H. pylori surface adhesins specifically recognize gastric mucosal epithelial cells' (GES-1 cells) receptor to complete the adhesion. Blocking the adhesion with an anti-adhesion compound is an effective way to prevent H. pylori infection. The present study found that corn protein hydrolysate, hydrolyzed by Neutral, effectively alleviated gastric injury induced by H. pylori infection through anti-adhesive and anti-inflammatory effects in vitro and in vivo. The hydrolysate inhibited H. pylori adhesion to GES-1 cells significantly, and its anti-adhesive activity was 50.44 ± 0.27% at 4 mg/mL, which indicated that the hydrolysate possessed a similar structure to the GES-1 cells' receptor, and exhibited anti-adhesive activity in binding to H. pylori. In vivo, compared with the H. pylori infection model group, the medium and high dose of the hydrolysate (400-600 mg/kg·bw) significantly decreased (p < 0.05) the amount of H. pylori colonization, pro-inflammatory cytokines (IL-6, IL-1β, TNF-α and MPO), chemokines (KC and MCP-1) as well as key metabolites of NF-κB signaling pathway levels (TLR4, MyD88 and NF-κB), and it increased antioxidant enzyme contents (SOD and GSH-Px) and the mitigation of H. pylori-induced pathological changes in the gastric mucosa. Taken together, these results indicated that the hydrolysate intervention can prevent H. pylori-induced gastric injury by anti-adhesive activity and inhibiting the NF-κB signaling pathway's induction of inflammation. Hence, the corn protein hydrolysate might act as a potential anti-adhesive agent to prevent H. pylori infection.
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Affiliation(s)
- Guanlong Li
- Heilongjiang Provincial Key Laboratory of Corn Deep Processing Theory and Technology, College of Food and Bioengineering, Qiqihar University, Qiqihar 161006, China; (G.L.); (Z.M.); (N.H.)
- College of Food Science, Heilongjiang Bayi Agricultural University, Daqing 163319, China;
| | - Xiaolan Liu
- Heilongjiang Provincial Key Laboratory of Corn Deep Processing Theory and Technology, College of Food and Bioengineering, Qiqihar University, Qiqihar 161006, China; (G.L.); (Z.M.); (N.H.)
| | - Zhengfei Miao
- Heilongjiang Provincial Key Laboratory of Corn Deep Processing Theory and Technology, College of Food and Bioengineering, Qiqihar University, Qiqihar 161006, China; (G.L.); (Z.M.); (N.H.)
| | - Nan Hu
- Heilongjiang Provincial Key Laboratory of Corn Deep Processing Theory and Technology, College of Food and Bioengineering, Qiqihar University, Qiqihar 161006, China; (G.L.); (Z.M.); (N.H.)
| | - Xiqun Zheng
- College of Food Science, Heilongjiang Bayi Agricultural University, Daqing 163319, China;
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Sadeghi M, Dehnavi S, Asadirad A, Xu S, Majeed M, Jamialahmadi T, Johnston TP, Sahebkar A. Curcumin and chemokines: mechanism of action and therapeutic potential in inflammatory diseases. Inflammopharmacology 2023; 31:1069-1093. [PMID: 36997729 PMCID: PMC10062691 DOI: 10.1007/s10787-023-01136-w] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 01/09/2023] [Indexed: 04/01/2023]
Abstract
Chemokines belong to the family of cytokines with chemoattractant properties that regulate chemotaxis and leukocyte migration, as well as the induction of angiogenesis and maintenance of hemostasis. Curcumin, the major component of the Curcuma longa rhizome, has various pharmacological actions, including anti-inflammatory, immune-regulatory, anti-oxidative, and lipid-modifying properties. Chemokines and chemokine receptors are influenced/modulated by curcumin. Thus, the current review focuses on the molecular mechanisms associated with curcumin's effects on chemoattractant cytokines, as well as putting into context the many studies that have reported curcumin-mediated regulatory effects on inflammatory conditions in the organs/systems of the body (e.g., the central nervous system, liver, and cardiovascular system). Curcumin's effects on viral and bacterial infections, cancer, and adverse pregnancy outcomes are also reviewed.
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Affiliation(s)
- Mahvash Sadeghi
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sajad Dehnavi
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Asadirad
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Suowen Xu
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | | | - Tannaz Jamialahmadi
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Thomas P Johnston
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA
| | - 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 Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box, Mashhad, 91779-48564, Iran.
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Liang Z, Xu Y, Zhang Y, Zhang X, Song J, Qian H, Jin J. Anticancer applications of phytochemicals in gastric cancer: Effects and molecular mechanism. Front Pharmacol 2023; 13:1078090. [PMID: 36712679 PMCID: PMC9877357 DOI: 10.3389/fphar.2022.1078090] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 12/28/2022] [Indexed: 01/15/2023] Open
Abstract
Gastric cancer (GC) is the fourth most common malignant cancer and is a life-threatening disease worldwide. Phytochemicals have been shown to be a rational, safe, non-toxic, and very promising approach to the prevention and treatment of cancer. It has been found that phytochemicals have protective effects against GC through inhibiting cell proliferation, inducing apoptosis and autophagy, suppressing cell invasion and migration, anti-angiogenesis, inhibit Helicobacter pylori infection, regulating the microenvironment. In recent years, the role of phytochemicals in the occurrence, development, drug resistance and prognosis of GC has attracted more and more attention. In order to better understand the relationship between phytochemicals and gastric cancer, we briefly summarize the roles and functions of phytochemicals in GC tumorigenesis, development and prognosis. This review will probably help guide the public to prevent the occurrence and development of GC through phytochemicals, and develop functional foods or drugs for the prevention and treatment of gastric cancer.
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Affiliation(s)
- Zhaofeng Liang
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Chang Zhou, China
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Yumeng Xu
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Yue Zhang
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Xinyi Zhang
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jiajia Song
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Hui Qian
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Chang Zhou, China
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jianhua Jin
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Chang Zhou, China
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Wang Q, Yao C, Li Y, Luo L, Xie F, Xiong Q, Feng P. Effect of polyphenol compounds on Helicobacter pylori eradication: a systematic review with meta-analysis. BMJ Open 2023; 13:e062932. [PMID: 36604137 PMCID: PMC9827256 DOI: 10.1136/bmjopen-2022-062932] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
OBJECTIVES Polyphenol compounds are classified as organic compounds with phenolic units exhibiting a variety of biological functions. This meta-analysis aims to assess the efficacy and safety of polyphenol compounds (curcumin, cranberry, garlic, liquorice and broccoli) in eradicating Helicobacter pylori. DESIGN Systematic review and meta-analysis. METHODS Literature searches were conducted on PubMed, Embase, The Cochrane Library, Web of Science, Medline, Chinese National Knowledge Infrastructure database, Chinese Scientific Journal Database and Wan Fang database from inception to January 2022. All randomised controlled trials comparing polyphenol compounds with the placebo or used as an adjunct treatment are included in this meta-analysis.The treatment effect for dichotomous outcomes was assessed using risk ratio (RR), while for continuous outcomes, mean differences both with 95% CIs, were used. Subgroup analyses were carried out for different treatment schemes and polyphenol compound species. RESULTS 12 trials were included in the meta-analysis. The total eradication rate of H.pylori in the polyphenol compounds group was higher than in the group without polyphenol compounds. Statistical significance was also observed (RR 1.19, 95% CI 1.03 to 1.38, p=0.02). The most frequent adverse effects of polyphenol compounds included diarrhoea, headache and vomiting. However, there were no differences regarding side effects between the two groups (RR 1.47, 95% CI 0.83 to 2.58, p=0.18). In subgroup analyses, the H.pylori eradication rate regimens with polyphenols therapy was superior to that of regimens without polyphenols therapy in the polyphenols versus placebo subgroup (RR 4.23, 95% CI 1.38 to 12.95, p=0.01), polyphenols plus triple therapy versus triple therapy subgroup (RR 1.11, 95% CI 1.01 to 1.22, p=0.03). CONCLUSION Polyphenol compounds can improve H.pylori eradication rates. Polyphenol compounds plus standard triple therapy can significantly improve the eradication. However, no evidence of a higher incidence of side effects could be found. PROSPERO REGISTRATION NUMBER CRD42022307477.
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Affiliation(s)
- Qiuxiang Wang
- Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Affiliated hospital of Chengdu university of traditional Chinese medicine, Chengdu, Sichuan, China
- Department of traditional Chinese medicine, The Central Hospital of Guangyuan City, Guangyuan, Sichuan, China
| | - Chengjiao Yao
- Department of Geriatrics, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Yilin Li
- Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Affiliated hospital of Chengdu university of traditional Chinese medicine, Chengdu, Sichuan, China
| | - Lihong Luo
- Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Affiliated hospital of Chengdu university of traditional Chinese medicine, Chengdu, Sichuan, China
| | - Fengjiao Xie
- Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Affiliated hospital of Chengdu university of traditional Chinese medicine, Chengdu, Sichuan, China
| | - Qin Xiong
- Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Affiliated hospital of Chengdu university of traditional Chinese medicine, Chengdu, Sichuan, China
| | - Peimin Feng
- Affiliated hospital of Chengdu university of traditional Chinese medicine, Chengdu, Sichuan, China
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10
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Shome S, Talukdar AD, Upadhyaya H. Antibacterial activity of curcumin and its essential nanoformulations against some clinically important bacterial pathogens: A comprehensive review. Biotechnol Appl Biochem 2022; 69:2357-2386. [PMID: 34826356 DOI: 10.1002/bab.2289] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Accepted: 11/22/2021] [Indexed: 12/27/2022]
Abstract
Multidrug-resistant bacterial infections can kill 700,000 individuals globally each year and is considered among the top 10 global health threats faced by humanity as the arsenal of antibiotics is becoming dry and alternate antibacterial molecule is in demand. Nanoparticles of curcumin exhibit appreciable broad-spectrum antibacterial activity using unique and novel mechanisms and thus the process deserves to be reviewed and further researched to clearly understand the mechanisms. Based on the antibiotic resistance, infection, and virulence potential, a list of clinically important bacteria was prepared after extensive literature survey and all recent reports on the antibacterial activity of curcumin and its nanoformulations as well as their mechanism of antibacterial action have been reviewed. Curcumin, nanocurcumin, and its nanocomposites with improved aqueous solubility and bioavailability are very potential, reliable, safe, and sustainable antibacterial molecule against clinically important bacterial species that uses multitarget mechanism such as inactivation of antioxidant enzyme, reactive oxygen species-mediated cellular damage, and inhibition of acyl-homoserine-lactone synthase necessary for quorum sensing and biofilm formation, thereby bypassing the mechanisms of bacterial antibiotic resistance. Nanoformulations of curcumin can thus be considered as a potential and sustainable antibacterial drug candidate to address the issue of antibiotic resistance.
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Affiliation(s)
- Soumitra Shome
- Ethnobotany and Medicinal Plants Research Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India
| | - Anupam Das Talukdar
- Ethnobotany and Medicinal Plants Research Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India
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11
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Mohammadi A, Khanbabaei H, Zandi F, Ahmadi A, Haftcheshmeh SM, Johnston TP, Sahebkar A. Curcumin: A therapeutic strategy for targeting the Helicobacter pylori-related diseases. Microb Pathog 2022; 166:105552. [DOI: 10.1016/j.micpath.2022.105552] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 04/16/2022] [Accepted: 04/19/2022] [Indexed: 12/12/2022]
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12
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Zhang W, Cui N, Ye J, Yang B, Sun Y, Kuang H. Curcumin's prevention of inflammation-driven early gastric cancer and its molecular mechanism. CHINESE HERBAL MEDICINES 2022; 14:244-253. [PMID: 36117672 PMCID: PMC9476644 DOI: 10.1016/j.chmed.2021.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 10/29/2021] [Accepted: 11/27/2021] [Indexed: 02/07/2023] Open
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13
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Sousa C, Ferreira R, Azevedo NF, Oleastro M, Azeredo J, Figueiredo C, Melo LDR. Helicobacter pylori infection: from standard to alternative treatment strategies. Crit Rev Microbiol 2021; 48:376-396. [PMID: 34569892 DOI: 10.1080/1040841x.2021.1975643] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Helicobacter pylori is the major component of the gastric microbiome of infected individuals and one of the aetiological factors of chronic gastritis, peptic ulcer disease and gastric cancer. The increasing resistance to antibiotics worldwide has made the treatment of H. pylori infection a challenge. As a way to overhaul the efficacy of currently used H. pylori antibiotic-based eradication therapies, alternative treatment strategies are being devised. These include probiotics and prebiotics as adjuvants in H. pylori treatment, antimicrobial peptides as alternatives to antibiotics, photodynamic therapy ingestible devices, microparticles and nanoparticles applied as drug delivery systems, vaccines, natural products, and phage therapy. This review provides an updated synopsis of these emerging H. pylori control strategies and discusses the advantages, hurdles, and challenges associated with their development and implementation. An effective human vaccine would be a major achievement although, until now, projects regarding vaccine development have failed or were discontinued. Numerous natural products have demonstrated anti-H. pylori activity, mostly in vitro, but further clinical studies are needed to fully disclose their role in H. pylori eradication. Finally, phage therapy has the potential to emerge as a valid alternative, but major challenges remain, namely the isolation of more H. pylori strictly virulent bacterio(phages).
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Affiliation(s)
- Cláudia Sousa
- Centre of Biological Engineering, University of Minho, Braga, Portugal
| | - Rute Ferreira
- Centre of Biological Engineering, University of Minho, Braga, Portugal
| | - Nuno F Azevedo
- Faculty of Engineering, LEPABE - Department of Chemical Engineering, University of Porto, Porto, Portugal
| | - Mónica Oleastro
- Department of Infectious Diseases, National Institute of Health Dr Ricardo Jorge, Lisbon, Portugal
| | - Joana Azeredo
- Centre of Biological Engineering, University of Minho, Braga, Portugal
| | - Ceu Figueiredo
- i3S - Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.,Ipatimup - Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.,Faculty of Medicine, Department of Pathology, University of Porto, Porto, Portugal
| | - Luís D R Melo
- Centre of Biological Engineering, University of Minho, Braga, Portugal
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14
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Shetty NP, Prabhakaran M, Srivastava AK. Pleiotropic nature of curcumin in targeting multiple apoptotic-mediated factors and related strategies to treat gastric cancer: A review. Phytother Res 2021; 35:5397-5416. [PMID: 34028111 DOI: 10.1002/ptr.7158] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 04/21/2021] [Accepted: 04/30/2021] [Indexed: 12/24/2022]
Abstract
Gastric cancer (GC) is one of the major reasons for cancer-associated death and exhibits the second-highest mortality rate worldwide. Several advanced approaches have been designed to treat GC; however, these strategies possess many innate complications. In view of this, the upcoming research relying on natural products could result in designing potential anticancer agents with fewer side effects. Curcumin, isolated from the rhizomes of Curcuma longa L. has several medicinal properties like antiinflammatory, antioxidant, antiapoptotic, antitumor, and antimetastatic. Such pleiotropic nature of curcumin impedes the invasion and proliferation of GC by targeting several oncogenic factors like p23, human epidermal factor receptor2 including Helicobacter pylori. The side effect of chemotherapy, that is, chemotherapeutic resistance and radiotherapy could be reduced combination therapy of curcumin. Moreover, the photodynamic therapy of curcumin destroys the cancer cells without affecting normal cells. However, further more potential studies are required to establish the potent efficacy of curcumin in the treatment of GC. The current review details the anticancer activities of curcumin and related strategies which could be employed to treat GC with additional focus on its inhibitory properties against viability, proliferation, and migration of GC cells through cell cycle arrest and stimulation by apoptosis-mediated factors.
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Affiliation(s)
- Nandini P Shetty
- Plant Cell Biotechnology Department, CSIR-Central Food Technological Research Institute, Mysore, 570020, India
| | - Manoj Prabhakaran
- Plant Cell Biotechnology Department, CSIR-Central Food Technological Research Institute, Mysore, 570020, India
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15
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A Systematic Review of the Clinical Use of Curcumin for the Management of Gastrointestinal Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1291:295-326. [PMID: 34331698 DOI: 10.1007/978-3-030-56153-6_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Gastrointestinal (GI) diseases are highly prevalent worldwide, with considerable morbidity and mortality. Curcumin has been used for many years as a plant-derived product for the management of various conditions such as abdominal pain and poor digestion. This systematic review was undertaken with the aim of investigating the effect of curcumin or turmeric supplementation on GI diseases. A comprehensive systematic search was conducted in PubMed, Scopus, Web of Science and Google Scholar up to March 2020 to identify clinical trials assessing the effect of curcumin/turmeric alone or in combination with other herbs or nutrients on GI diseases. Twenty-one studies comprising 1478 GI patients were included in the study. Four out of seven studies showed a beneficial effect of curcumin/turmeric supplementation on irritable bowel syndrome (IBS) and six out of seven showed positive effects of these herbs on ulcerative colitis. Two out of four studies highlighted the potential role of curcumin/turmeric in eradication of H. pylori infection. Both studies conducted on peptic ulcer disease and two out of four studies performed on Crohn's disease demonstrated positive effects of curcumin/turmeric supplementation. One study showed curcumin supplementation had no effect on familial adenomatous polyposis. However, in another study, curcumin had favorable effects on proctosigmoiditis. Nine studies reported some minor adverse effects. The results of this systematic review suggest a beneficial effect of curcumin/turmeric supplementation on the management of GI diseases. More randomized clinical controlled trials are needed to confirm these results.
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16
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Effects of Curcumin and Its Analogues on Infectious Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1291:75-101. [PMID: 34331685 DOI: 10.1007/978-3-030-56153-6_5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Infectious diseases (IDs) are life-threatening illnesses, which result from the spread of pathogenic microorganisms such as bacteria, viruses, fungi, and parasites. IDs are a major challenge for the healthcare systems around the world, leading to a wide variety of clinical manifestations and complications. Despite the capability of frontline-approved medications to partially prevent or mitigate the invasion and subsequent damage of IDs to host tissues and cells, problems such as drug resistance, insufficient efficacy, unpleasant side effects, and high expenses stand in the way of their beneficial applications. One strategy is to evaluate currently explored and available bioactive compounds as possible anti-microbial agents. The natural polyphenol curcumin has been postulated to possess various properties including anti-microbial activities. Studies have shown that it possess pleiotropic effects against bacterial- and parasitic-associating IDs including drug-resistant strains. Curcumin can also potentiate the efficacy of available anti-bacterial and anti-parasitic drugs in a synergistic fashion. In this review, we summarize the findings of these studies along with reported controversies of native curcumin and its analogues, alone and in combination, toward its application in future studies as a natural anti-bacterial and anti-parasitic agent.
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17
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Panahi Y, Karbasi A, Valizadegan G, Ostadzadeh N, Soflaei SS, Jamialahmadi T, Majeed M, Sahebkar A. Effect of Curcumin on Severity of Functional Dyspepsia: a Triple Blinded Clinical Trial. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1308:119-126. [PMID: 33861441 DOI: 10.1007/978-3-030-64872-5_10] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BackgroundFunctional dyspepsia is the main cause of upper abdominal discomfort affecting 5-10% of the world population. Despite various therapeutic approaches, up to 50% of patients with functional dyspepsia seek alternative treatments. In the present study we evaluated the effect of curcumin supplementation along with famotidine therapy on severity of functional dyspepsia. A total of 75 patients with functional dyspepsia according to Rome III criteria were allocated into intervention (N = 39) or control (N = 36) groups. The intervention group was treated with a combination of 500 mg curcumin and 40 mg famotidine daily for 1 month. The control group received placebo and 40 mg famotidine. Severity of dyspepsia symptoms was determined using the Hong Kong questionnaire at baseline, after the 1 month treatment and after a 1 month follow-up. The presence of H. pylori antigens in the stool samples was also investigated in all subjects. No significant difference was observed between intervention and control groups in biochemical indices, severity of dyspepsia and rate of H. pylori infection. A significant decrease was observed in severity of dyspepsia (p < 0.001) and rate of H. pylori infection (p = 0.004) immediately after the treatment and follow-up in the curcumin intervention group. This study indicated that curcumin therapy could be a favorable supplementation in the symptom management of functional dyspepsia. Moreover, curcumin could help efficient eradication of H. pylori in these patients.
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Affiliation(s)
- Yunes Panahi
- Pharmacotherapy Department, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Ashraf Karbasi
- Gastroenterology and Hepatology Department, Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Ghasem Valizadegan
- Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | | | | | - Tannaz Jamialahmadi
- Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran
- 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 Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
- Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.
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18
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Ausili A, Gómez-Murcia V, Candel AM, Beltrán A, Torrecillas A, He L, Jiang Y, Zhang S, Teruel JA, Gómez-Fernández JC. A comparison of the location in membranes of curcumin and curcumin-derived bivalent compounds with potential neuroprotective capacity for Alzheimer's disease. Colloids Surf B Biointerfaces 2020; 199:111525. [PMID: 33373844 DOI: 10.1016/j.colsurfb.2020.111525] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 10/14/2020] [Accepted: 12/07/2020] [Indexed: 11/30/2022]
Abstract
Curcumin and two bivalent compounds, namely 17MD and 21MO, both obtained by conjugation of curcumin with a steroid molecule that acts as a membrane anchor, were comparatively studied. When incorporated into 1,2-dipalmitoyl-sn-glycero-3-phosphocholine the compounds showed a very limited solubility in the model membranes. Curcumin and the two bivalent compounds were also incorporated in membranes of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and quenching the fluorescence of pure curcumin or of the curcumin moiety in the bivalent compounds by acrylamide it was seen that curcumin was accessible to this water soluble quencher but the molecule was somehow located in a hydrophobic environment. This was confirmed by quenching with doxyl-phosphatidylcholines, indicating that the curcumin moieties of 17MD and 21MO were in a more polar environment than pure curcumin itself. 1H NOESY MAS-NMR analysis supports this notion by showing that the orientation of curcumin was parallel to the plane of the membrane surface close to C2 and C3 of the fatty acyl chains, while the curcumin moiety of 17MD and 21MO positioned close to the polar part of the membrane with the steroid moiety in the centre of the membrane. Molecular dynamics studies were in close agreement with the experimental results with respect to the likely proximity of the protons studied by NMR and show that 17MD and 21MO have a clear tendency to aggregate in a fluid membrane. The anchorage of the bivalent compounds to the membrane leaving the curcumin moiety near the polar part may be very important to facilitate the bioactivity of the curcumin moiety when used as anti-Alzheimer drugs.
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Affiliation(s)
- Alessio Ausili
- Departamento De Bioquímica y Biología Molecular "A", Facultad de Veterinaria, Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, Apartado de Correos 4021, Murcia, E-30080, Spain
| | - Victoria Gómez-Murcia
- Departamento de Farmacología, Facultad de Medicina, IMIB, Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, Apartado de Correos 4021, Murcia, E-30080, Spain
| | - Adela M Candel
- Departamento De Bioquímica y Biología Molecular "A", Facultad de Veterinaria, Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, Apartado de Correos 4021, Murcia, E-30080, Spain
| | - Andrea Beltrán
- Departamento De Bioquímica y Biología Molecular "A", Facultad de Veterinaria, Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, Apartado de Correos 4021, Murcia, E-30080, Spain
| | - Alejandro Torrecillas
- Departamento De Bioquímica y Biología Molecular "A", Facultad de Veterinaria, Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, Apartado de Correos 4021, Murcia, E-30080, Spain
| | - Liu He
- Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, 23298, United States
| | - Yuqi Jiang
- Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, 23298, United States
| | - Shijun Zhang
- Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, 23298, United States
| | - José A Teruel
- Departamento De Bioquímica y Biología Molecular "A", Facultad de Veterinaria, Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, Apartado de Correos 4021, Murcia, E-30080, Spain
| | - Juan C Gómez-Fernández
- Departamento De Bioquímica y Biología Molecular "A", Facultad de Veterinaria, Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, Apartado de Correos 4021, Murcia, E-30080, Spain.
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Jakubczyk K, Drużga A, Katarzyna J, Skonieczna-Żydecka K. Antioxidant Potential of Curcumin-A Meta-Analysis of Randomized Clinical Trials. Antioxidants (Basel) 2020; 9:antiox9111092. [PMID: 33172016 PMCID: PMC7694612 DOI: 10.3390/antiox9111092] [Citation(s) in RCA: 126] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 11/02/2020] [Accepted: 11/04/2020] [Indexed: 01/15/2023] Open
Abstract
Background: Antioxidant potential is defined as the ability to neutralize oxygen free radicals that are generated in excess due to environmental influences. The body’s defense mechanisms often require support in preventing the effects of oxidative stress. The literature data suggest that curcumin has antioxidant activity that can significantly reduce oxidative stress levels. The aim was to assess the impact of curcumin on oxidative stress markers. Methods: PubMed and Embase were searched from database inception until 27 September 2019 for randomized clinical trials in >20 patients treated with curcumin supplements and randomized to placebo/no intervention/physical activity to verify the antioxidant potential of curcumin. Results: Four studies were included in the meta-analysis, three of which were double-blind and one single-blind. A total of 308 participants took part in the research. A total of 40% of the respondents were men. The average age of participants was 27.60 ± 3.79 years. The average supplementation time was 67 days and the average dose of curcumin administered was 645 mg/24 h. Curcumin significantly increased total antioxidant capacity (TAC) (SMD = 2.696, Z = 2.003, CI = 95%, p = 0.045) and had a tendency to decrease malondialdehyde (MDA) concentration (SMD = −1.579, Z = −1.714, CI = 95%, p = 0.086). Conclusions: Pure curcumin has the potential to reduce MDA concentration and increase total antioxidant capacity.
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Dai C, Wang Y, Sharma G, Shen J, Velkov T, Xiao X. Polymyxins-Curcumin Combination Antimicrobial Therapy: Safety Implications and Efficacy for Infection Treatment. Antioxidants (Basel) 2020; 9:antiox9060506. [PMID: 32526966 PMCID: PMC7346118 DOI: 10.3390/antiox9060506] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 05/31/2020] [Accepted: 06/03/2020] [Indexed: 02/07/2023] Open
Abstract
The emergence of antimicrobial resistance in Gram-negative bacteria poses a huge health challenge. The therapeutic use of polymyxins (i.e., colistin and polymyxin B) is commonplace due to high efficacy and limiting treatment options for multidrug-resistant Gram-negative bacterial infections. Nephrotoxicity and neurotoxicity are the major dose-limiting factors that limit the therapeutic window of polymyxins; nephrotoxicity is a complication in up to ~60% of patients. The emergence of polymyxin-resistant strains or polymyxin heteroresistance is also a limiting factor. These caveats have catalyzed the search for polymyxin combinations that synergistically kill polymyxin-susceptible and resistant organisms and/or minimize the unwanted side effects. Curcumin—an FDA-approved natural product—exerts many pharmacological activities. Recent studies showed that polymyxins–curcumin combinations showed a synergistically inhibitory effect on the growth of bacteria (e.g., Gram-positive and Gram-negative bacteria) in vitro. Moreover, curcumin co-administration ameliorated colistin-induced nephrotoxicity and neurotoxicity by inhibiting oxidative stress, mitochondrial dysfunction, inflammation and apoptosis. In this review, we summarize the current knowledge-base of polymyxins–curcumin combination therapy and discuss the underlying mechanisms. For the clinical translation of this combination to become a reality, further research is required to develop novel polymyxins–curcumin formulations with optimized pharmacokinetics and dosage regimens.
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Affiliation(s)
- Chongshan Dai
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, China; (Y.W.); (J.S.)
- Correspondence: (C.D.); (X.X.); Tel.: +86-156-5282-6026 (C.D.); +86-010-6273-3377 (X.X.)
| | - Yang Wang
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, China; (Y.W.); (J.S.)
| | - Gaurav Sharma
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;
| | - Jianzhong Shen
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, China; (Y.W.); (J.S.)
| | - Tony Velkov
- Department of Pharmacology & Therapeutics, Faculty of Medicine, School of Biomedical Sciences, Dentistry and Health Sciences, the University of Melbourne, Parkville 3052, Australia;
| | - Xilong Xiao
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, China; (Y.W.); (J.S.)
- Correspondence: (C.D.); (X.X.); Tel.: +86-156-5282-6026 (C.D.); +86-010-6273-3377 (X.X.)
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Screening and Identification of Molecular Targets Involved in Preventing Gastric Precancerous Lesions in Chronic Atrophic Gastritis by Qilianshupi Decoction. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2019:5804710. [PMID: 31929816 PMCID: PMC6942842 DOI: 10.1155/2019/5804710] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 07/22/2019] [Accepted: 10/11/2019] [Indexed: 01/22/2023]
Abstract
Chronic atrophic gastritis (CAG) is a common and possibly precancerous digestive tract disease. Development of drugs with effect of preventing precancerous lesions draws the eyes of global researchers. Qilianshupi decoction (QLSP) is a Traditional Chinese Medicine (TCM) that is commonly used to treat CAG, but few studies have explored the mechanism of QLSP on treating CAG. This study investigated the molecular targets of the component herbs of QLSP in preventing precancerous lesions based on network pharmacology. Network pharmacology analysis revealed that the 6 herbs regulated multiple CAG-related genes, among which the most important were cancer-related pathway (apoptosis, p53, and VEGF) and epithelial cell signaling in Helicobacter pylori infection. Further animal experiments showed that the expression of survivin and p53 in precancerous lesions of CAG rats was significantly increased which was suppressed by QLSP. Moreover, telomerase activity was inhibited in precancerous lesions of CAG rats, and telomere length of gastric mucosa was increased, which was reversed by QLSP. Our results suggest that the components of QLSP prevents gastric precancerous lesions through decreasing the expression of survivin and p53 and regulating telomerase activity and telomere length in CAG.
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Teixeira JP, de Castro AA, Soares FV, da Cunha EFF, Ramalho TC. Future Therapeutic Perspectives into the Alzheimer's Disease Targeting the Oxidative Stress Hypothesis. Molecules 2019; 24:E4410. [PMID: 31816853 PMCID: PMC6930470 DOI: 10.3390/molecules24234410] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 11/27/2019] [Accepted: 11/30/2019] [Indexed: 01/12/2023] Open
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease that is usually accompanied by aging, increasingly being the most common cause of dementia in the elderly. This disorder is characterized by the accumulation of beta amyloid plaques (Aβ) resulting from impaired amyloid precursor protein (APP) metabolism, together with the formation of neurofibrillary tangles and tau protein hyperphosphorylation. The exacerbated production of reactive oxygen species (ROS) triggers the process called oxidative stress, which increases neuronal cell abnormalities, most often followed by apoptosis, leading to cognitive dysfunction and dementia. In this context, the development of new therapies for the AD treatment is necessary. Antioxidants, for instance, are promising species for prevention and treatment because they are capable of disrupting the radical chain reaction, reducing the production of ROS. These species have also proven to be adjunctive to conventional treatments making them more effective. In this sense, several recently published works have focused their attention on oxidative stress and antioxidant species. Therefore, this review seeks to show the most relevant findings of these studies.
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Affiliation(s)
- Jéssika P. Teixeira
- Department of Chemistry, Federal University of Lavras, 37200-000 Lavras, Minas Gerais, Brazil; (J.P.T.); (A.A.d.C.); (F.V.S.); (E.F.F.d.C.)
| | - Alexandre A. de Castro
- Department of Chemistry, Federal University of Lavras, 37200-000 Lavras, Minas Gerais, Brazil; (J.P.T.); (A.A.d.C.); (F.V.S.); (E.F.F.d.C.)
| | - Flávia V. Soares
- Department of Chemistry, Federal University of Lavras, 37200-000 Lavras, Minas Gerais, Brazil; (J.P.T.); (A.A.d.C.); (F.V.S.); (E.F.F.d.C.)
| | - Elaine F. F. da Cunha
- Department of Chemistry, Federal University of Lavras, 37200-000 Lavras, Minas Gerais, Brazil; (J.P.T.); (A.A.d.C.); (F.V.S.); (E.F.F.d.C.)
| | - Teodorico C. Ramalho
- Department of Chemistry, Federal University of Lavras, 37200-000 Lavras, Minas Gerais, Brazil; (J.P.T.); (A.A.d.C.); (F.V.S.); (E.F.F.d.C.)
- Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, 500 03 Hradec Kralove, Czech Republic
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Yu Y, Sun J, Wang R, Liu J, Wang P, Wang C. Curcumin Management of Myocardial Fibrosis and its Mechanisms of Action: A Review. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2019; 47:1675-1710. [PMID: 31786946 DOI: 10.1142/s0192415x19500861] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Myocardial fibrosis is implicated as a leading risk factor for heart failure, arrhythmia, and sudden death after cardiac injury, as the excessive interstitial extracellular matrix impedes heart contraction and electrical conduction. Complicated mechanisms involving oxidative stress, pro-inflammatory cytokines, chemokine families, NLRP3 inflammasomes, growth factors, and non-coding RNAs participate in cardiac fibrogenesis and make it difficult to designate specific and effective therapies. Oriental herbs have been popular for thousands of years in the health care of Asian residents, due to their multi-targeted, multi-faceted approaches and their multi-functional effects in fighting difficult and complicated diseases, including cardiovascular disorders such as myocardial fibrosis. Curcumin, a natural polyphenol and yellow pigment obtained from the spice turmeric, was found to have strong anti-oxidant and anti-inflammatory properties. Increasing evidence has shown that curcumin can be used to prevent and treat myocardial fibrosis, when the myocardium suffers pathological pro-fibrotic changes in vivo and in vitro. The present review focuses on recent studies elucidating the mechanisms of curcumin in treating different pathologic conditions, including ischemia, hypoxia/reoxygenation, pressure or volume overload, and hyperglycemia or high-fat-induced cardiac fibrosis. Novel analogs such as C66, B2BrBC, Y20, and J17 have been designed to maximize the therapeutic potentials of curcumin. These optimized curcumin analogs with improved bioavailability and pharmacokinetic profiles need to be clinically verified before curcumin could be recommended for the treatment of myocardial fibrosis.
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Affiliation(s)
- Yonghui Yu
- Department of Traditional Chinese Medicine, China-Japan Friendship Hospital, Beijing 100029, P. R. China
| | - Jinghui Sun
- Graduate School of China Academy of Chinese Medical Science, Beijing 100700, P. R. China
| | - Ru Wang
- Graduate School of China Academy of Chinese Medical Science, Beijing 100700, P. R. China
| | - Jiangang Liu
- Center for Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing 100091, P. R. China
| | - Peili Wang
- Center for Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing 100091, P. R. China
| | - Chenglong Wang
- Center for Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing 100091, P. R. China
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Lobo de Sá FD, Butkevych E, Nattramilarasu PK, Fromm A, Mousavi S, Moos V, Golz JC, Stingl K, Kittler S, Seinige D, Kehrenberg C, Heimesaat MM, Bereswill S, Schulzke JD, Bücker R. Curcumin Mitigates Immune-Induced Epithelial Barrier Dysfunction by Campylobacter jejuni. Int J Mol Sci 2019; 20:ijms20194830. [PMID: 31569415 PMCID: PMC6802366 DOI: 10.3390/ijms20194830] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 09/19/2019] [Accepted: 09/26/2019] [Indexed: 12/26/2022] Open
Abstract
Campylobacter jejuni (C. jejuni) is the most common cause of foodborne gastroenteritis worldwide. The bacteria induce diarrhea and inflammation by invading the intestinal epithelium. Curcumin is a natural polyphenol from turmeric rhizome of Curcuma longa, a medical plant, and is commonly used in curry powder. The aim of this study was the investigation of the protective effects of curcumin against immune-induced epithelial barrier dysfunction in C. jejuni infection. The indirect C. jejuni-induced barrier defects and its protection by curcumin were analyzed in co-cultures with HT-29/B6-GR/MR epithelial cells together with differentiated THP-1 immune cells. Electrophysiological measurements revealed a reduction in transepithelial electrical resistance (TER) in infected co-cultures. An increase in fluorescein (332 Da) permeability in co-cultures as well as in the germ-free IL-10−/− mouse model after C. jejuni infection was shown. Curcumin treatment attenuated the C. jejuni-induced increase in fluorescein permeability in both models. Moreover, apoptosis induction, tight junction redistribution, and an increased inflammatory response—represented by TNF-α, IL-1β, and IL-6 secretion—was observed in co-cultures after infection and reversed by curcumin. In conclusion, curcumin protects against indirect C. jejuni-triggered immune-induced barrier defects and might be a therapeutic and protective agent in patients.
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Affiliation(s)
- Fábia Daniela Lobo de Sá
- Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology, Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany.
| | - Eduard Butkevych
- Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology, Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany.
| | - Praveen Kumar Nattramilarasu
- Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology, Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany.
| | - Anja Fromm
- Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology, Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany.
| | - Soraya Mousavi
- Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 14195 Berlin, Germany.
| | - Verena Moos
- Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany.
| | - Julia C Golz
- German Federal Institute for Risk Assessment (BfR), Department of Biological Safety, National Reference Laboratory for Campylobacter, 12277 Berlin, Germany.
| | - Kerstin Stingl
- German Federal Institute for Risk Assessment (BfR), Department of Biological Safety, National Reference Laboratory for Campylobacter, 12277 Berlin, Germany.
| | - Sophie Kittler
- University of Veterinary Medicine Hannover, Research Center for Emerging Infections and Zoonoses, 30559 Hannover, Germany.
| | - Diana Seinige
- University of Veterinary Medicine Hannover, Research Center for Emerging Infections and Zoonoses, 30559 Hannover, Germany.
| | - Corinna Kehrenberg
- Institute for Veterinary Food Science, Justus-Liebig-University, 35392 Giessen, Germany.
| | - Markus M Heimesaat
- Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 14195 Berlin, Germany.
| | - Stefan Bereswill
- Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 14195 Berlin, Germany.
| | - Jörg-Dieter Schulzke
- Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology, Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany.
| | - Roland Bücker
- Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology, Rheumatology, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany.
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Therapeutic effects of turmeric in several diseases: An overview. Chem Biol Interact 2019; 310:108729. [PMID: 31255636 DOI: 10.1016/j.cbi.2019.108729] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 06/17/2019] [Accepted: 06/26/2019] [Indexed: 02/06/2023]
Abstract
A nutraceutical product can be defined as a substance that has a physiological benefit or provides protection against chronic diseases. The term nutraceutical is a hybrid term derived from the union of "nutrition" and "pharmaceutical". The list of studied nutraceuticals is constantly changing and reflects ongoing market developments, research and consumer interest. Spices, in addition to giving color and taste to foods, are also important nutraceutical. Spices have been an integral part of human diets and commerce for millennia but recently, the recognition of the link between health and nutrition has strengthened their importance in the food sector and sparked the interest of researchers who increasingly engage in trying to determine the mechanisms of action of spices and the countless beneficial properties attributed to them. Among the many existing spices, turmeric is one of the most studied for its antioxidant, anti-inflammatory, antibacterial and anticancer properties. The purpose of this review is to briefly summarize the fundamental characteristics of turmeric and give an overview of the use of this spice in several diseases.
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Patel SS, Acharya A, Ray RS, Agrawal R, Raghuwanshi R, Jain P. Cellular and molecular mechanisms of curcumin in prevention and treatment of disease. Crit Rev Food Sci Nutr 2019; 60:887-939. [PMID: 30632782 DOI: 10.1080/10408398.2018.1552244] [Citation(s) in RCA: 263] [Impact Index Per Article: 43.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Curcumin is a naturally occurring polyphenolic compound present in rhizome of Curcuma longa belonging to the family zingiberaceae. Growing experimental evidence revealed that curcumin exhibit multitarget biological implications signifying its crucial role in health and disease. The current review highlights the recent progress and mechanisms underlying the wide range of pharmacological effects of curcumin against numerous diseases like neuronal, cardiovascular, metabolic, kidney, endocrine, skin, respiratory, infectious, gastrointestinal diseases and cancer. The ability of curcumin to modulate the functions of multiple signal transductions are linked with attenuation of acute and chronic diseases. Numerous preclinical and clinical studies have revealed that curcumin modulates several molecules in cell signal transduction pathway including PI3K, Akt, mTOR, ERK5, AP-1, TGF-β, Wnt, β-catenin, Shh, PAK1, Rac1, STAT3, PPARγ, EBPα, NLRP3 inflammasome, p38MAPK, Nrf2, Notch-1, AMPK, TLR-4 and MyD-88. Curcumin has a potential to prevent and/or manage various diseases due to its anti-inflammatory, anti-oxidant and anti-apoptotic properties with an excellent safety profile. In contrast, the anti-cancer effects of curcumin are reflected due to induction of growth arrest and apoptosis in various premalignant and malignant cells. This review also carefully emphasized the pharmacokinetics of curcumin and its interaction with other drugs. Clinical studies have shown that curcumin is safe at the doses of 12 g/day but exhibits poor systemic bioavailability. The use of adjuvant like piperine, liposomal curcumin, curcumin nanoparticles and curcumin phospholipid complex has shown enhanced bioavailability and therapeutic potential. Further studies are warranted to prove the potential of curcumin against various ailments.
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Affiliation(s)
- Sita Sharan Patel
- Department of Pharmacy, Sagar Institute of Research and Technology, Bhopal, India
| | - Ashish Acharya
- Department of Pharmacy, Sagar Institute of Research and Technology, Bhopal, India
| | - R S Ray
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
| | - Ritesh Agrawal
- Department of Pharmacy, Sagar Institute of Research and Technology, Bhopal, India
| | - Ramsaneh Raghuwanshi
- Department of Pharmacy, Sagar Institute of Research and Technology, Bhopal, India
| | - Priyal Jain
- Department of Pharmacy, Sagar Institute of Research and Technology, Bhopal, India
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Boozari M, Butler AE, Sahebkar A. Impact of curcumin on toll-like receptors. J Cell Physiol 2019; 234:12471-12482. [PMID: 30623441 DOI: 10.1002/jcp.28103] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 12/02/2018] [Indexed: 12/25/2022]
Abstract
Toll-like receptors (TLRs) have a pivotal role in the activation of innate immune response and inflammation. TLRs can be divided into two subgroups including extracellular TLRs that recognize microbial membrane components (TLR1, 2, 4, 5, 6, and 10), and intracellular TLRs that recognize microbial nucleic acids (TLR3, 7, 8, and 9). Curcumin is a dietary polyphenol from Curcuma longa L. that is reputed to have diverse biological and pharmacological effects. Extensive research has defined the molecular mechanisms through which curcumin mediates its therapeutic effects. One newly defined and important target of curcumin is the TLR, where it exerts an inhibitory effect. In the current study, we focus upon the TLR antagonistic effect of curcumin and curcumin's therapeutic effect as mediated via TLR inhibition. The available evidence indicates that curcumin inhibits the extracellular TLR 2 and 4 and intracellular TLR9 and thereby exerts a therapeutic effect in diseases such as cancer, inflammation, infection, autoimmune, and ischemic disease. Curcumin effectively modulates the TLR response and thereby exerts its potent therapeutic effects.
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Affiliation(s)
- Motahare Boozari
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alexandra E Butler
- Diabetes Research Center, Qatar Biomedical Research Institute, Doha, Qatar
| | - Amirhossein Sahebkar
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Catanzaro M, Corsini E, Rosini M, Racchi M, Lanni C. Immunomodulators Inspired by Nature: A Review on Curcumin and Echinacea. Molecules 2018; 23:molecules23112778. [PMID: 30373170 PMCID: PMC6278270 DOI: 10.3390/molecules23112778] [Citation(s) in RCA: 117] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Revised: 10/22/2018] [Accepted: 10/24/2018] [Indexed: 02/06/2023] Open
Abstract
The immune system is an efficient integrated network of cellular elements and chemicals developed to preserve the integrity of the organism against external insults and its correct functioning and balance are essential to avoid the occurrence of a great variety of disorders. To date, evidence from literature highlights an increase in immunological diseases and a great attention has been focused on the development of molecules able to modulate the immune response. There is an enormous global demand for new effective therapies and researchers are investigating new fields. One promising strategy is the use of herbal medicines as integrative, complementary and preventive therapy. The active components in medical plants have always been an important source of clinical therapeutics and the study of their molecular pharmacology is an enormous challenge since they offer a great chemical diversity with often multi-pharmacological activity. In this review, we mainly analysed the immunomodulatory/antinflammatory activity of Echinacea spp. and Curcuma longa, focusing on some issues of the phytochemical research and on new possible strategies to obtain novel agents to supplement the present therapies.
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Affiliation(s)
- Michele Catanzaro
- Department of Drug Sciences-Pharmacology Section, University of Pavia, 27100 Pavia, Italy.
| | - Emanuela Corsini
- Department of Environmental Science and Policy, University of Milano, 20133 Milano, Italy.
| | - Michela Rosini
- Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy.
| | - Marco Racchi
- Department of Drug Sciences-Pharmacology Section, University of Pavia, 27100 Pavia, Italy.
| | - Cristina Lanni
- Department of Drug Sciences-Pharmacology Section, University of Pavia, 27100 Pavia, Italy.
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Downregulation of Interleukin- (IL-) 17 through Enhanced Indoleamine 2,3-Dioxygenase (IDO) Induction by Curcumin: A Potential Mechanism of Tolerance towards Helicobacter pylori. J Immunol Res 2018; 2018:3739593. [PMID: 30402507 PMCID: PMC6196794 DOI: 10.1155/2018/3739593] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 08/27/2018] [Indexed: 12/11/2022] Open
Abstract
The anti-inflammatory and antimicrobial properties of curcumin suggest its use as an anti-Helicobacter pylori (H. pylori) agent, but mechanisms underlying its helpful activity are still not clear. Indoleamine 2,3-dioxygenase (IDO) promotes the effector T cell apoptosis by catalyzing the rate-limiting first step in tryptophan catabolism, and its high expression in H. pylori-infected human gastric mucosa attenuates Th1 and Th17 immune response. The aim of this study was to investigate the role of curcumin in modulating the expression of IL-17 and IDO in H. pylori-infected human gastric mucosa. In an organ culture chamber, gastric biopsies from 35 patients were treated with and without 200 μM curcumin. In H. pylori-infected patients (n = 21), IL-17 was significantly lower, both in gastric biopsies (p = 0.0003) and culture supernatant (p = 0.0001) while IDO significantly increased (p < 0.00001) in curcumin-treated sample compared with untreated samples. In a subgroup of H. pylori-infected patients (n = 15), samples treated with curcumin in addition to IDO inhibitor 1-methyl-L-tryptophan (1-MT) showed a higher expression of IL-17 compared with untreated samples and curcumin-treated alone (p < 0.00001). Curcumin downregulates IL-17 production through the induction of IDO in H. pylori-infected human gastric mucosa, suggesting its role in dampening H. pylori-induced immune-mediated inflammatory changes.
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Santos AM, Lopes T, Oleastro M, Pereira T, Alves CC, Seixas E, Chaves P, Machado J, Guerreiro AS. Cyclooxygenase inhibition with curcumin in Helicobacter pylori infection. ACTA ACUST UNITED AC 2018. [DOI: 10.1186/s41110-018-0070-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Ma F, Liu F, Ding L, You M, Yue H, Zhou Y, Hou Y. Anti-inflammatory effects of curcumin are associated with down regulating microRNA-155 in LPS-treated macrophages and mice. PHARMACEUTICAL BIOLOGY 2017; 55:1263-1273. [PMID: 28264607 PMCID: PMC6130682 DOI: 10.1080/13880209.2017.1297838] [Citation(s) in RCA: 94] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
CONTEXT The natural polyphenolic compound curcumin has been proved to modulate innate immune responses and possess anti-inflammatory properties. Nevertheless, the mechanism remains poorly understood, particularly regarding curcumin-regulated miRNAs under inflammatory response. OBJECTIVE This study investigates the role of miRNA-155 in the effects of curcumin on inflammatory response in cell and a mouse model. MATERIALS AND METHODS The anti-inflammatory activity of curcumin (5, 10 and 15 μM, 2 h) in lipopolysaccharide (LPS, 200 ng/mL)-induced cells were measured by quantitative PCR. The animals were treated orally by 20 mg/kg curcumin for 3 days before an LPS intraperitoneal injection (10 mg/kg, 16 h). MicroRNA (miRNA) expression and the underlying molecular mechanisms were assessed using transfection technique and western blotting. RESULTS AND DISCUSSION Curcumin efficiently inhibited LPS-induced cytokines (TNF-α, IL-6) and microRNA-155 (miR-155) expression (p < 0.05) without affecting the normally growth of Raw264.7 and THP-1 cells (IC50 21.8 and 22.3 μM at 48 h, respectively). Moreover, the levels of cytokines were suppressed by curcumin in miR-155 mimics transfected cells (p < 0.05). A blockade of PI3K/AKT signalling pathways resulted in a decreased level of miR-155 (p < 0.05). Curcumin effectively protected mice from sepsis as evidenced by decreasing histological damage, reducing AST (352.0 vs 279.3 U/L), BUN (14.8 vs 10.8 mmol/L) levels and the proportion of macrophages in spleen (31.1% vs 13.5%). MicroRNA-155 level and cytokines were also reduced in curcumin-treated mice (p < 0.05). CONCLUSIONS Curcumin's ability to suppress LPS-induced inflammatory response may be due to the inhibition of miR-155.
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Affiliation(s)
- Feiya Ma
- The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, PR China
| | - Fei Liu
- The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, PR China
| | - Liang Ding
- The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, PR China
| | - Ming You
- The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, PR China
| | - Huimin Yue
- The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, PR China
| | - Yujie Zhou
- The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, PR China
- Yujie ZhouThe Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing210008, China
| | - Yayi Hou
- The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, PR China
- Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, PR China
- CONTACT Yayi HouMedical School, Nanjing University, Nanjing210093, China
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Zarei M, Mosayebi G, Khansarinejad B, Abtahi H. Antigenic and immunogenic evaluation of Helicobacter pylori FlaA epitopes. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2017; 20:920-926. [PMID: 29085584 PMCID: PMC5651478 DOI: 10.22038/ijbms.2017.9115] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Objective(s): Helicobacter pylori are among most common human pathogens affecting at least half of the world’s population. Mobility is one of the important primary factors in bacterial colonization and invasion. The purpose of this research is cloning, expression, and purification of FlaA protein specific epitopes in order to evaluate their antigenicity and immunogenicity. Materials and Methods: The antigenic region of the flaA gene was bioinformatically predicted using Epitope mapping software’s and the predicted epitopes were expressed in a prokaryotic expression vector. The antigen was injected into the animal model (mice BALB/c) and some indicators including IgG1, IgG2a, IgA, IFN-γ, and IL 5 were measured. Results: The immunogenicity studies in animal models by measuring serum antibodies (IgG1, IgG2a, and IgA) and cytokines (IFN-γ and IL5) revealed that the rFlaA induces a proper immune response in animal models. Conclusion: The recombinant FlaA protein is antigenic and immunogenic. Therefore, it might be used in order to design of specific diagnostic kits and recombinant vaccines against H. pylori.
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Affiliation(s)
- Mansoor Zarei
- Department of Medical Biotechnology, School of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Ghasem Mosayebi
- Department of Microbiology and Immunology, School of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Behzad Khansarinejad
- Department of Microbiology and Immunology, School of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Hamid Abtahi
- Molecular and Medicine Research Center, Department of Microbiology and Immunology, School of Medicine, Arak University of Medical Sciences, Arak, Iran
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Effect of Curcumin on the Diversity of Gut Microbiota in Ovariectomized Rats. Nutrients 2017; 9:nu9101146. [PMID: 29048369 PMCID: PMC5691762 DOI: 10.3390/nu9101146] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Revised: 10/15/2017] [Accepted: 10/17/2017] [Indexed: 02/06/2023] Open
Abstract
Curcumin has been proven to have a weight-loss effect in a menopausal rat model induced by ovariectomy. However, the effects of curcumin on gut microfloral communities of ovariectomized (OVX) rats remains unclear. Here, we used high-throughput 16S rDNA sequencing to explore the effects of curcumin on microbial diversity in the gut of OVX rats. Female Wistar rats were subjected to either ovariectomy or a sham operation (SHAM group). The OVX rats were treated with vehicle (OVX group) or curcumin (CUR group) by oral gavage. After 12-week treatments, the weights of the bodies and uteri of rats were recorded, the levels of estradiol in the serum were assayed by electrochemiluminescence immunoassay (ECLIA). Then, the fragments encompassing V3–V4 16S rDNA hypervariable regions were PCR amplified from fecal samples, and the PCR products of V3–V4 were sequenced on an Illumina MiSeq for characterization of the gut microbiota. Our results showed that, compared to rats in the SHAM group, rats in the OVX group had more weight gain and lower levels of estradiol in the serum, and curcumin could cause significant weight loss in OVX rats but did not increase the levels of estradiol. Sequencing results revealed the presence of 1120, 1114, and 1119 operational taxonomic units (OTUs) found in the SHAM, OVX, and CUR groups, respectively. The percentage of shared OTUs was 86.1603%. Gut microbiota of rats from the SHAM or CUR group had higher levels of biodiversity and unevenness estimations than those from the OVX group. At the phyla level, compared to rats in SHAM group, rats in the OVX group had a higher ratio of phyla Firmicutes and Bacteroidetes in the gut; at the genus level, four differential gut microbiota (Incertae_Sedis, Anaerovorax, Anaerotruncus, and Helicobacter) between SHAM and OVX groups were found, whereas seven differential gut microbiota (Serratia, Anaerotruncus, Shewanella, Pseudomonas, Papillibacter, Exiguobacterium, and Helicobacter) between OVX and CUR groups were found. In conclusion, estrogen deficiency induced by ovariectomy caused changes in the distribution and structure of intestinal microflora in rats, and curcumin could partially reverse changes in the diversity of gut microbiota.
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JUDAKI A, RAHMANI A, FEIZI J, ASADOLLAHI K, HAFEZI AHMADI MR. CURCUMIN IN COMBINATION WITH TRIPLE THERAPY REGIMES AMELIORATES OXIDATIVE STRESS AND HISTOPATHOLOGIC CHANGES IN CHRONIC GASTRITIS-ASSOCIATED HELICOBACTER PYLORI INFECTION. ARQUIVOS DE GASTROENTEROLOGIA 2017; 54:177-182. [DOI: 10.1590/s0004-2803.201700000-18] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Accepted: 02/15/2017] [Indexed: 02/08/2023]
Abstract
ABSTRACT BACKGROUND Helicobacter pylori (H. pylori) gastric infection is a main cause of inflammatory changes and gastric cancers. OBJECTIVE The aim of this study was finding the effects of curcumin on oxidative stress and histological changes in chronic gastritis associated with H. pylori. METHODS In a randomized clinical trial, patients were divided into two groups: a standard triple therapy group and triple therapy with curcumin group. Endoscopic and histological examinations were measured for all patients before and after 8 weeks. RESULTS Triple therapy with curcumin treatment group significantly decreased malondialdehyde markers, glutathione peroxides and increased total antioxidant capacity of the gastric mucosa at the end of study compared to baseline and triple regimen groups. In addition, the oxidative damage to DNA was significantly decreased in triple therapy with curcumin group at the end of study compared to baseline and compared to triple therapy (P<0.05 for both). Triple therapy group in combination with Curcumin significantly decreased all active, chronic and endoscopic inflammation scores of patients compared to the baseline and triple therapy group (P<0.05 for both). The eradication rate by triple therapy + curcumin was significantly increased compared to triple therapy alone (P<0.05). CONCLUSION Curcumin can be a useful supplement to improve chronic inflammation and prevention of carcinogenic changes in patients with chronic gastritis associated by H. pylori.
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Erratum to effects of curcumin on Helicobacter pylori infection. ANNALS OF TRANSLATIONAL MEDICINE 2017; 5:153. [PMID: 28462233 PMCID: PMC5395484 DOI: 10.21037/atm.2017.03.13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2024]
Abstract
[This corrects the article DOI: 10.21037/atm.2016.12.52.].
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McClure R, Ong H, Janve V, Barton S, Zhu M, Li B, Dawes M, Jerome WG, Anderson A, Massion P, Gore JC, Pham W. Aerosol Delivery of Curcumin Reduced Amyloid-β Deposition and Improved Cognitive Performance in a Transgenic Model of Alzheimer's Disease. J Alzheimers Dis 2017; 55:797-811. [PMID: 27802223 PMCID: PMC5848215 DOI: 10.3233/jad-160289] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
We report a novel approach for the delivery of curcumin to the brain via inhalation of the aerosol for the potential treatment of Alzheimer's disease. The percentage of plaque fraction in the subiculum and hippocampus reduced significantly when young 5XFAD mice were treated with inhalable curcumin over an extended period of time compared to age-matched nontreated counterparts. Further, treated animals demonstrated remarkably improved overall cognitive function, no registered systemic or pulmonary toxicity associated with inhalable curcumin observed during the course of this work.
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Affiliation(s)
- Richard McClure
- Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA
- Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA
- Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA
| | - Henry Ong
- Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA
- Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA
| | - Vaibhab Janve
- Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA
- Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA
| | - Shawn Barton
- Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA
- Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA
| | - Meiying Zhu
- Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA
- Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA
| | - Bo Li
- Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA
- Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA
| | - Mary Dawes
- Vanderbilt Cell Imaging Core Laboratory, Nashville, TN, USA
| | - W. Gray Jerome
- Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA
| | - Adam Anderson
- Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA
- Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA
- Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA
| | - Pierre Massion
- Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA
| | - John C. Gore
- Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA
- Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA
- Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA
- Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA
| | - Wellington Pham
- Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA
- Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA
- Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA
- Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA
- Vanderbilt Institute of Chemical Biology, Nashville, TN, USA
- Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA
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Vetvicka V, Vetvickova J, Fernandez-Botran R. Effects of curcumin on Helicobacter pylori infection. ANNALS OF TRANSLATIONAL MEDICINE 2016; 4:479. [PMID: 28149841 PMCID: PMC5233496 DOI: 10.21037/atm.2016.12.52] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Accepted: 11/28/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND Curcumin is a well-established natural molecule with significant biological and pharmaceutical effects. Its effects on Helicobacter pylori (H. pylori) infection have been repeatedly confirmed both in animal and human models. This study directly compared five different samples to evaluate if the effects are general or if they differ among samples. METHODS Using a mouse model, we studied the effects of curcumin on lipid peroxide (LPO) level, myeloperoxidase (MPO) and urease activity, number of colonized bacteria, levels of anti-H. pylori antibodies, biofilm formation, IFN-γ, IL-4, gastrin and somatostatin levels in serum, and minimum inhibitory concentration. In addition, we evaluated the effects on biofilm production and antibacterial antibody response. RESULTS In all tests, one sample (Sabinsa) was consistently the most active. CONCLUSIONS All curcumin samples showed some anti-H. pylori effects, but only some of the tested samples had significant activity.
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Affiliation(s)
- Vaclav Vetvicka
- Department of Pathology, University of Louisville, Louisville, KY, USA
| | - Jana Vetvickova
- Department of Pathology, University of Louisville, Louisville, KY, USA
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Curcumin Shows Antiviral Properties against Norovirus. Molecules 2016; 21:molecules21101401. [PMID: 27775614 PMCID: PMC6274093 DOI: 10.3390/molecules21101401] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Revised: 10/07/2016] [Accepted: 10/15/2016] [Indexed: 11/17/2022] Open
Abstract
Phytochemicals provide environmentally friendly and relatively inexpensive natural products, which could potentially benefit public health by controlling human norovirus (HuNoV) infection. In this study, 18 different phytochemicals were evaluated for antiviral effects against norovirus using murine norovirus (MNV) as a model for norovirus biology. Among these phytochemicals, curcumin (CCM) was the most potent anti-noroviral phytochemical, followed by resveratrol (RVT). In a cell culture infection model, exposure to CCM or RVT for 3 days reduced infectivity of norovirus by 91% and 80%, respectively. To confirm the antiviral capability of CCM, we further evaluated its antiviral efficacy at various doses (0.25, 0.5, 0.75, 1, and 2 mg/mL) and durations (short-term: 10, 30, 60, and 120 min; long-term: 1, 3, 7, and 14 days). The anti-noroviral effect of CCM was verified to occur in a dose-dependent manner. Additionally, we evaluated the inhibitory effect of each phytochemical on the replication of HuNoV using a HuNoV replicon-bearing cell line (HG23). Neither CCM nor RVT had a strong inhibitory effect on HuNoV replication, which suggests that their antiviral mechanism may involve viral entry or other life cycle stages rather than the replication of viral RNA. Our results demonstrated that CCM may be a promising candidate for development as an anti-noroviral agent to prevent outbreaks of foodborne illness.
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Rana S, Kumar S, Rathore N, Padwad Y, Bhushana S. Nutrigenomics and its Impact on Life Style Associated Metabolic Diseases. Curr Genomics 2016; 17:261-78. [PMID: 27252592 PMCID: PMC4869012 DOI: 10.2174/1389202917666160202220422] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 06/18/2015] [Accepted: 06/22/2015] [Indexed: 02/07/2023] Open
Abstract
Post-human genome revelation observes the emergence of 'Nutigenomics' as one of the exciting scientific advancement influencing mankind around the world. Food or more precisely 'nutrition' has the major impact in defining the cause-response interaction between nutrient (diet) and human health. In addition to substantial understanding of nutrition-human-health interaction, bases of 'nutrigenomic' development foster on advent in transcriptomics, genomics, proteomics and metabolomics as well as insight into food as health supplement. Interaction of selected nutrient with associated genes in specific organ or tissue necessary to comprehend that how individual's genetic makeup (DNA transcribed into mRNA and then to proteins) respond to particular nutrient. It provided new opportunities to incorporate natural bioactive compounds into food for specific group of people with similar genotype. As inception of diabetes associated with change in gene expression of, not limited to, protein kinase B, insulin receptor, duodenal homeobox and glucokinase, thus, targeting such proteins by modifying or improving the nutritional availability or uptake may help to devise novel food, supplements, or nutraceuticals. In this article, various aspects of R&D in nutrigenomics are reviewed to ascertain its impact on human health, especially with life-style associated diseases.
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Affiliation(s)
- Shalika Rana
- Department of Biotechnology, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176 061 (HP), India
- Academy of Scientific and Innovative Research, CSIR-Institute of Himalayan Bioresource Technology,
Palampur176 061 (HP), India
| | - Shiv Kumar
- Pharmacology and Toxicology Lab, Department of Food Nutraceuticals and Quality
Control, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176 061 (HP), India
- Academy of Scientific and Innovative Research, CSIR-Institute of Himalayan Bioresource Technology,
Palampur176 061 (HP), India
| | - Nikita Rathore
- Department of Biotechnology, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176 061 (HP), India
| | - Yogendra Padwad
- Pharmacology and Toxicology Lab, Department of Food Nutraceuticals and Quality
Control, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176 061 (HP), India
- Academy of Scientific and Innovative Research, CSIR-Institute of Himalayan Bioresource Technology,
Palampur176 061 (HP), India
| | - Shashi Bhushana
- Department of Biotechnology, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176 061 (HP), India
- Academy of Scientific and Innovative Research, CSIR-Institute of Himalayan Bioresource Technology,
Palampur176 061 (HP), India
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Shmuely H, Domniz N, Yahav J. Non-pharmacological treatment of Helicobacter pylori. World J Gastrointest Pharmacol Ther 2016; 7:171-178. [PMID: 27158532 PMCID: PMC4848239 DOI: 10.4292/wjgpt.v7.i2.171] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 10/12/2015] [Accepted: 02/16/2016] [Indexed: 02/06/2023] Open
Abstract
Many food and plant extracts have shown in vitro anti-Helicobacter pylori (H. pylori) activity, but are less effective in vivo. The anti-H. pylori effects of these extracts are mainly permeabilitization of the membrane, anti-adhesion, inhibition of bacterial enzymes and bacterial grown. We, herein, review treatment effects of cranberry, garlic, curcumin, ginger and pistacia gum against H. pylori in both in vitro, animal studies and in vivo studies.
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Sarkar A, De R, Mukhopadhyay AK. Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases. World J Gastroenterol 2016; 22:2736-2748. [PMID: 26973412 PMCID: PMC4777996 DOI: 10.3748/wjg.v22.i9.2736] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 01/01/2016] [Accepted: 01/18/2016] [Indexed: 02/06/2023] Open
Abstract
Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, anti-oxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori (H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake.
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Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Ramirez-Tortosa M. Curcumin and Health. Molecules 2016; 21:264. [PMID: 26927041 PMCID: PMC6273481 DOI: 10.3390/molecules21030264] [Citation(s) in RCA: 352] [Impact Index Per Article: 39.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Revised: 02/08/2016] [Accepted: 02/22/2016] [Indexed: 12/14/2022] Open
Abstract
Nowadays, there are some molecules that have shown over the years a high capacity to act against relevant pathologies such as cardiovascular disease, neurodegenerative disorders or cancer. This article provides a brief review about the origin, bioavailability and new research on curcumin and synthetized derivatives. It examines the beneficial effects on health, delving into aspects such as cancer, cardiovascular effects, metabolic syndrome, antioxidant capacity, anti-inflammatory properties, and neurological, liver and respiratory disorders. Thanks to all these activities, curcumin is positioned as an interesting nutraceutical. This is the reason why it has been subjected to several modifications in its structure and administration form that have permitted an increase in bioavailability and effectiveness against different diseases, decreasing the mortality and morbidity associated to these pathologies.
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Affiliation(s)
- Mario Pulido-Moran
- Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Campus Universitario de Cartuja, Universidad de Granada, 18071 Granada, Spain.
- Instituto de Nutrición y Tecnología de los Alimentos José Mataix Verdú, Centro de Investigaciones Biomédicas, Avenida del Conocimiento s/n, Campus Tecnológico y Ciencias de la Salud, Universidad de Granada, Armilla (Granada) 18016, Spain.
| | - Jorge Moreno-Fernandez
- Instituto de Nutrición y Tecnología de los Alimentos José Mataix Verdú, Centro de Investigaciones Biomédicas, Avenida del Conocimiento s/n, Campus Tecnológico y Ciencias de la Salud, Universidad de Granada, Armilla (Granada) 18016, Spain.
- Departamento de Fisiología, Facultad de Farmacia, Campus Universitario de Cartuja, Universidad de Granada, 18071 Granada, Spain.
| | | | - Mcarmen Ramirez-Tortosa
- Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Campus Universitario de Cartuja, Universidad de Granada, 18071 Granada, Spain.
- Instituto de Nutrición y Tecnología de los Alimentos José Mataix Verdú, Centro de Investigaciones Biomédicas, Avenida del Conocimiento s/n, Campus Tecnológico y Ciencias de la Salud, Universidad de Granada, Armilla (Granada) 18016, Spain.
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The Protective Effects of 18β-Glycyrrhetinic Acid on Helicobacter pylori-Infected Gastric Mucosa in Mongolian Gerbils. BIOMED RESEARCH INTERNATIONAL 2016; 2016:4943793. [PMID: 27006947 PMCID: PMC4783533 DOI: 10.1155/2016/4943793] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Revised: 01/14/2016] [Accepted: 01/21/2016] [Indexed: 12/13/2022]
Abstract
18β-Glycyrrhetinic acid (GRA), a major component of Glycyrrhiza glabra, is widely used therapeutically in clinic. In this study, the effect of GRA on Helicobacter pylori- (H. pylori-) infected gastritis was investigated in Mongolian gerbils in vivo. The gerbils were randomly divided into groups: uninfected; H. pylori-infected; H. pylori + antibiotics (clarithromycin, amoxicillin, and esomeprazole); and H. pylori + GRA. The gastric intraluminal pH value, histopathological changes, and the expression levels of inflammation-related cytokines (IL-1β, TNF-α, COX-2, and iNOS) were investigated. The results showed that, in the H. pylori + GRA group, the intraluminal gastric pH value was lower (2.14 ± 0.08 versus 3.17 ± 0.23, P < 0.05), erosion and hyperplasia were alleviated, the infiltration of neutrophils and mononuclear cells was attenuated (P < 0.05), and the expression levels of TNF-α, IL-1β, COX-2, and iNOS were decreased (P < 0.05) compared with the H. pylori-infected group. There was no significant difference in results between the H. pylori + GRA group and the H. pylori + antibiotics group. This study indicated that GRA significantly attenuated H. pylori-infected gastritis in gerbils and has the potential to be developed as a new therapeutic drug.
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Fattori V, Amaral FA, Verri WA. Neutrophils and arthritis: Role in disease and pharmacological perspectives. Pharmacol Res 2016; 112:84-98. [PMID: 26826283 DOI: 10.1016/j.phrs.2016.01.027] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2015] [Revised: 01/20/2016] [Accepted: 01/21/2016] [Indexed: 12/25/2022]
Abstract
The inflammatory response in the joint can induce an intense accumulation of leukocytes in the tissue that frequently results in severe local damage and loss of function. Neutrophils are essential cells to combat many pathogens, but their arsenal can contribute or aggravate articular inflammation. Here we summarized some aspects of neutrophil biology, their role in inflammation and indicated how the modulation of neutrophil functions could be useful for the treatment of different forms of arthritis.
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Affiliation(s)
- Victor Fattori
- Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil
| | - Flavio A Amaral
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Laboratório de Imunofarmacologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
| | - Waldiceu A Verri
- Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
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Structural Interactions of Curcumin Biotransformed Molecules with the N-Terminal Residues of Cytotoxic-Associated Gene A Protein Provide Insights into Suppression of Oncogenic Activities. Interdiscip Sci 2016; 9:116-129. [PMID: 26798036 DOI: 10.1007/s12539-016-0142-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Revised: 12/21/2015] [Accepted: 01/04/2016] [Indexed: 01/01/2023]
Abstract
Curcumin as a natural product has drawn considerable attention in recent years for its multiple pharmacological activities against various diseases, but more studies are required to understand the curcumin pharmacological action considering its low bioavailability. Though numerous reasons contribute to the low bioavailability of curcumin, one of the important reasons is associated with biotransformation of curcumin through either conjugation or reduction depending on curcumin administration route. The orally administered curcumin (CUR) is metabolised into curcumin glucuronidase (CUR-GLR) and curcumin sulphate by conjugation, whereas dihydroxycurcumin, tetrahydrocurcumin, and hexahydrocurcumin (HHC) are formed by reduction after intraperitoneal administration of curcumin. The main aim of the current study was to investigate the pharmacological properties of curcumin and its biotransformed molecules and its inhibitory potential against CagA (cytotoxic-associated gene A) oncoprotein of Helicobacter pylori. All lead molecules followed the Lipinski's five rules for biological activities, except CUR-GLR, whereas druglikeness scores were obtained for all molecules. Subsequently, molecular docking was employed to analyse the binding affinity of molecules with CagA. The docking studies revealed that CUR-GLR has highest binding affinity with CagA, whereas less interactive affinity was observed in HHC. From the virtual screening and docking studies, the current study suggests that the biotransformation of curcumin through conjugation has more potential for inhibition of oncogenic activities of CagA+ H. pylori than reduction.
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Kim A, Lim JW, Kim H, Kim H. Supplementation with Angelica keiskei inhibits expression of inflammatory mediators in the gastric mucosa of Helicobacter pylori-infected mice. Nutr Res 2016; 36:488-97. [PMID: 27101766 DOI: 10.1016/j.nutres.2015.12.017] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2015] [Revised: 12/31/2015] [Accepted: 12/31/2015] [Indexed: 12/23/2022]
Abstract
Oxidative stress is involved in the pathogenesis of Helicobacter pylori-associated gastric ulceration and carcinogenesis. The oxidant-sensitive transcription factor, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), regulates expression of inflammatory mediators such as interferon γ (IFN-γ), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). These inflammatory mediators increased in gastric mucosal tissues from patients infected with H pylori. Angelica keiskei (AK), a green leafy vegetable, is rich in carotenoids and flavonoids and shows antioxidant and anti-inflammatory activities. Therefore, we hypothesized that AK may protect the gastric mucosa of H pylori-infected mice against inflammation. We determined lipid peroxide abundance, myeloperoxidase activity, expression levels of inflammatory mediators (IFN-γ, COX-2, and iNOS), NF-κB-DNA binding activity, and histologic changes in gastric mucosal tissues. The antioxidant N-acetylcysteine served as the positive control treatment. Supplementation with AK suppressed increases in lipid peroxide abundance, myeloperoxidase activity, induction of inflammatory mediators (IFN-γ, COX-2, and iNOS), activation of NF-κB, and degradation of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor α in gastric mucosal tissue from H pylori-infected mice. Inhibition of H pylori-induced alterations by AK was similar to that by N-acetylcysteine. Taken together, these results suggest that supplementation with AK may prevent H pylori-induced gastric inflammation by inhibiting NF-κB-mediated induction of inflammatory mediators in the gastric mucosa of patients infected with H pylori.
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Affiliation(s)
- Aryoung Kim
- Department of Food and Nutrition, Brian Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Republic of Korea
| | - Joo Weon Lim
- Department of Food and Nutrition, Brian Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Republic of Korea
| | - Hoguen Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Hyeyoung Kim
- Department of Food and Nutrition, Brian Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Republic of Korea.
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Srivastava AK, Kumar V, Roy BK. Insights from the molecular docking of curcumin to the virulent factors of Helicobacter pylori. Bioinformation 2015; 11:447-53. [PMID: 26664028 PMCID: PMC4658642 DOI: 10.6026/97320630011447] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Accepted: 10/01/2015] [Indexed: 12/11/2022] Open
Abstract
The domains of virulent (Ureα/β, VacA-p55, and CagA) factors of Helicobacter pylori play a pivotal role in developmental processes of numerous diseases including gastric cancer. The pharmacological role of curcumin indicates that it could regulate the signaling of virulent factors by interacting with active domains. However, the controlling mechanism of the curcumin interactions and the binding diversity on structural basis of virulent (Ureα/β, VacA-p55, and CagA) factors are unknown. Curcumin as therapeutic agent was filtered by using Lipinski rule׳s five and the druglikeness property for assessment of pharmacological properties. Here outcome of molecular docking presented the 3-D structure of curcumin complex, that interacted with especially conserved residues of target domains. The structure revealed that the curcumin complexation with domains of these proteins provided structural insight into the diverse nature of proteins (Ureα/β, VacA-p55, and CagA) recognition. In silico study elucidated that the broad specificity of curcumin was achieved by multiple binding mode mechanisms such as distinct hydrogen and hydrophobic interactions with involvement of binding energy. The higher score of curcumin in complexation with both subunits Ureα/β showed the stable binding, and less stability with VacA-p55 complexation with lower score. Curcumin exhibited good interaction with these targeted virulent factors, although extensive interactions of curcumin with Ureα/β subunits could have an important implication to prevent survival and colonisation of H. pylori in stomach.
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Affiliation(s)
| | - Vikas Kumar
- Department of Botany, Banaras Hindu University, Varanasi, 221005, India
| | - Bijoy Krishna Roy
- Department of Botany, Banaras Hindu University, Varanasi, 221005, India
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Padmanaban G, Rangarajan PN. Curcumin as an Adjunct Drug for Infectious Diseases. Trends Pharmacol Sci 2015; 37:1-3. [PMID: 26521094 DOI: 10.1016/j.tips.2015.09.007] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Accepted: 09/23/2015] [Indexed: 10/22/2022]
Abstract
Curcumin, by virtue of its ability to function as an immunomodulator, has the potential to serve as an adjunct drug to treat infectious diseases and provide long-term protection. The current need is to establish clinical trials with curcumin as an adjunct drug against specific infectious diseases.
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Affiliation(s)
| | - Pundi N Rangarajan
- Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India
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Yazbek PB, Trindade AB, Chin CM, Dos Santos JL. Challenges to the Treatment and New Perspectives for the Eradication of Helicobacter pylori. Dig Dis Sci 2015; 60:2901-12. [PMID: 25999247 DOI: 10.1007/s10620-015-3712-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Accepted: 05/07/2015] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori (H. pylori) is one of the leading causes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric adenocarcinoma. The current treatment of H. pylori infection with antibiotics and proton pump inhibitors has several limitations, including poor adherence and intrinsic patient-related factors, drug resistance, and the absence of adequate treatments. This review summarizes the current therapeutic approaches to eradicating H. pylori, the difficulties associated with its treatment, and several new perspectives aimed at improving existing treatment strategies.
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Affiliation(s)
- Priscila Baptistella Yazbek
- School of Pharmaceutical Science, Drugs and Medicines Department, State University of São Paulo "Júlio de Mesquita Filho", Rodovia Araraquara Jaú Km, 01 s/n, Araraquara, SP, 14801-902, Brazil
| | - Ariane Biolcati Trindade
- School of Pharmaceutical Science, Drugs and Medicines Department, State University of São Paulo "Júlio de Mesquita Filho", Rodovia Araraquara Jaú Km, 01 s/n, Araraquara, SP, 14801-902, Brazil
| | - Chung Man Chin
- School of Pharmaceutical Science, Drugs and Medicines Department, State University of São Paulo "Júlio de Mesquita Filho", Rodovia Araraquara Jaú Km, 01 s/n, Araraquara, SP, 14801-902, Brazil
| | - Jean Leandro Dos Santos
- School of Pharmaceutical Science, Drugs and Medicines Department, State University of São Paulo "Júlio de Mesquita Filho", Rodovia Araraquara Jaú Km, 01 s/n, Araraquara, SP, 14801-902, Brazil.
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Srivastava AK, Tewari M, Shukla HS, Roy BK. In Silico Profiling of the Potentiality of Curcumin and Conventional Drugs for CagA Oncoprotein Inactivation. Arch Pharm (Weinheim) 2015; 348:548-555. [PMID: 25996140 DOI: 10.1002/ardp.201400438] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Revised: 04/16/2015] [Accepted: 04/17/2015] [Indexed: 01/04/2025]
Abstract
The oncoprotein cytotoxic associated gene A (CagA) of Helicobacter pylori plays a pivotal role in the development of gastric cancer, so it has been an important target for anti-H. pylori drugs. Conventional drugs are currently being implemented against H. pylori. The inhibitory role of plant metabolites like curcumin against H. pylori is still a major scientific challenge. Curcumin may represent a novel promising drug against H. pylori infection without producing side effects. In the present study, a comparative analysis between curcumin and conventional drugs (clarithromycin, amoxicillin, pantoprazole, and metronidazole) was carried out using databases to investigate the potential of curcumin against H. pylori targeting the CagA oncoprotein. Curcumin was filtered using Lipinski's rule of five and the druglikeness property for evaluation of pharmacological properties. Subsequently, molecular docking was employed to determine the binding affinities of curcumin and conventional drugs to the CagA oncoprotein. According to the results obtained from FireDock, the binding energy of curcumin was higher than those of amoxicillin, pantoprazole, and metronidazole, except for clarithromycin, which had the highest binding energy. Accordingly, curcumin may become a promising lead compound against CagA+ H. pylori infection.
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Affiliation(s)
| | - Mallika Tewari
- Department of Surgical Oncology, Banaras Hindu University, Varanasi, India
| | - Hari S Shukla
- Department of Surgical Oncology, Banaras Hindu University, Varanasi, India
| | - Bijoy K Roy
- Department of Botany, Banaras Hindu University, Varanasi, India
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