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Sun W, Zhang C, Xu J, Zhao M, Li P. Natural small-molecule compounds targeting Helicobacter pylori virulence factors: A promising strategy for overcoming antibiotic resistance. Biochem Biophys Res Commun 2025; 768:151877. [PMID: 40334425 DOI: 10.1016/j.bbrc.2025.151877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 04/15/2025] [Accepted: 04/22/2025] [Indexed: 05/09/2025]
Abstract
Helicobacter pylori (H. pylori) infection is an important causal factor of gastritis, peptic ulcer, and gastric cancer. High infection rates and the increasing challenge of antibiotic resistance worldwide have prompted an urgent need to develop novel therapeutic options and antimicrobial agents. This review focuses on the potential of natural small-molecule compounds as novel anti-H. pylori agents-a promising approach that mitigates the risk of resistance development and maintains the microbiome's ecological balance. We detail how H. pylori virulence factors, including urease, CagA, VacA, and biofilm, contribute to pathogenicity and underline the reassuring fact that naturally derived compounds sourced from plants and microorganisms have shown remarkable efficacy in inhibiting these virulence factors. Some compounds also exhibit synergistic effects with conventional antibiotics, potentially overcoming challenges associated with resistant strains. Furthermore, we discuss recent advancements in identifying novel drug targets within the H. pylori virulence spectrum, offering insights into future directions for research and development in H. pylori therapy.
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Affiliation(s)
- Wenjing Sun
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China; State Key Laboratory of Digestive Health, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing, 100050, China
| | - Congen Zhang
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, 100050 Beijing, China
| | - Junxuan Xu
- State Key Laboratory of Digestive Health, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing, 100050, China.
| | - Mengran Zhao
- State Key Laboratory of Digestive Health, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing, 100050, China.
| | - Peng Li
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China; State Key Laboratory of Digestive Health, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing, 100050, China.
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Jaiswal N, Kandpal M, Jha HC, Kumar A. Collective in-silico and in-vitro evaluation indicate natural phenolics as a potential therapeutic candidate targeting antimicrobial-resistant genes of Helicobacter pylori. Int J Biol Macromol 2025; 307:142197. [PMID: 40107545 DOI: 10.1016/j.ijbiomac.2025.142197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 02/28/2025] [Accepted: 03/15/2025] [Indexed: 03/22/2025]
Abstract
Antibiotic-resistant Helicobacter pylori is a major cause of severe gastric conditions such as ulcers and gastric cancer, with limited treatment options due to the rise of multidrug-resistant strains. This study aims to identify novel drug targets within antimicrobial resistance (AMR) genes and evaluate potential therapeutic candidates using computational and experimental approaches. AMR genes in H. pylori were identified using RAST and their essentiality, metabolic pathways, and druggability. Localization, protein family, and functional annotations were performed using QuickGO and Pfam, while Cytoscape was used for protein interaction analysis and identification of hub proteins. Ddl was selected as the target protein for further study among the AMR genes. Using the PASS tool, two phenolic compounds were identified as potential inhibitors of Ddl, and their interaction potency was confirmed through molecular docking studies. In-vitro experiments demonstrated that α-mangostin significantly attenuated H. pylori-mediated inflammatory responses in the gastric environment. Notably, α-mangostin induced the mitochondrial-mediated intrinsic apoptotic pathway in gastric epithelial cells, offering new insights into its therapeutic potential. This study identified Ddl as a promising drug target among AMR genes in H. pylori and highlighted phenolic compounds, particularly α-mangostin, as potential inhibitors. These findings contribute to the development of novel anti-H. pylori therapies address the growing challenge of antibiotic resistance and pave the way for future research into effective treatments for H. pylori infections.
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Affiliation(s)
- Neha Jaiswal
- Department of Biotechnology, National Institute of Technology, Raipur 492010, Chhattisgarh, India
| | - Meenakshi Kandpal
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore 453552, Madhya Pradesh, India
| | - Hem Chandra Jha
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore 453552, Madhya Pradesh, India.
| | - Awanish Kumar
- Department of Biotechnology, National Institute of Technology, Raipur 492010, Chhattisgarh, India.
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Asadi GS, Abdizadeh R, Abdizadeh T. Investigation of a set of flavonoid compounds as Helicobacter pylori urease inhibitors: insights from in silico studies. J Biomol Struct Dyn 2025; 43:2366-2388. [PMID: 38153379 DOI: 10.1080/07391102.2023.2295973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Accepted: 08/26/2023] [Indexed: 12/29/2023]
Abstract
Helicobacter pylori (H. pylori) is a spiral, microaerophilic gram-negative bacterium, which is associated with the destruction of the lining of the stomach, leads to chronic inflammation of the stomach, which can cause stomach and duodenal ulcers. The problems caused by the treatment with antibiotics have caused researchers to use new approaches to treat infections caused by H. pylori, among them specific treatments with flavonoids. Urease enzyme, as one of the most important pathogenic and antigenic factors of this bacterium, is a suitable target for this purpose. In this study, the inhibitory effect of flavonoid compounds compared to acetohydroxamic acid on H. pylori urease enzyme was evaluated using molecular modeling methods. First, the interaction of flavonoids with urease enzyme compared with acetohydroxamic acid was investigated by molecular docking method to produce efficient docking poses. Then the physicochemical properties and toxicity of the best flavonoid compounds were analyzed using the swissadme server. Also, molecular dynamics calculations were performed to precisely understand the interactions between ligands and protein. The results of this study show that all the investigated flavonoid compounds are capable of inhibiting H. pylori urease. Among these compounds, six compounds chrysin, galangin, kaempferol, luteolin, morin and quercetin showed a greater tendency to bind to urease, compared to the acetohydroxamic acid inhibitor. These compounds are desirable in terms of physicochemical properties. This study also revealed that the flavonoids with their hydroxyl groups (-OH) play an important role during bond formation with amino acids Ala278, Ala169, His314, Asp362 and Asn168. Therefore, flavonoid compounds, due to their suitable location in the active site of the urease, create a more effective inhibition than the chemical drug acetohydroxamic acid and can be suitable candidates for the treatment of Helicobacter pylori under in vitro and in vivo investigations.
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Affiliation(s)
- Golnoush Sadat Asadi
- Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran
- Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Rahman Abdizadeh
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Tooba Abdizadeh
- Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
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Lu Q, Wang J, Tang Y, Li W, Li C. Phytochemical analysis of dried ginger extract and its inhibitory effect and mechanism on Helicobacter pylori and associated ureases. Food Funct 2025; 16:1100-1115. [PMID: 39831446 DOI: 10.1039/d4fo04991h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2025]
Abstract
Helicobacter pylori (H. pylori), one of the most common infectious pathogens in the world, can cause gastritis, digestive ulcers, and even gastric cancer. H. pylori urease (HPU) is a distinctive virulence factor of H. pylori that allows it to be distinguished from other pathogens. Dried ginger is a famous edible and medicinal herb that is commonly used to prevent and treat gastrointestinal tract-related diseases. In this study, phytochemical analysis of the aqueous extract of dried ginger (DGE) and the inhibition of DGE on H. pylori was investigated. Subsequently, we evaluated the inhibitory activity of DGE against enzymes including HPU and jack bean urease (JBU) and determined its potential mechanism of action. UPLC-ESI-MS/MS analysis indicated that a total of 63 compounds including seven glycosides, nine terpenoids, two esters, seven phenols, eight lignans, five phenylpropanoids, and four phenolic acids were identified in DGE. DGE was observed to inhibit the growth of four H. pylori strains (ATCC 43504, NCTC 26695, SS1, and ICDC 111001) with minimum inhibitory concentration (MIC) values spanning the range of 0.05 to 1.50 mg mL-1. Moreover, DGE has higher enzyme inhibitory activity on HPU (IC50 = 0.49 ± 0.01 mg mL-1) than on JBU (IC50 = 0.54 ± 0.01 mg mL-1). Enzyme inhibitory kinetic analysis revealed that the inhibition type of DGE against HPU was slow-binding and anti-competitive, whereas it was slow-binding and mixed type on JBU. A further mechanism study indicated that the protective effect of sulfhydryl-containing compounds on enzyme activity was significantly better than that of inorganic compounds, indicating that the action site of DGE inhibition of enzyme was the sulfhydryl residue. The results of DTT reactivation experiments showed that the DGE-urease complex was reversible. Furthermore, molecular docking investigation showed that the main components of DGE interacted with sulfhydryl groups and Ni2+. In conclusion, DGE effectively inhibited the growth of H. pylori and the activity of its key virulence factor urease. And the in-depth study of the kinetic characteristics and the mechanism of action showed that the active site sulfhydryl group and Ni2+ might be the targets of urease inhibition by DGE. Our study may provide experimental evidence for the traditional application of dried ginger in the treatment of H. pylori-associated gastric diseases.
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Affiliation(s)
- Qiang Lu
- Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China
| | - Jiahao Wang
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China.
| | - Ying Tang
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China.
| | - Wenna Li
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China.
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, PR China
- Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi 563000, PR China
| | - Cailan Li
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China.
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, PR China
- Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi 563000, PR China
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Capasso L, De Masi L, Sirignano C, Maresca V, Basile A, Nebbioso A, Rigano D, Bontempo P. Epigallocatechin Gallate (EGCG): Pharmacological Properties, Biological Activities and Therapeutic Potential. Molecules 2025; 30:654. [PMID: 39942757 PMCID: PMC11821029 DOI: 10.3390/molecules30030654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 01/26/2025] [Accepted: 01/29/2025] [Indexed: 02/16/2025] Open
Abstract
Epigallocatechin gallate (EGCG), the predominant catechin in green tea, comprises approximately 50% of its total polyphenol content and has garnered widespread recognition for its significant therapeutic potential. As the principal bioactive component of Camellia sinensis, EGCG is celebrated for its potent antioxidant, anti-inflammatory, cardioprotective, and antitumor properties. The bioavailability and metabolism of EGCG within the gut microbiota underscore its systemic effects, as it is absorbed in the intestine, metabolized into bioactive compounds, and transported to target organs. This compound has been shown to influence key physiological pathways, particularly those related to lipid metabolism and inflammation, offering protective effects against a variety of diseases. EGCG's ability to modulate cell signaling pathways associated with oxidative stress, apoptosis, and immune regulation highlights its multifaceted role in health promotion. Emerging evidence underscores EGCG's therapeutic potential in preventing and managing a range of chronic conditions, including cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Given the growing prevalence of lifestyle-related diseases and the increasing interest in natural compounds, EGCG presents a promising avenue for novel therapeutic strategies. This review aims to summarize current knowledge on EGCG, emphasizing its critical role as a versatile natural bioactive agent with diverse clinical applications. Further exploration in both experimental and clinical settings is essential to fully unlock its therapeutic potential.
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Affiliation(s)
- Lucia Capasso
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (L.C.); (A.N.)
| | - Luigi De Masi
- National Research Council (CNR), Institute of Biosciences and BioResources (IBBR), Via Università 133, 80055 Portici, Italy;
| | - Carmina Sirignano
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy;
| | - Viviana Maresca
- Department of Life Science, Health, and Health Professions, Link Campus University, 00165 Rome, Italy;
| | - Adriana Basile
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy;
| | - Angela Nebbioso
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (L.C.); (A.N.)
| | - Daniela Rigano
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy;
| | - Paola Bontempo
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (L.C.); (A.N.)
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Wang J, Huan C, Lyu Q, Tian X, Liu Y, Ji G, Yan Z. Efficacy of composite bacterial deodorant constructed with Camellia sinensis and its in-situ deodorization mechanism on pig manure. WASTE MANAGEMENT (NEW YORK, N.Y.) 2025; 192:69-81. [PMID: 39615288 DOI: 10.1016/j.wasman.2024.11.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 11/19/2024] [Accepted: 11/24/2024] [Indexed: 12/10/2024]
Abstract
Here, we constructed a novel bacterial deodorant (BD) composed of Delftia tsuruhatensis, Paracoccus denitrificans, Pediococcus acidilactici, and Bacillus velezensis. The BD alone removed 64.84 % of NH3, 100 % of H2S, and 63.68 % of comprehensive odor (OU) during a five-day fermentation of pig manure. The effect was enhanced by introducing Camellia sinensis in the composite bacterial deodorant (CBD) treatment, with the removal efficiency (RE) of NH3 and OU being 88.68 % and 88.14 %, respectively. In prolonged trials, maximum RE of NH3, H2S and OU RE reached 90.16 %, 92.32 % and 100 % in CBD group. Bacterial composition of manure revealed that the abundance of odor-producing microbes (Kurthia, Solibacillus, Proteiniphilum and Acholeplasma) and potential pathogens decreased after CBD application. Functional prediction and correlation analyses indicated that the process of nitrification, denitrification and S/N assimilation were facilitated, while S/N mineralization and methanogenesis processes might be inhibited. This deodorant promoted the conversion of malodorous substances into non-odorous forms, establishing an efficient odor removal system in hoggery. Therefore, the bacterial deodorant compounded with C. sinensis has been shown to be an effective method for deodorizing pig farms. This approach will advance the livestock industry toward greener practices and environmental protection, contributing positively to the development of a sustainable agro-ecosystem.
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Affiliation(s)
- Jialing Wang
- CAS Key Laboratory of Environmental and Applied Microbiology, Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610213, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Chenchen Huan
- CAS Key Laboratory of Environmental and Applied Microbiology, Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610213, China
| | - Qingyang Lyu
- CAS Key Laboratory of Environmental and Applied Microbiology, Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610213, China
| | - Xueping Tian
- CAS Key Laboratory of Environmental and Applied Microbiology, Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610213, China
| | - Yang Liu
- CAS Key Laboratory of Environmental and Applied Microbiology, Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610213, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Gaosheng Ji
- CAS Key Laboratory of Environmental and Applied Microbiology, Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610213, China
| | - Zhiying Yan
- CAS Key Laboratory of Environmental and Applied Microbiology, Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610213, China; University of Chinese Academy of Sciences, Beijing 100049, China.
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Güzel-Akdemir Ö, Akdemir A. Urease inhibitors for the treatment of H. pylori. Expert Opin Ther Pat 2025; 35:17-30. [PMID: 39495126 DOI: 10.1080/13543776.2024.2423004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 09/16/2024] [Accepted: 10/16/2024] [Indexed: 11/05/2024]
Abstract
INTRODUCTION Helicobacter pylori infects almost half of the World population. Although many infected people are symptom free, the microorganism can still cause a variety of gastrointestinal disorders and gastric adenocarcinoma. It is considered a priority pathogen for the development of new antibiotics by the World Health Organisation (WHO). Many virulence factors of H. pylori have been described. This paper will on H. pylori Urease (HPU). AREA COVERED This paper will discuss the (patho)physiology and structure of HPU. In addition, urease inhibitors with known activity against the HPU or inhibitors that show H. pylori growth inhibition will be discussed. EXPERT OPINION Increase in selectivity, affinity and potency of HPU inhibitors can be achieved by the design of compounds that interact with distinct regions within the enzyme active site. Especially, covalent interactions seem promising as they clearly effect the dose requirement of the drug candidate.
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Affiliation(s)
- Özlen Güzel-Akdemir
- Department of Pharmaceutical Chemistry, Istanbul University, Faculty of Pharmacy, Beyazit/Istanbul, Turkey
| | - Atilla Akdemir
- Department of Pharmacology, Faculty of Pharmacy, Istinye University, Sariyer/Istanbul, Turkey
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Wang C, Yao M, Zhong H, Meena SS, Shu F, Nie S, Xie M. Natural foods resources and dietary ingredients for the amelioration of Helicobacter pylori infection. Front Med (Lausanne) 2023; 10:1324473. [PMID: 38131043 PMCID: PMC10734694 DOI: 10.3389/fmed.2023.1324473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 11/16/2023] [Indexed: 12/23/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a gastric-persistent pathogen that can cause peptic ulcer disease, gastric cancer, and mucosal-associated lymphoid tissue lymphoma. This pathogen is commonly treated with antibiotic-based triple or quadruple therapy. However, antibiotic therapy could result in the bacterial resistance, imbalance of gut microbiota, and damage to the liver and kidneys, etc. Therefore, there is an urgent need for alternative therapeutic strategies. Interestingly, natural food resources, like vegetables, fruits, spices, and edible herbs, have potent inhibitory effects on H. pylori. In this review, we systematically summarized these foods with supporting evidence from both animal and clinical studies. The results have indicated that natural foods may possess temporary inhibition effect on H. pylori rather than durable eradication, and may help to reduce H. pylori colonization, enhance the effect of antibiotics and modulate the host's immune response.
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Affiliation(s)
- Chengyuan Wang
- State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, Jiangxi, China
| | - Meixiang Yao
- Jiangzhong Dietary Therapy Technology Co. Ltd, Jiujiang, Jiangxi, China
| | - Hongguang Zhong
- Jiangzhong Dietary Therapy Technology Co. Ltd, Jiujiang, Jiangxi, China
| | - Stephene S. Meena
- Jiangzhong Cancer Research, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
| | - Fuxing Shu
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiangsu, China
| | - Shaoping Nie
- State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, Jiangxi, China
| | - Mingyong Xie
- State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, Jiangxi, China
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Wang C, Bai M, Sun Z, Yao N, Zhang A, Guo S, Asemi Z. Epigallocatechin-3-gallate and cancer: focus on the role of microRNAs. Cancer Cell Int 2023; 23:241. [PMID: 37838685 PMCID: PMC10576883 DOI: 10.1186/s12935-023-03081-8] [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: 07/26/2023] [Accepted: 09/21/2023] [Indexed: 10/16/2023] Open
Abstract
MicroRNAs (miRNAs) are a group of small non-coding RNAs that affect gene expression. The role of miRNAs in different types of cancers has been published and it was shown that several miRNAs are inappropriately expressed in different cancers. Among the mechanisms that can cause this lack of proper expression are epigenetics, chromosomal changes, polymorphisms or defects in processing proteins. Recent research shows that phytochemicals, including epigallocatechin-3-gallate (EGCG), exert important epigenetic-based anticancer effects such as pro-apoptotic or anti proliferative through miRNA gene silencing. Given that EGCG is able to modulate a variety of cancer-related process i.e., angiogenesis, proliferation, metastasis and apoptosis via targeting various miRNAs such as let-7, miR-16, and miR-210. The discovery of new miRNAs and the differences observed in their expression when exposed to EGCG provides evidence that targeting these miRNAs may be beneficial as a form of treatment. In this review, we aim to provide an overview, based on current knowledge, on how phytochemicals, including epigallocatechin-3-gallate, can be considered as potential miRNAs modulator to improve efficacy of current cancer treatments.
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Affiliation(s)
- Chunguang Wang
- The First Affiliated Hospital of Hebei North University, Zhang Jiakou, 075000, Hebei, China
| | - Meiling Bai
- Basic Medical College of Hebei North University, Zhang Jiakou, 075000, Hebei, China.
| | - Zhiguang Sun
- The First Affiliated Hospital of Hebei North University, Zhang Jiakou, 075000, Hebei, China
| | - Nan Yao
- The First Affiliated Hospital of Hebei North University, Zhang Jiakou, 075000, Hebei, China
| | - Aiting Zhang
- The First Affiliated Hospital of Hebei North University, Zhang Jiakou, 075000, Hebei, China
| | - Shengyu Guo
- The First Affiliated Hospital of Hebei North University, Zhang Jiakou, 075000, Hebei, China
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran.
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Maślanka M, Tabor W, Krzyżek P, Grabowiecka A, Berlicki Ł, Mucha A. Inhibitory activity of catecholic phosphonic and phosphinic acids against Helicobacter pylori ureolysis. Eur J Med Chem 2023; 257:115528. [PMID: 37290184 DOI: 10.1016/j.ejmech.2023.115528] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/22/2023] [Accepted: 05/25/2023] [Indexed: 06/10/2023]
Abstract
Catechols have been reported to be potent covalent inhibitors of ureases, and they exhibit activity by modifying cysteine residues at the entrance to enzymatic active sites. Following these principles, we designed and synthesized novel catecholic derivatives that contained carboxylate and phosphonic/phosphinic functionalities and assumed expanded specific interactions. When studying the chemical stability of the molecules, we found that their intrinsic acidity catalyzes spontaneous esterification/hydrolysis reactions in methanol or water solutions, respectively. Regarding biological activity, the most promising compound, 2-(3,4-dihydroxyphenyl)-3-phosphonopropionic acid (15), exhibited significant anti-urease potential (Ki = 2.36 μM, Sporosarcinia pasteurii urease), which was reflected in the antiureolytic effect in live Helicobacter pylori cells at a submicromolar concentration (IC50 = 0.75 μM). As illustrated by molecular modeling, this compound was bound in the active site of urease through a set of concerted electrostatic and hydrogen bond interactions. The antiureolytic activity of catecholic phosphonic acids could be specific because these compounds were chemically inert and not cytotoxic to eukaryotic cells.
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Affiliation(s)
- Marta Maślanka
- Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland
| | - Wojciech Tabor
- Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland
| | - Paweł Krzyżek
- Department of Microbiology, Faculty of Medicine, Wrocław Medical University, Wybrzeże L. Pasteura 1, 50-367, Wrocław, Poland
| | - Agnieszka Grabowiecka
- Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland
| | - Łukasz Berlicki
- Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland
| | - Artur Mucha
- Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
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Al-Rooqi MM, Mughal EU, Raja QA, Hussein EM, Naeem N, Sadiq A, Asghar BH, Moussa Z, Ahmed SA. Flavonoids and related privileged scaffolds as potential urease inhibitors: a review. RSC Adv 2023; 13:3210-3233. [PMID: 36756398 PMCID: PMC9869662 DOI: 10.1039/d2ra08284e] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 01/16/2023] [Indexed: 01/25/2023] Open
Abstract
Infections caused by bacteria are a significant issue on a global scale, and imperative action is required to discover novel or improved therapeutic agents. Flavonoids are a class of plant-derived compounds that have a variety of potentially useful bioactivities. These activities include immediate antimicrobial properties, synergistic effect with antimicrobials, ferocious repression of pathogenicity, anti-urease activity etc. This review summarizes current studies concerning anti-urease actions of flavonoids as well as structural-activity correlation investigations of the flavonoid core structure. It is possible that if researchers investigate the many structural changes that may be made in flavonoid rings, they'll be able to build up novel compounds that have powerful and effective anti-urease properties.
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Affiliation(s)
- Munirah M Al-Rooqi
- Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University 21955 Makkah Saudi Arabia
| | | | | | - Essam M Hussein
- Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University 21955 Makkah Saudi Arabia
- Chemistry Department, Faculty of Science, Assiut University 71516 Assiut Egypt
| | - Nafeesa Naeem
- Department of Chemistry, University of Gujrat Gujrat-50700 Pakistan
| | - Amina Sadiq
- Department of Chemistry, Government College Women University Sialkot-51300 Pakistan
| | - Basim H Asghar
- Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University 21955 Makkah Saudi Arabia
| | - Ziad Moussa
- Department of Chemistry, College of Science, United Arab Emirates University P.O. Box 15551, Al Ain Abu Dhabi United Arab Emirates
| | - Saleh A Ahmed
- Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University 21955 Makkah Saudi Arabia
- Chemistry Department, Faculty of Science, Assiut University 71516 Assiut Egypt
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12
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Lu Q, Zhang Z, Xu Y, Chen Y, Li C. Sanguinarine, a major alkaloid from Zanthoxylum nitidum (Roxb.) DC., inhibits urease of Helicobacter pylori and jack bean: Susceptibility and mechanism. JOURNAL OF ETHNOPHARMACOLOGY 2022; 295:115388. [PMID: 35577159 DOI: 10.1016/j.jep.2022.115388] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 05/01/2022] [Accepted: 05/11/2022] [Indexed: 06/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Zanthoxylum nitidum (Roxb.) DC. (Z. nitidum) is a traditional Chinese medicine and mainly adopted to treat gastric ulcer, gastritis and stomach cancer. Sanguinarine (SNG), a natural alkaloid isolated from Z. nitidum, possesses significant anti-Helicobacter pylori and gastric protection effects. However, the underlying mechanism is sparsely elucidated. AIM OF THIS STUDY The present study aims to explore the inhibition effect, kinetics and potential mechanism of SNG against H. pylori urease (HPU) and jack bean urease (JBU). MATERIALS AND METHODS The improved spectrophotometric berthelot method was applied to estimate the inhibitory effect of SNG against HPU and JBU. The Lineweaver-Burk plots were adopted for investigating the inhibitory pattern in enzymatic kinetics. Sulfydryl-containing compounds and competitive active-site Ni2+ binding depressors were used for mechanism research. RESULTS SNG remarkably suppressed the activities of HPU and JBU in concentration-and time-dependent mode with IC50 of 0.48 ± 0.14 mM and 0.11 ± 0.02 mM, respectively, in comparison with urease retardant acetohydroxamic acid (0.06 ± 0.01 mM for HPU and 0.03 ± 0.00 mM for JBU, respectively). Kinetic analysis demonstrated that the inhibition of SNG against HPU and JBU were separately characterized by slow-binding, mixed-type and slow-binding, non-competitive type. Addition of sulfydryl-containing reagents (dithiothreitol, glutathione and L-cysteine) and competitive Ni2+ binding restrainers (boric acid and sodium fluoride) significantly abrogated the urease inhibitory effect of SNG, suggesting the significant role of the thiols and Ni2+ for the urease inhibition by SNG. By contrast, interaction with thiol groups possibly contributed to the repression of SNG on JBU. Furthermore, the urease suppression was proved to be partially reversible since the SNG-blocked enzyme could be partly reactivated by glutathione. CONCLUSION SNG could observably inhibit H. pylori urease targeting the thiols and Ni2+, which indicated that SNG was a new urease suppressant with great promise. The present research also provided scientific evidence for the application of SNG and Z. nitidum treating H. pylori-associated gastrointestinal diseases.
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Affiliation(s)
- Qiang Lu
- Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai, 519041, PR China
| | - Zhenshan Zhang
- Analysis & Test Center, Chinese Academy of Tropical Agricultural Sciences, Haikou, 571101, PR China
| | - Yifei Xu
- Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, 518005, PR China
| | - Yujia Chen
- Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai, 519041, PR China
| | - Cailan Li
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai, 519041, PR China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563000, PR China.
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13
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Role of Plant-Derived Active Constituents in Cancer Treatment and Their Mechanisms of Action. Cells 2022; 11:cells11081326. [PMID: 35456005 PMCID: PMC9031068 DOI: 10.3390/cells11081326] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 03/31/2022] [Accepted: 04/11/2022] [Indexed: 02/07/2023] Open
Abstract
Despite significant technological advancements in conventional therapies, cancer remains one of the main causes of death worldwide. Although substantial progress has been made in the control and treatment of cancer, several limitations still exist, and there is scope for further advancements. Several adverse effects are associated with modern chemotherapy that hinder cancer treatment and lead to other critical disorders. Since ancient times, plant-based medicines have been employed in clinical practice and have yielded good results with few side effects. The modern research system and advanced screening techniques for plants’ bioactive constituents have enabled phytochemical discovery for the prevention and treatment of challenging diseases such as cancer. Phytochemicals such as vincristine, vinblastine, paclitaxel, curcumin, colchicine, and lycopene have shown promising anticancer effects. Discovery of more plant-derived bioactive compounds should be encouraged via the exploitation of advanced and innovative research techniques, to prevent and treat advanced-stage cancers without causing significant adverse effects. This review highlights numerous plant-derived bioactive molecules that have shown potential as anticancer agents and their probable mechanisms of action and provides an overview of in vitro, in vivo and clinical trial studies on anticancer phytochemicals.
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Yang W, Feng Q, Peng Z, Wang G. An overview on the synthetic urease inhibitors with structure-activity relationship and molecular docking. Eur J Med Chem 2022; 234:114273. [PMID: 35305460 DOI: 10.1016/j.ejmech.2022.114273] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 03/04/2022] [Accepted: 03/08/2022] [Indexed: 01/06/2023]
Abstract
Urease is a kind of enzyme which could be found in various bacteria, fungi, plants, and algae, which can quickly catalyze the hydrolysis of urea into ammonia and carbon dioxide. With the ammonia concentration increasing, the activity of Helicobacter pylori has got an obvious enhancement and leads to mucosal damage in the stomach, gastroduodenal infection, peptic ulcers, and gastric cancer. The infectious diseases caused by Helicobacter pylori can be controlled to a certain extent by inhibiting urease activity with urease inhibitors. Hence, studies of urease inhibitors have attracted great attention all over the world and a variety of effective urease inhibitors have been synthesized in recent years. In this review, we will draw summaries for these inhibitors including urease inhibitory activity, inhibition kinetics, structure-activity relationship, and molecular docking. The collected information is expected to provide rational guidance and effective strategy to develop novel, potent, and safe urease inhibitors for better practical applications in the future.
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Affiliation(s)
- Wei Yang
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China; Teaching and Research Section of Natural Medicinal Chemistry, School of Pharmacy, Guizhou Medical University, Guiyang, China
| | - Qianqian Feng
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China; Teaching and Research Section of Natural Medicinal Chemistry, School of Pharmacy, Guizhou Medical University, Guiyang, China
| | - Zhiyun Peng
- Office of Drug Clinical Trial Institutions, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
| | - Guangcheng Wang
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China; Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, China.
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15
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Abou Baker DH. An ethnopharmacological review on the therapeutical properties of flavonoids and their mechanisms of actions: A comprehensive review based on up to date knowledge. Toxicol Rep 2022; 9:445-469. [PMID: 35340621 PMCID: PMC8943219 DOI: 10.1016/j.toxrep.2022.03.011] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 03/03/2022] [Accepted: 03/04/2022] [Indexed: 12/11/2022] Open
Abstract
Flavonoids -a class of low molecular weight secondary metabolites- are ubiquitous and cornucopia throughout the plant kingdom. Structurally, the main structure consists of C6-C3-C6 rings with different substitution patterns so that many sub-classes are obtained, for example: flavonols, flavonolignans, flavonoid glycosides, flavans, anthocyanidins, aurones, anthocyanidins, flavones, neoflavonoids, chalcones, isoflavones, flavones and flavanones. Flavonoids are evaluated to have drug like nature since they possess different therapeutic activities, and can act as cardioprotective, antiviral, antidiabetic, anti-inflammatory, antibacterial, anticancer, and also work against Alzheimer's disease and others. However, information on the relationship between their structure and biological activity is scarce. Therefore, the present review tries to summarize all the therapeutic activities of flavonoids, their mechanisms of action and the structure activity relationship.
Latest updated ethnopharmacological review of the therapeutic effects of flavonoids. Flavonoids are attracting attention because of their therapeutic properties. Flavonoids are valuable candidates for drug development against many dangerous diseases. This overview summarizes the most important therapeutic effect and mechanism of action of flavonoids. General knowledge about the structure activity relationship of flavonoids is summarized. Substitution of chemical groups in the structure of flavonoids can significantly change their biological and chemical properties. The chemical properties of the basic flavonoid structure should be considered in a drug-based structural program.
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Synthesis and in vitro urease inhibitory activity of 5-nitrofuran-2-yl-thiadiazole linked to different cyclohexyl-2-(phenylamino)acetamides, in silico and kinetic studies. Bioorg Chem 2022; 120:105592. [DOI: 10.1016/j.bioorg.2021.105592] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 12/08/2021] [Accepted: 12/13/2021] [Indexed: 02/05/2023]
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17
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Mamidala R, Bhimathati SRS, Vema A. Discovery of Novel Dihydropyrimidine and hydroxamic acid hybrids as potent Helicobacter pylori Urease inhibitors. Bioorg Chem 2021; 114:105010. [PMID: 34102519 DOI: 10.1016/j.bioorg.2021.105010] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 05/19/2021] [Accepted: 05/20/2021] [Indexed: 11/25/2022]
Abstract
Two novel series of Dihydropyrimidine-hydroxamic acid hybrids (4a-4l and 5a-5l) were designed, synthesized and evaluated for in vitro Helicobacter pylori urease inhibition. In vitro enzyme inhibition screening led to the discovery of three potent urease inhibitors 2-[[4-(4-hydroxy phenyl)-6-oxo-1,6-dihydropyrimidine-2-yl]-amino]-N-hydroxy acetamide (4g), 2-[[4-(4-chloro phenyl)-6-oxo-1,6-dihydropyrimidine-2-yl]-amino]-N-hydroxy acetamide (4b) and 3-[[4-(3-methoxy phenyl)-6-oxo-1,6-dihydropyrimidine-2-yl]-amino]-N-hydroxy propanamide (5l). Compound 4g showed excellent urease inhibition with IC50 value of 14 ± 1 nM, indicated by its strong interactions with both metallic Ni++ ions, Gly279, His221, Ala365, Asp362, Asn168, Arg338 and His322 residues of the active site of urease. Further, compounds 4b and 5l displayed very good activity with IC50 value of 0.082 ± 0.004 µM and 0.14 ± 0.013 µM respectively compared to standard Acetohydroxamic acid (IC50 - 27.4 ± 1.2 µM). Kinetic studies revealed that a mixed inhibition with both competitive and non-competitive aspects is involved in the urease inhibition mechanism. The in vitro urease inhibition results were supported by molecular docking studies. Collectively, this study indicates that 4g could be considered as promising lead molecule that can be further developed as a potent drug molecule for the treatment of Helicobacter pylori caused gastritis for further studies.
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Affiliation(s)
- Ravinder Mamidala
- Department of Medicinal Chemistry, St. Peter's Institute of Pharmaceutical Sciences, Hanamkonda, Warangal, Telangana 506001, India; Department of Pharmaceutical Chemistry, Institute of Science and Technology, Jawaharlal Nehru Technological University, Hyderabad, Telangana 500085, India
| | - Solomon Raj S Bhimathati
- Department of Pharmacology, Gland Institute of Pharmaceutical Sciences, Medak, Telangana 502220, India
| | - Aparna Vema
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
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18
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Mayyas A, Abu-Sini M, Amr R, Akasheh RT, Zalloum W, Khdair A, Hamad I, Aburjai T, Darwish RM, Abu-Qatouseh L. Novel in vitro and in vivo anti- Helicobacter pylori effects of pomegranate peel ethanol extract. Vet World 2021; 14:120-128. [PMID: 33642795 PMCID: PMC7896906 DOI: 10.14202/vetworld.2021.120-128] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 12/01/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND AND AIM Interest in plants with antimicrobial properties has been revived due to emerging problems associated with using antibiotics to eradicate Helicobacter pylori. Accordingly, this study aims to assess the antibacterial effects of Punica granatum and the possible synergistic effect of its extract along with metronidazole against H. pylori. MATERIALS AND METHODS Pomegranate peel ethanol extracts (PPEE) was tested against a control strain of H. pylori (NCTC 11916) in vitro and in vivo in female Wistar rats. Moreover, the synergistic effect of PPEE in combination with metronidazole was tested in vitro. RESULTS The PPEE exhibited a remarkable activity against H. pylori with a minimum inhibitory concentration (MIC) of 0.156 mg/mL. Furthermore, the extract exhibited a pronounced urease inhibitory activity (IC50 ~6 mg/mL) against the tested strain. A synergistic effect between PPEE and metronidazole was also observed (fractional inhibitory concentrations <0.5). Oral treatment of rats with PPEE for 8 days produced a significant reduction in H. pylori gastritis and a significant decrease in both lymphocytic and positive chronicity. CONCLUSION Pomegranate extract is probably safe and represents a potential alternative and complementary therapy for reducing H. pylori associated with gastric ulcers.
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Affiliation(s)
- Amal Mayyas
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, 11914 Amman, Jordan
- Department of Pharmacy, Faculty of Health Sciences, American University of Madaba, 11821 Madaba, Jordan
| | - Mohammad Abu-Sini
- Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan
| | - Rula Amr
- Department of Pharmacy, Faculty of Health Sciences, American University of Madaba, 11821 Madaba, Jordan
| | - Rand T. Akasheh
- Department of Pharmacy, Faculty of Health Sciences, American University of Madaba, 11821 Madaba, Jordan
| | - Waleed Zalloum
- Department of Pharmacy, Faculty of Health Sciences, American University of Madaba, 11821 Madaba, Jordan
| | - Ayman Khdair
- Department of Pharmacy, Faculty of Health Sciences, American University of Madaba, 11821 Madaba, Jordan
| | - Islam Hamad
- Department of Pharmacy, Faculty of Health Sciences, American University of Madaba, 11821 Madaba, Jordan
| | - Talal Aburjai
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, 11914 Amman, Jordan
| | - Rula M. Darwish
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, 11914 Amman, Jordan
| | - Luay Abu-Qatouseh
- Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy, University of Petra, 961343 Amman, Jordan
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19
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Baker DA. Plants against Helicobacter pylori to combat resistance: An ethnopharmacological review. ACTA ACUST UNITED AC 2020; 26:e00470. [PMID: 32477900 PMCID: PMC7248673 DOI: 10.1016/j.btre.2020.e00470] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 03/02/2020] [Accepted: 05/12/2020] [Indexed: 12/22/2022]
Abstract
Worldwide, Helicobacter pylori (H. pylori) is regarded as the major etiological agent of peptic ulcer and gastric carcinoma. Claiming about 50 percent of the world population is infected with H. pylori while therapies for its eradication have failed because of many reasons including the acquired resistance against its antibiotics. Hence, the need to find new anti-H.pylori medications has become a hotspot with the urge of searching for alternative, more potent and safer inhibitors. In the recent drug technology scenario, medicinal plants are suggested as repositories for novel synthetic substances. Hitherto, is considered as ecofriendly, simple, more secure, easy, quick, and less toxic traditional treatment technique. This review is to highlight the anti-H. pylori medicinal plants, secondary metabolites and their mode of action with the aim of documenting such plants before they are effected by cultures and traditions that is expected as necessity.
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Affiliation(s)
- Doha Abou Baker
- Medicinal and Aromatic Plants Dept., Pharmaceutical and Drug Industries Division, National Research Centre, Cairo, Egypt
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20
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Lu Q, Li C, Wu G. Insight into the inhibitory effects of Zanthoxylum nitidum against Helicobacter pylori urease and jack bean urease: Kinetics and mechanism. JOURNAL OF ETHNOPHARMACOLOGY 2020; 249:112419. [PMID: 31759110 DOI: 10.1016/j.jep.2019.112419] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 11/18/2019] [Accepted: 11/19/2019] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Zanthoxylum nitidum (Roxb.) DC. is a traditional Chinese medicine characterised by anti-inflammatory and anti-Helicobacter pylori, which is widely used to treat H. pylori-induced gastric disease in China. However, the underlying mechanism related to its anti-H. pylori activity remains unclear. Urease plays a crucial role in the colonisation and survival of H. pylori. AIM OF THE STUDY The root aqueous extract of Z. nitidum against H. pylori urease (HPU) and jack bean urease (JBU) was investigated to illuminate the inhibitory potency, kinetics and potential mechanism. MATERIALS AND METHODS Z. nitidum components were determined by UPLC. The enzyme inhibitory effects of Z. nitidum were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. Urease inhibition kinetics were determined by Lineweaver-Burk plots. Sulfhydryl group reagents and Ni2+-binding inhibitors were used in the mechanism study. Moreover, the molecular docking technique was used to investigate the binding conformations of the main compounds of Z. nitidum on Urease. RESULTS According to UPLC results, the major components of Z. nitidum were magnoflorine, sanguinarine, nitidine chloride, chelerythrine, skimmianine and L-Sesamin. Z. nitidum has higher enzyme inhibitory activity on HPU (IC50 = 1.29 ± 0.10 mg/mL) than on JBU (IC50 = 2.04 ± 0.27 mg/mL). Enzyme inhibitory kinetic analysis revealed that the type of Z. nitidum inhibition against HPU was a slow-binding and mixed-type, whereas a slow-binding and non-competitive type inhibited JBU. Further mechanism study indicated that the active site of sulfhydryl group might be the target of inhibition by Z. nitidum. The molecular docking study indicated that the above six main components of Z. nitidum exhibited stronger affinity to HPU than to JBU through interacting with the key amino acid residues located on the mobile flap or interacting with the active site Ni2+. Results indicated that these components are potential active ingredients directed against urease. CONCLUSIONS Z. nitidum inactivated urease in a concentration-dependent manner through slow-binding inhibition and binding to the urease active site sulfhydryl group. Our investigation might provide experimental evidence for the traditional application of Z. nitidum in the treatment of H. pylori-associated gastric disorders.
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Affiliation(s)
- Qiang Lu
- Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai, 519041, PR China.
| | - Cailan Li
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai, 519041, PR China.
| | - Guosong Wu
- Pharmacy Department, Guangzhou the People's Hospital of Baiyun District, Guangzhou, 510500, PR China.
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21
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Kataria R, Khatkar A. Lead Molecules for Targeted Urease Inhibition: An Updated Review from 2010 -2018. Curr Protein Pept Sci 2020; 20:1158-1188. [PMID: 30894105 DOI: 10.2174/1389203720666190320170215] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 02/01/2019] [Accepted: 03/15/2019] [Indexed: 12/14/2022]
Abstract
The field of enzyme inhibition is a tremendous and quickly growing territory of research. Urease a nickel containing metalloenzyme found in bacteria, algae, fungi, and plants brings hydrolysis of urea and plays important role in environmental nitrogen cycle. Apart from this it was found to be responsible for many pathological conditions due to its presence in many microorganisms such as H. Pylori, a ureolytic bacteria having urease which elevates pH of gastric medium by hydrolyzing urea present in alimentary canal and help the bacteria to colonize and spread infection. Due to the infections caused by the various bacterial ureases such as Bacillus pasteurii, Brucella abortus, H. pylori, H. mustelae, Klebsiella aerogenes, Klebsiella tuberculosis, Mycobacterium tuberculosis, Pseudomonas putida, Sporosarcina pasteurii and Yersinia enterocolitica, it has been the current topic of today's research. About a wide range of compounds from the exhaustive literature survey has been discussed in this review which is enveloped into two expansive classes, as Inhibitors from synthetic origin and Inhibitors from natural origin. Moreover active site details of enzyme, mechanism of catalysis of substrate by enzyme, uses of plant urease and its pathogenic behavior has been included in the current review. So, overall, this review article diagrams the current landscape of the developments in the improvements in the thriving field of urease inhibitory movement in medicinal chemistry from year 2010 to 2018, with an emphasis on mechanism of action of inhibitors that may be used for more development of recent and strong urease inhibitors and open up new doors for assist examinations in a standout amongst the most lively and promising regions of research.
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Affiliation(s)
- Ritu Kataria
- International Institute of Pharmaceutical Sciences, Sonepat, Haryana, India
| | - Anurag Khatkar
- Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India
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Zou J, Xiao YQ, Cheng YF, Ren XY, Li SW, Gang D. Investigation of Helicobacter pylori Infection and Its Related Factors in the Tianjin Binhai Area, China. Jundishapur J Microbiol 2019; 12. [DOI: 10.5812/jjm.94845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025] Open
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Liu X, Zhang M, Li Z, Zhang C, Wan C, Zhang Y, Lee DJ. Inhibition of urease activity by humic acid extracted from sludge fermentation liquid. BIORESOURCE TECHNOLOGY 2019; 290:121767. [PMID: 31302466 DOI: 10.1016/j.biortech.2019.121767] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 07/02/2019] [Accepted: 07/04/2019] [Indexed: 06/10/2023]
Abstract
This study achieved effective extraction of humic acid from sludge fermentation liquid, and the inhibition of urease activity by the extract were investigated in the urea decomposition. The addition of extract could remarkably inhibit urease activity and extend the releasing time of ammonia nitrogen. The interaction between the extract and urease took times, and the inhibition was irreversible. The results of fluorescence analysis revealed that the inhibition of urease activity was correlated to the amount of humic acid extracted. The mechanisms of inhibition were proposed that the functional groups of humic acid might interact with the thiol group of urease and formed a larger particle size of complex to inhibit the activity of urease. The extraction of humic acid from sludge fermentation liquid can not only recover the resource from the fermentation liquid, but also provide a potential urease inhibitor for the sustained-release effect of the soil organic nitrogen fertilizer.
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Affiliation(s)
- Xiang Liu
- Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
| | - Min Zhang
- Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
| | - Zhengwen Li
- Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
| | - Chen Zhang
- Shanghai Municipal Engineering Design General Institute, Shanghai 200092, China
| | - Chunli Wan
- Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China.
| | - Yi Zhang
- Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
| | - Duu-Jong Lee
- Department of Chemical Engineering, National Taiwan University, Taipei 106, Taiwan; Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan
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Lee MH, Yang JY, Cho Y, Woo HJ, Kwon HJ, Kim DH, Park M, Moon C, Yeon MJ, Kim HW, Seo WD, Kim SH, Kim JB. Inhibitory Effects of Menadione on Helicobacter pylori Growth and Helicobacter pylori-Induced Inflammation via NF-κB Inhibition. Int J Mol Sci 2019; 20:ijms20051169. [PMID: 30866458 PMCID: PMC6429389 DOI: 10.3390/ijms20051169] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 03/01/2019] [Accepted: 03/04/2019] [Indexed: 12/19/2022] Open
Abstract
H. pylori is classified as a group I carcinogen by WHO because of its involvement in gastric cancer development. Several reports have suggested anti-bacterial effects of menadione, although the effect of menadione on major virulence factors of H. pylori and H. pylori-induced inflammation is yet to be elucidated. In this study, therefore, we demonstrated that menadione has anti-H. pylori and anti-inflammatory effects. Menadione inhibited growth of H. pylori reference strains and clinical isolates. Menadione reduced expression of vacA in H. pylori, and translocation of VacA protein into AGS (gastric adenocarcinoma cell) was also decreased by menadione treatment. This result was concordant with decreased apoptosis in AGS cells infected with H. pylori. Moreover, cytotoxin-associated protein A (CagA) translocation into H. pylori-infected AGS cells was also decreased by menadione. Menadione inhibited expression of several type IV secretion system (T4SS) components, including virB2, virB7, virB8, and virB10, that are responsible for translocation of CagA into host cells. In particular, menadione inhibited nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) activation and thereby reduced expression of the proinflammatory cytokines such as IL-1β, IL-6, IL-8, and TNF-α in AGS as well as in THP-1 (monocytic leukemia cell) cell lines. Collectively, these results suggest the anti-bacterial and anti-inflammatory effects of menadione against H. pylori.
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Affiliation(s)
- Min Ho Lee
- Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Korea.
- Forensic DNA Division, National Forensic Service, Wonju 26460, Korea.
| | - Ji Yeong Yang
- Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Korea.
| | - Yoonjung Cho
- Forensic DNA Division, National Forensic Service, Wonju 26460, Korea.
| | - Hyun Jun Woo
- Department of Clinical Laboratory Science, College of Medical Sciences, Daegu Haany University, Gyeongsan 38610, Korea.
| | - Hye Jin Kwon
- Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Korea.
| | - Do Hyun Kim
- Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Korea.
| | - Min Park
- Department of Biomedical Laboratory Science, Daekyeung University, Gyeongsan 38547, Korea.
| | - Cheol Moon
- Department of Clinical Laboratory Science, Semyung University, Jecheon 27136, Korea.
| | - Min Ji Yeon
- Natural Products Research Center, Korea Institute of Science and Technology (KIST) Gangneung 25451, Korea.
| | - Hyun Woo Kim
- Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Korea.
| | - Woo-Duck Seo
- National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju-Gun 55365, Korea.
| | - Sa-Hyun Kim
- Department of Clinical Laboratory Science, Semyung University, Jecheon 27136, Korea.
| | - Jong-Bae Kim
- Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Korea.
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Aimasso U, D'onofrio V, D'eusebio C, Devecchi A, Pira C, Merlo FD, De Francesco A. Helicobacter pylori and nutrition: a bidirectional communication. MINERVA GASTROENTERO 2019; 65:116-129. [PMID: 30759976 DOI: 10.23736/s1121-421x.19.02568-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Helicobacter pylori (HP) is a gram-negative flagellated pathogen acid-resistant bacterium; it belongs to the order Campylobacterales that is wide spread all over the world, infecting more than 50% of the world population. HP infection is etiologically associated with non-atrophic and atrophic gastritis, peptic ulcer and with 3 to 6-fold increased relative risk for developing gastric adenocarcinoma and mucosa-associated lymphoid tissue (MA LT) lymphoma. For this reason HP is recognized by the World Health Organization as a Class I human carcinogen. In the last years a lot of studies clarified the role of this pathogen in nutrition and metabolism; particularly, it has been shown that it is able to induce malabsorption of several nutrients like iron, cobalamin, vitamin C and vitamin E, with strong consequences on nutritional status. Interesting, this bacterium is able to produce different biological effects on hormones like ghrelin and leptin controlling both appetite and growth, mostly depending on the time of acquisition of the infection and of its treatment. In this review, the authors focused their attention on nutritional effects of HP infection and particularly on the role that diet, food, plants and specific nutrients can play in its treatment, considering that HP eradication rates, with standard triple-therapy, have fallen to a low level in the last years.
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Affiliation(s)
- Umberto Aimasso
- Unit of Dietetics and Clinical Nutrition, Città della Salute e della Scienza, Turin, Italy -
| | - Valentina D'onofrio
- Unit of Dietetics and Clinical Nutrition, Città della Salute e della Scienza, Turin, Italy
| | - Chiara D'eusebio
- Unit of Dietetics and Clinical Nutrition, Città della Salute e della Scienza, Turin, Italy
| | - Andrea Devecchi
- Unit of Dietetics and Clinical Nutrition, Città della Salute e della Scienza, Turin, Italy
| | - Costanza Pira
- Unit of Dietetics and Clinical Nutrition, Città della Salute e della Scienza, Turin, Italy
| | - Fabio D Merlo
- Unit of Dietetics and Clinical Nutrition, Città della Salute e della Scienza, Turin, Italy
| | - Antonella De Francesco
- Unit of Dietetics and Clinical Nutrition, Città della Salute e della Scienza, Turin, Italy
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Kuna L, Jakab J, Smolic R, Raguz-Lucic N, Vcev A, Smolic M. Peptic Ulcer Disease: A Brief Review of Conventional Therapy and Herbal Treatment Options. J Clin Med 2019; 8:179. [PMID: 30717467 PMCID: PMC6406303 DOI: 10.3390/jcm8020179] [Citation(s) in RCA: 150] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Revised: 01/30/2019] [Accepted: 01/31/2019] [Indexed: 02/06/2023] Open
Abstract
Peptic ulcer is a chronic disease affecting up to 10% of the world's population. The formation of peptic ulcers depends on the presence of gastric juice pH and the decrease in mucosal defenses. Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) infection are the two major factors disrupting the mucosal resistance to injury. Conventional treatments of peptic ulcers, such as proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists, have demonstrated adverse effects, relapses, and various drug interactions. On the other hand, medicinal plants and their chemical compounds are useful in the prevention and treatment of numerous diseases. Hence, this review presents common medicinal plants that may be used for the treatment or prevention of peptic ulcers.
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Affiliation(s)
- Lucija Kuna
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
| | - Jelena Jakab
- Department of Pathophysiology and Physiology with Immunology, Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
- Department of Internal Medicine, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
| | - Robert Smolic
- Department of Pathophysiology and Physiology with Immunology, Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
- Department of Pharmacology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
- Department of Internal Medicine, University Hospital Osijek, 31000 Osijek, Croatia.
| | - Nikola Raguz-Lucic
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
| | - Aleksandar Vcev
- Department of Pathophysiology and Physiology with Immunology, Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
- Department of Internal Medicine, University Hospital Osijek, 31000 Osijek, Croatia.
| | - Martina Smolic
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
- Department of Pharmacology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
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Li C, Huang P, Wong K, Xu Y, Tan L, Chen H, Lu Q, Luo C, Tam C, Zhu L, Su Z, Xie J. Coptisine-induced inhibition of Helicobacter pylori: elucidation of specific mechanisms by probing urease active site and its maturation process. J Enzyme Inhib Med Chem 2018; 33:1362-1375. [PMID: 30191728 PMCID: PMC6136390 DOI: 10.1080/14756366.2018.1501044] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
In this study, we examined the anti-Helicobactor pylori effects of the main protoberberine-type alkaloids in Rhizoma Coptidis. Coptisine exerted varying antibacterial and bactericidal effects against three standard H. pylori strains and eleven clinical isolates, including four drug-resistant strains, with minimum inhibitory concentrations ranging from 25 to 50 μg/mL and minimal bactericidal concentrations ranging from 37.5 to 125 μg/mL. Coptisine’s anti-H. pylori effects derived from specific inhibition of urease in vivo. In vitro, coptisine inactivated urease in a concentration-dependent manner through slow-binding inhibition and involved binding to the urease active site sulfhydryl group. Coptisine inhibition of H. pylori urease (HPU) was mixed type, while inhibition of jack bean urease was non-competitive. Importantly, coptisine also inhibited HPU by binding to its nickel metallocentre. Besides, coptisine interfered with urease maturation by inhibiting activity of prototypical urease accessory protein UreG and formation of UreG dimers and by promoting dissociation of nickel from UreG dimers. These findings demonstrate that coptisine inhibits urease activity by targeting its active site and inhibiting its maturation, thereby effectively inhibiting H. pylori. Coptisine may thus be an effective anti-H. pylori agent.
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Affiliation(s)
- Cailan Li
- a Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine , Guangzhou University of Chinese Medicine , Guangzhou , P. R. China
| | - Ping Huang
- b School of Pharmaceutical Sciences , Guangzhou University of Chinese Medicine , Guangzhou , P. R. China
| | - Kambo Wong
- c School of Life Sciences , Center for Protein Science and Crystallography, The Chinese University of Hong Kong , P. R. China
| | - Yifei Xu
- b School of Pharmaceutical Sciences , Guangzhou University of Chinese Medicine , Guangzhou , P. R. China
| | - Lihua Tan
- a Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine , Guangzhou University of Chinese Medicine , Guangzhou , P. R. China
| | - Hanbin Chen
- d The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine , Guangzhou , P. R. China
| | - Qiang Lu
- e Key Laboratory of Chinese Medicinal Resource from Lingnan, Ministry of Education and Research Center of Chinese Herbal Resource Science and Engineering , Guangzhou University of Chinese Medicine , Guangzhou , P. R. China
| | - Chaodan Luo
- a Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine , Guangzhou University of Chinese Medicine , Guangzhou , P. R. China
| | - Chunlai Tam
- c School of Life Sciences , Center for Protein Science and Crystallography, The Chinese University of Hong Kong , P. R. China
| | - Lixiang Zhu
- b School of Pharmaceutical Sciences , Guangzhou University of Chinese Medicine , Guangzhou , P. R. China
| | - Ziren Su
- a Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine , Guangzhou University of Chinese Medicine , Guangzhou , P. R. China
| | - Jianhui Xie
- f Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome , The Second Affiliated Hospital, Guangzhou University of Chinese Medicine , Guangzhou , P. R. China
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Kappaun K, Piovesan AR, Carlini CR, Ligabue-Braun R. Ureases: Historical aspects, catalytic, and non-catalytic properties - A review. J Adv Res 2018; 13:3-17. [PMID: 30094078 PMCID: PMC6077230 DOI: 10.1016/j.jare.2018.05.010] [Citation(s) in RCA: 122] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 05/22/2018] [Accepted: 05/24/2018] [Indexed: 12/11/2022] Open
Abstract
Urease (urea amidohydrolase, EC 3.5.1.5) is a nickel-containing enzyme produced by plants, fungi, and bacteria that catalyzes the hydrolysis of urea into ammonia and carbamate. Urease is of historical importance in Biochemistry as it was the first enzyme ever to be crystallized (1926). Finding nickel in urease's active site (1975) was the first indication of a biological role for this metal. In this review, historical and structural features, kinetics aspects, activation of the metallocenter and inhibitors of the urea hydrolyzing activity of ureases are discussed. The review also deals with the non-enzymatic biological properties, whose discovery 40 years ago started a new chapter in the study of ureases. Well recognized as virulence factors due to the production of ammonia and alkalinization in diseases by urease-positive microorganisms, ureases have pro-inflammatory, endocytosis-inducing and neurotoxic activities that do not require ureolysis. Particularly relevant in plants, ureases exert insecticidal and fungitoxic effects. Data on the jack bean urease and on jaburetox, a recombinant urease-derived peptide, have indicated that interactions with cell membrane lipids may be the basis of the non-enzymatic biological properties of ureases. Altogether, with this review we wanted to invite the readers to take a second look at ureases, very versatile proteins that happen also to catalyze the breakdown of urea into ammonia and carbamate.
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Affiliation(s)
- Karine Kappaun
- Brain Institute (InsCer), Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga 6690, Prédio 63, Porto Alegre, RS CEP 90610-000, Brazil
- Graduate Program in Medicine and Health Sciences, School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil
| | - Angela Regina Piovesan
- Brain Institute (InsCer), Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga 6690, Prédio 63, Porto Alegre, RS CEP 90610-000, Brazil
- Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Celia Regina Carlini
- Brain Institute (InsCer), Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga 6690, Prédio 63, Porto Alegre, RS CEP 90610-000, Brazil
- Graduate Program in Medicine and Health Sciences, School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil
| | - Rodrigo Ligabue-Braun
- Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
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Manuka honey ( Leptospermum scoparium ) inhibits jack bean urease activity due to methylglyoxal and dihydroxyacetone. Food Chem 2017; 230:540-546. [DOI: 10.1016/j.foodchem.2017.03.075] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Revised: 02/22/2017] [Accepted: 03/13/2017] [Indexed: 11/20/2022]
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Deutch CE. Limited effectiveness of over-the-counter plant preparations used for the treatment of urinary tract infections as inhibitors of the urease activity from Staphylococcus saprophyticus. J Appl Microbiol 2017; 122:1380-1388. [PMID: 28245081 DOI: 10.1111/jam.13430] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Revised: 02/08/2017] [Accepted: 02/16/2017] [Indexed: 12/24/2022]
Abstract
AIMS Urease is a key virulence factor for the Gram-positive urinary tract pathogen Staphylococcus saprophyticus and a potential target for antimicrobial therapy. The enzyme from S. saprophyticus is unusual in that it does not contain cysteine at the active site. The aims of this study were to test 14 over-the-counter plant preparations as inhibitors of this urease and to determine whether they can prevent the increase in pH that normally occurs in bacterial cultures containing urea. METHODS AND RESULTS Urease activity was measured colorimetrically by the formation of ammonium ions. The green tea and Uva-Ursi preparations reduced urease activity in a soluble extract of S. saprophyticus by more than 75%. Two herbal mixtures were weakly inhibitory and reduced activity by about 25%, but the other products had little or no effect. The green tea and Uva-Ursi extracts also inhibited urease activity in whole cells by more than 75%. One of the herbal products (WishGarden UTI) showed some inhibition of urease activity but the other (UTI Clear) did not. The green tea and Uva-Ursi preparations prevented the increase in pH that normally occurs when S. saprophyticus is grown in an artificial urine medium, but this was due primarily to bacterial death. The WishGarden UTI preparation could partially delay the pH increase while allowing some cells to remain viable. CONCLUSION These results indicate that only a few of the commercially available over-the-counter plant preparations commonly used for the treatment of urinary tract infections (UTIs) can inhibit the urease activity from S. saprophyticus. SIGNIFICANCE AND IMPACT OF THE STUDY While over-the-counter plant preparations may be considered an alternative to traditional antibiotics for the treatment of UTIs, they should be used with caution and a product should be matched to the properties of the virulence factors of the bacterial pathogen involved.
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Affiliation(s)
- C E Deutch
- Department of Biology, Creighton University, Omaha, NE, USA
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31
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Li Y, Hu X, Ding D, Zou Y, Xu Y, Wang X, Zhang Y, Chen L, Chen Z, Tan W. In situ targeted MRI detection of Helicobacter pylori with stable magnetic graphitic nanocapsules. Nat Commun 2017. [PMID: 28643777 PMCID: PMC5501158 DOI: 10.1038/ncomms15653] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Helicobacter pylori infection is implicated in the aetiology of many diseases. Despite numerous studies, a painless, fast and direct method for the in situ detection of H. pylori remains a challenge, mainly due to the strong acidic/enzymatic environment of the gastric mucosa. Herein, we report the use of stable magnetic graphitic nanocapsules (MGNs), for in situ targeted magnetic resonance imaging (MRI) detection of H. pylori. Several layers of graphene as the shell effectively protect the magnetic core from corrosion while retaining the superior contrast effect for MRI in the gastric environment. Boronic-polyethylene glycol molecules were synthesized and modified on the MGN surface for targeted MRI detection. In a mouse model of H. pylori-induced infection, H. pylori was specifically detected through both T2-weighted MR imaging and Raman gastric mucosa imaging using functionalized MGNs. These results indicated that enhancement of MRI using MGNs may be a promising diagnostic and bioimaging platform for very harsh conditions.
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Affiliation(s)
- Yunjie Li
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Xiaoxiao Hu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Ding Ding
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Yuxiu Zou
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Yiting Xu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Xuewei Wang
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Yin Zhang
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Long Chen
- Faculty of Science and Technology, University of Macau, Av. da Universidade, Taipa 999078, Macau
| | - Zhuo Chen
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Weihong Tan
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China.,Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at Bio/nano Interface, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200, USA
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Tan L, Li C, Chen H, Mo Z, Zhou J, Liu Y, Ma Z, Xu Y, Yang X, Xie J, Su Z. Epiberberine, a natural protoberberine alkaloid, inhibits urease of Helicobacter pylori and jack bean: Susceptibility and mechanism. Eur J Pharm Sci 2017; 110:77-86. [PMID: 28167234 DOI: 10.1016/j.ejps.2017.02.004] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2016] [Revised: 01/28/2017] [Accepted: 02/02/2017] [Indexed: 12/31/2022]
Abstract
In our previous study, Rhizoma Coptidis extract was found to exert more potent inhibitory effect than its major component berberine towards urease from Helicobacter pylori (HPU) and jack bean (JBU). In continuation of our work, the present study was designed to further comparatively investigate the urease inhibitory activities of five major protoberberine alkaloids in Rhizoma Coptidis, namely berberine, palmatine, coptisine, epiberberine, jateorhizine to identify the bioactive constituent, and illuminate the potential mechanism of action. Results indicated that the five protoberberine alkaloids acted as concentration-dependent inactivators of urease with IC50 values ranging between 3.0 and 5087μM for HPU and 2.3->10,000μM for JBU, respectively. Notably, epiberberine (EB) was found to be the most potent inhibitor against both ureases with IC50 values of 3.0±0.01μM for HPU and 2.3±0.01μM for JBU, which was more effective than the standard urease inhibitor, acetohydroxamic acid (83±0.01μM for HPU and 22±0.01μM for JBU, respectively). Further kinetic analysis revealed that the type of EB inhibition against HPU was slow-binding and uncompetitive, with Ki of 10.6±0.01μM, while slow-binding and competitive against JBU with Ki of 4.6±0.01μM. Addition of thiol reagents, such as l-cysteine, glutathione and dithiothreitol, significantly abolished the inhibition, while Ni2+ competitive inhibitors, boric acid and sodium fluoride, synergetically inhibited urease with EB, indicating the obligatory role of the active site sulfhydryl group for the inhibition. In addition, binding of EB with the urease proved to be reversible, as about 65% and 90% enzymatic activity of HPU and JBU, respectively, could be restored by dithiothreitol application. These findings highlighted the potential role of Rhizoma Coptidis protoberberine alkaloids, especially EB, as a lead urease inhibitor in the treatment of diseases associated with ureolytic bacteria. Thus, EB had good potential for further development into a promising therapeutic approach for the treatment of urease-related diseases.
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Affiliation(s)
- Lihua Tan
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, People's Republic of China
| | - Cailan Li
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, People's Republic of China
| | - Hanbin Chen
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, People's Republic of China
| | - Zhizhun Mo
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, People's Republic of China
| | - Jiangtao Zhou
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, People's Republic of China
| | - Yuhong Liu
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, People's Republic of China
| | - Zhilin Ma
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China
| | - Yuyao Xu
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China
| | - Xiaobo Yang
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, People's Republic of China
| | - Jianhui Xie
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, People's Republic of China.
| | - Ziren Su
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, People's Republic of China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523808, People's Republic of China.
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Zhou JT, Li CL, Tan LH, Xu YF, Liu YH, Mo ZZ, Dou YX, Su R, Su ZR, Huang P, Xie JH. Inhibition of Helicobacter pylori and Its Associated Urease by Palmatine: Investigation on the Potential Mechanism. PLoS One 2017; 12:e0168944. [PMID: 28045966 PMCID: PMC5207512 DOI: 10.1371/journal.pone.0168944] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Accepted: 12/08/2016] [Indexed: 01/17/2023] Open
Abstract
In this paper, we evaluated the anti-Helicobacter pylori activity and the possible inhibitory effect on its associated urease by Palmatine (Pal) from Coptis chinensis, and explored the potential underlying mechanism. Results indicated that Pal exerted inhibitory effect on four tested H. pylori strains (ATCC 43504, NCTC 26695, SS1 and ICDC 111001) by the agar dilution test with minimum inhibitory concentration (MIC) values ranging from 100 to 200 μg/mL under neutral environment (pH 7.4), and from 75 to 100 μg/mL under acidic conditions (pH 5.3), respectively. Pal was observed to significantly inhibit both H. pylori urease (HPU) and jack bean urease (JBU) in a dose-dependent manner, with IC50 values of 0.53 ± 0.01 mM and 0.03 ± 0.00 mM, respectively, as compared with acetohydroxamic acid, a well-known urease inhibitor (0.07 ± 0.01 mM for HPU and 0.02 ± 0.00 mM for JBU, respectively). Kinetic analyses showed that the type of urease inhibition by Pal was noncompetitive for both HPU and JBU. Higher effectiveness of thiol protectors against urease inhibition than the competitive Ni2+ binding inhibitors was observed, indicating the essential role of the active-site sulfhydryl group in the urease inhibition by Pal. DTT reactivation assay indicated that the inhibition on the two ureases was reversible, further supporting that sulfhydryl group should be obligatory for urease inhibition by Pal. Furthermore, molecular docking study indicated that Pal interacted with the important sulfhydryl groups and inhibited the active enzymatic conformation through N-H ∙ π interaction, but did not interact with the active site Ni2+. Taken together, Pal was an effective inhibitor of H. pylori and its urease targeting the sulfhydryl groups, representing a promising candidate as novel urease inhibitor. This investigation also gave additional scientific support to the use of C. chinensis to treat H. pylori-related gastrointestinal diseases in traditional Chinese medicine. Pal might be a potentially beneficial therapy for gastritis and peptic ulcers induced by H. pylori infection and other urease-related diseases.
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Affiliation(s)
- Jiang-Tao Zhou
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Cai-Lan Li
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Li-Hua Tan
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Yi-Fei Xu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Yu-Hong Liu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Zhi-Zhun Mo
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Yao-Xing Dou
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Rui Su
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Zi-Ren Su
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Ping Huang
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Jian-Hui Xie
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, PR China
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Anti-Helicobacter pylori activity of crude N-acetylneuraminic acid isolated from glycomacropeptide of whey. Lab Anim Res 2016; 32:99-104. [PMID: 27382378 PMCID: PMC4931043 DOI: 10.5625/lar.2016.32.2.99] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Revised: 06/01/2016] [Accepted: 06/06/2016] [Indexed: 12/15/2022] Open
Abstract
Helicobacter pylori colonizes the gastric mucosa of about half of the world's population, causing chronic gastritis and gastric cancer. An increasing emergence of antibiotic-resistant H. pylori arouses demand on alternative non-antibiotic-based therapies. In this study, we freshly prepared crude N-acetylneuraminic acid obtained from glycomacropeptide (G-NANA) of whey through a neuraminidase-mediated reaction and evaluated its antibacterial ability against H. pylori and H. felis. Overnight cultures of the H. pylori were diluted with fresh media and different concentrations (1-150 mg/mL) of crude G-NANA were added directly to the culture tube. Bacterial growth was evaluated by measuring the optical density of the culture medium and the number of viable bacteria was determined by a direct count of the colony forming units (CFU) on agar plates. For the in vivo study, mice were orally infected with 100 µL (5×10(8) cfu/mL) of H. felis four times at a day's interval, accompanied by a daily administration of crude G-NANA or vehicle. A day after the last infection, the mice were daily administered the crude G-NANA (0, 75, and 300 mg/mL) for 10 days and euthanized. Their stomachs were collected and bacterial colonization was determined by quantitative real-time PCR. Crude G-NANA inhibited H. pylori's growth and reduced the number of viable bacteria in a dose-dependent manner. Furthermore, crude G-NANA inhibited bacterial colonization in the mice. These results showed that crude G-NANA has antibacterial activity against Helicobacter and demonstrated its therapeutic potential for the prevention of chronic gastritis and gastric carcinogenesis induced by Helicobacter infection in humans.
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Hassan STS, Žemlička M. Plant-Derived Urease Inhibitors as Alternative Chemotherapeutic Agents. Arch Pharm (Weinheim) 2016; 349:507-22. [DOI: 10.1002/ardp.201500019] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Revised: 04/22/2016] [Accepted: 04/26/2016] [Indexed: 01/08/2023]
Affiliation(s)
- Sherif T. S. Hassan
- Faculty of Pharmacy; Department of Natural Drugs; University of Veterinary and Pharmaceutical Sciences Brno; Brno Czech Republic
| | - Milan Žemlička
- Department of Pharmacognosy and Botany; University of Veterinary Medicine and Pharmacy in Košice; Košice Slovak Republic
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Di Giulio M, Di Campli E, Di Bartolomeo S, Cataldi V, Marzio L, Grossi L, Ciccaglione AF, Nostro A, Cellini L. In vitro antimicrobial susceptibility of Helicobacter pylori to nine antibiotics currently used in Central Italy. Scand J Gastroenterol 2016; 51:263-9. [PMID: 26554617 DOI: 10.3109/00365521.2015.1092577] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Helicobacter pylori expresses an increased resistance in respect to antimicrobials currently used in therapy. The aim of this study was to evaluate the antimicrobial profiles of H. pylori isolates to nine conventional antibiotics used in a Central Region (Abruzzo) of Italy. MATERIALS AND METHODS Biopsies were taken from antrum and fundus of 112 adult and 3 children with Urea Breath Test positive with dyspeptic symptoms and analyzed for H. pylori culture and antibacterial activity. Antimicrobial susceptibility tests were performed for clarithromycin, metronidazole, levofloxacin, moxifloxacin, ciprofloxacin, tetracycline, amoxicillin, ampicillin, and rifabutin by a modified agar dilution susceptibility test. RESULTS Bacterial culture was successful in 100 out of 115 patients. Helicobacter pylori strains were isolated from 98 antrum and 83 fundus samples. The rate of recovery of H. pylori strains was 90.50% (181/200). The percentages of resistance were as follows: clarithromycin 72.44% antrum, 72.28% fundus; metronidazole 34.69% antrum, 42.16% fundus; levofloxacin 42.85% antrum, 53.01% fundus; moxifloxacin 37.35% antrum, 46.57% fundus; ciprofloxacin 39.47% antrum, 44.28% fundus; tetracycline 2.63% antrum, 2.85% fundus; amoxicillin 1.02% antrum, 1.20% fundus; ampicillin 0% antrum and fundus and rifabutin 0% antrum, 1.20% fundus. A total of 35 subjects harbored multi-resistant strains. CONCLUSIONS This study underlines the high rate of resistance to clarithromycin, metronidazole and quinolones, which may reflect an overuse of them. Culture and susceptibility test, should be performed to prevent the emergence of multi-resistance and to assess an efficacious regimen.
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Affiliation(s)
- Mara Di Giulio
- a Department of Pharmacy , University "G. d'Annunzio" Chieti-Pescara , Chieti , Italy
| | - Emanuela Di Campli
- a Department of Pharmacy , University "G. d'Annunzio" Chieti-Pescara , Chieti , Italy
| | - Soraya Di Bartolomeo
- a Department of Pharmacy , University "G. d'Annunzio" Chieti-Pescara , Chieti , Italy
| | - Valentina Cataldi
- a Department of Pharmacy , University "G. d'Annunzio" Chieti-Pescara , Chieti , Italy
| | - Leonardo Marzio
- b Digestive Physiopathology Unit, University "G. d'Annunzio" Chieti-Pescara, Pescara Civic Hospital , Italy
| | - Laurino Grossi
- b Digestive Physiopathology Unit, University "G. d'Annunzio" Chieti-Pescara, Pescara Civic Hospital , Italy
| | | | - Antonia Nostro
- c Department of Pharmaceutical Sciences and Health Products , University of Messina , Messina , Italy
| | - Luigina Cellini
- a Department of Pharmacy , University "G. d'Annunzio" Chieti-Pescara , Chieti , Italy
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Ansari S, Gautam R, Nepal HP, Subedi SN, Shrestha S, Mandal F, Rimal B, Chhetri MR. Helicobacter pylori colonization in Nepal; assessment of prevalence and potential risk factors in a hospital-based patient cohort. BMC Res Notes 2016; 9:59. [PMID: 26833400 PMCID: PMC4736165 DOI: 10.1186/s13104-016-1867-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Accepted: 01/15/2016] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Helicobacter pylori, a gram-negative bacterium, can cause gastritis, peptic and duodenal ulcers. It is considered an important public health problem for both developed and developing world. This bacterium is classified as the class 1 carcinogen because it can cause cancer. METHODS A hospital based study was conducted at Chitwan Medical College Teaching Hospital (CMCTH) from May to October 2014. Stool samples were collected from the suspected patients and were subjected to detection of the H. pylori stool antigen (HpSAg) following the procedures recommended by the manufacturer. A standard questionnaire on the potential risk factors was also designed and completed. RESULT HpSAg was detected in 16 % of suspected patients. The children up to 10 years of age were found to be highly infected (36 %). The patients living in urban area were found more susceptible to develop H. pylori infection (P < 0.05). Tea drinking and repeated eating habit (more than twice a day) were listed as the important factors that can limit the H. pylori infections significantly (P < 0.05). CONCLUSION In this hospital based study, a significant rate of prevalence was evaluated. However, we recommend a community based extensive study to reveal the real scenario of H. pylori infection in Nepalese populations.
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Affiliation(s)
- Shamshul Ansari
- Department of Microbiology, Chitwan Medical College, Bharatpur, Chitwan, Nepal.
| | - Rajendra Gautam
- Department of Microbiology, Chitwan Medical College, Bharatpur, Chitwan, Nepal.
| | - Hari Prasad Nepal
- Department of Microbiology, Chitwan Medical College, Bharatpur, Chitwan, Nepal.
| | - Shankar Nand Subedi
- School of Public Health and Community Medicine, Chitwan Medical College, Bharatpur, Chitwan, Nepal.
| | - Sony Shrestha
- Department of Microbiology, Chitwan Medical College, Bharatpur, Chitwan, Nepal.
| | - Fuleshwar Mandal
- Department of Biochemistry, Chitwan Medical College, Bharatpur, Chitwan, Nepal.
| | - Brihaspati Rimal
- Department of Biochemistry, Chitwan Medical College, Bharatpur, Chitwan, Nepal.
| | - Muni Raj Chhetri
- School of Public Health and Community Medicine, Chitwan Medical College, Bharatpur, Chitwan, Nepal.
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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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Safavi M, Shams-Ardakani M, Foroumadi A. Medicinal plants in the treatment of Helicobacter pylori infections. PHARMACEUTICAL BIOLOGY 2015; 53:939-960. [PMID: 25430849 DOI: 10.3109/13880209.2014.952837] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
CONTEXT Helicobacter pylori is a small, spiral, Gram-negative bacillus that plays a role in the pathogenesis of a number of diseases ranging from asymptomatic gastritis to gastric cancer. Schedule compliance, antibiotic drug resistance, and side-effects of triple or quadruple therapy have led to research for novel candidates from plants. OBJECTIVE The purpose of this paper is to review the most potent medicinal plants of recently published literature with anti-H. pylori activity. For centuries, herbals have been used by traditional healers around the world to treat various gastrointestinal tract disorders such as dyspepsia, gastritis, and peptic ulcer disease. The mechanism of action by which these botanicals exert their therapeutic properties has not been completely and clearly elucidated. Anti-H. pylori properties may be one of the possible mechanisms by which gastroprotective herbs treat gastrointestinal tract disorders. MATERIALS AND METHODS Electronic databases such as PubMed, Google scholar, EBSCO, and local databases were explored for medicinal plants with anti-H. pylori properties between 1984 and 2013 using key words "medicinal plants" and "Helicobacter pylori" or "anti-Helicobacter pylori". RESULTS A total of 43 medicinal plant species belonging to 27 families including Amaryllidaceae, Anacardiaceae, Apiaceae, Apocynaceae, Asclepiadoideae, Asteraceae, Bignoniaceae, Clusiaceae, Chancapiedra, Combretaceae, Cyperaceae, Euphorbiaceae, Fabaceae, Geraniaceae, Lamiaceae, Lauraceae, Lythraceae, Menispermaceae, Myristicaceae, Myrtaceae, Oleaceae, Papaveraceae, Plumbaginaceae, Poaceae, Ranunculaceae, Rosaceae, and Theaceae were studied as herbs with potent anti-H. pylori effects. CONCLUSION Traditional folk medicinal use of some of these plants to treat gastric infections is substantiated by the antibacterial activity of their extracts against H. pylori.
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Affiliation(s)
- Maliheh Safavi
- Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST) , Tehran , Iran
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Fahey JW, Stephenson KK, Wallace AJ. Dietary amelioration of Helicobacter infection. Nutr Res 2015; 35:461-73. [PMID: 25799054 PMCID: PMC4465045 DOI: 10.1016/j.nutres.2015.03.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Revised: 03/01/2015] [Accepted: 03/02/2015] [Indexed: 12/18/2022]
Abstract
We review herein the basis for using dietary components to treat and/or prevent Helicobacter pylori infection, with emphasis on (a) work reported in the last decade, (b) dietary components for which there is mechanism-based plausibility, and (c) components for which clinical results on H pylori amelioration are available. There is evidence that a diet-based treatment may reduce the levels and/or the virulence of H pylori colonization without completely eradicating the organism in treated individuals. This concept was endorsed a decade ago by the participants in a small international consensus conference held in Honolulu, Hawaii, USA, and interest in such a diet-based approach has increased dramatically since then. This approach is attractive in terms of cost, treatment, tolerability, and cultural acceptability. This review, therefore, highlights specific foods, food components, and food products, grouped as follows: bee products (eg, honey and propolis); probiotics; dairy products; vegetables; fruits; oils; essential oils; and herbs, spices, and other plants. A discussion of the small number of clinical studies that are available is supplemented by supportive in vitro and animal studies. This very large body of in vitro and preclinical evidence must now be followed up with rationally designed, unambiguous human trials.
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Affiliation(s)
- Jed W Fahey
- Lewis B. and Dorothy Cullman Chemoprotection Center, Department of Pharmacology & Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Center for Human Nutrition, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
| | - Katherine K Stephenson
- Lewis B. and Dorothy Cullman Chemoprotection Center, Department of Pharmacology & Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Alison J Wallace
- New Zealand Institute for Plant and Food Research Limited, Lincoln, New Zealand
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Yu XD, Zheng RB, Xie JH, Su JY, Huang XQ, Wang YH, Zheng YF, Mo ZZ, Wu XL, Wu DW, Liang YE, Zeng HF, Su ZR, Huang P. Biological evaluation and molecular docking of baicalin and scutellarin as Helicobacter pylori urease inhibitors. JOURNAL OF ETHNOPHARMACOLOGY 2015; 162:69-78. [PMID: 25557028 DOI: 10.1016/j.jep.2014.12.041] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 09/07/2014] [Accepted: 12/22/2014] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Baicalin and scutellarin are the principal bioactive components of Scutellaria baicalensis Georgi which has extensively been incorporated into heat-clearing and detoxification formulas for the treatment of Helicobacter pylori-related gastrointestinal disorders in traditional Chinese medicine. However, the mechanism of action remained to be defined. AIM OF THE STUDY To explore the inhibitory effect, kinetics and mechanism of Helicobacter pylori urease (the vital pathogenetic factor for Helicobacter pylori infection) inhibition by baicalin and scutellarin, for their therapeutic potential. MATERIALS AND METHODS The ammonia formations, indicator of urease activity, were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. The inhibitory effect of baicalin and scutellarin was characterized with IC50 values, compared to acetohydroxamic acid (AHA), a well known Helicobacter pylori urease inhibitor. Lineweaver-Burk and Dixon plots for the Helicobacter pylori urease inhibition of baicalin and scutellarin was constructed from the kinetic data. SH-blocking reagents and competitive active site Ni(2+) binding inhibitors were employed for mechanism study. Molecular docking technique was used to provide some information on binding conformations as well as confirm the inhibition mode. Moreover, cytotoxicity experiment using Gastric Epithelial Cells (GES-1) was evaluated. RESULTS Baicalin and scutellarin effectively suppressed Helicobacter pylori urease in dose-dependent and time-independent manner with IC50 of 0.82±0.07 mM and 0.47±0.04 mM, respectively, compared to AHA (IC50=0.14±0.05 mM). Structure-activity relationship disclosed 4'-hydroxyl gave flavones an advantage to binding with Helicobacter pylori urease. Kinetic analysis revealed that the types of inhibition were non-competitive and reversible with inhibition constant Ki of 0.14±0.01 mM and 0.18±0.02 mM for baicalin and scutellarin, respectively. The mechanism of urease inhibition was considered to be blockage of the SH groups of Helicobacter pylori urease, since thiol reagents (L,D-dithiothreitol, L-cysteine and glutathione) abolished the inhibitory action and competitive active site Ni(2+) binding inhibitors (boric acid and sodium fluoride) carried invalid effect. Molecular docking study further supported the structure-activity analysis and indicated that baicalin and scutellarin interacted with the key residues Cys321 located on the mobile flap through S-H·π interaction, but did not interact with active site Ni(2+). Moreover, Baicalin (at 0.59-1.05 mM concentrations) and scutellarin (at 0.23-0.71 mM concentrations) did not exhibit significant cytotoxicity to GES-1. CONCLUSIONS Baicalin and scutellarin were non-competitive inhibitors targeting sulfhydryl groups especially Cys321 around the active site of Helicobacter pylori urease, representing potential to be good candidate for future research as urease inhibitor for treatment of Helicobacter pylori infection. Furthermore, our work gave additional scientific support to the use of Scutellaria baicalensis in traditional Chinese medicine (TCM) to treat gastrointestinal disorders.
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Affiliation(s)
- Xiao-Dan Yu
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Rong-Bo Zheng
- Guangzhou Wanglaoji Pharmaceutical Company Limited, Guangzhou, Guangdong 510450, P.R. China
| | - Jian-Hui Xie
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, P.R. China
| | - Ji-Yan Su
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Xiao-Qi Huang
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, P.R. China
| | - Yong-Hong Wang
- Guangdong Institute of Microbiology, Guangzhou 510006, P.R. China
| | - Yi-Feng Zheng
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Zhi-Zhun Mo
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Xiao-Li Wu
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Dian-Wei Wu
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Ye-er Liang
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Hui-Fang Zeng
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, P.R. China.
| | - Zi-Ren Su
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou, University of Chinese Medicine, Dongguan 523000, P.R. China
| | - Ping Huang
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China.
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Dietary functional benefits of Bartlett and Starkrimson pears for potential management of hyperglycemia, hypertension and ulcer bacteria Helicobacter pylori while supporting beneficial probiotic bacterial response. Food Res Int 2015. [DOI: 10.1016/j.foodres.2014.12.014] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Macomber L, Minkara MS, Hausinger RP, Merz KM. Reduction of urease activity by interaction with the flap covering the active site. J Chem Inf Model 2015; 55:354-61. [PMID: 25594724 DOI: 10.1021/ci500562t] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
With the increasing appreciation for the human microbiome coupled with the global rise of antibiotic resistant organisms, it is imperative that new methods be developed to specifically target pathogens. To that end, a novel computational approach was devised to identify compounds that reduce the activity of urease, a medically important enzyme of Helicobacter pylori, Proteus mirabilis, and many other microorganisms. Urease contains a flexible loop that covers its active site; Glide was used to identify small molecules predicted to lock this loop in an open conformation. These compounds were screened against the model urease from Klebsiella aerogenes, and the natural products epigallocatechin and quercetin were shown to inhibit at low and high micromolar concentrations, respectively. These molecules exhibit a strong time-dependent inactivation of urease that was not due to their oxygen sensitivity. Rather, these compounds appear to inactivate urease by reacting with a specific Cys residue located on the flexible loop. Substitution of this cysteine by alanine in the C319A variant increased the urease resistance to both epigallocatechin and quercetin, as predicted by the computational studies. Protein dynamics are integral to the function of many enzymes; thus, identification of compounds that lock an enzyme into a single conformation presents a useful approach to define potential inhibitors.
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Affiliation(s)
- Lee Macomber
- Department of Microbiology & Molecular Genetics, Biomedical Physical Sciences Building and ∥Department of Biochemistry & Molecular Biology, Biomedical Physical Sciences Building, Michigan State University , Room 2215, 567 Wilson Road, East Lansing, Michigan 48824, United States
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Modolo LV, de Souza AX, Horta LP, Araujo DP, de Fátima Â. An overview on the potential of natural products as ureases inhibitors: A review. J Adv Res 2014; 6:35-44. [PMID: 25685542 PMCID: PMC4293669 DOI: 10.1016/j.jare.2014.09.001] [Citation(s) in RCA: 116] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2014] [Revised: 09/21/2014] [Accepted: 09/22/2014] [Indexed: 01/18/2023] Open
Abstract
Ureases, enzymes that catalyze urea hydrolysis, have received considerable attention for their impact on living organisms’ health and life quality. On the one hand, the persistence of urease activity in human and animal cells can be the cause of some diseases and pathogen infections. On the other hand, food production can be negatively affected by ureases of soil microbiota that, in turn, lead to losses of nitrogenous nutrients in fields supplemented with urea as fertilizer. In this context, nature has proven to be a rich resource of natural products bearing a variety of scaffolds that decrease the ureolytic activity of ureases from different organisms. Therefore, this work compiles the state-of-the-art researches focused on the potential of plant natural products (present in extracts or as pure compounds) as urease inhibitors of clinical and/or agricultural interests. Emphasis is given to ureases of Helicobacter pylori, Canavalia ensiformis and soil microbiota although the active site of this class of hydrolases is conserved among living organisms.
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Affiliation(s)
- Luzia V. Modolo
- Departamento de Botânica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil
- Corresponding authors. Tel./fax: +55 31 3409 3008 (L.V. Modolo). Tel.: +55 31 3409 6373; fax: +55 31 3409 5700 (A. de Fátima).
| | - Aline X. de Souza
- Departamento de Botânica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil
| | - Lívia P. Horta
- Departamento de Botânica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil
| | - Débora P. Araujo
- Departamento de Botânica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil
- Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil
| | - Ângelo de Fátima
- Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil
- Corresponding authors. Tel./fax: +55 31 3409 3008 (L.V. Modolo). Tel.: +55 31 3409 6373; fax: +55 31 3409 5700 (A. de Fátima).
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Yu XD, Xie JH, Wang YH, Li YC, Mo ZZ, Zheng YF, Su JY, Liang YE, Liang JZ, Su ZR, Huang P. Selective Antibacterial Activity of Patchouli Alcohol Against Helicobacter pylori
Based on Inhibition of Urease. Phytother Res 2014; 29:67-72. [DOI: 10.1002/ptr.5227] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2014] [Revised: 08/22/2014] [Accepted: 08/26/2014] [Indexed: 11/10/2022]
Affiliation(s)
- Xiao-Dan Yu
- College of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou 510006 PR China
| | - Jian-Hui Xie
- College of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou 510006 PR China
- The Second Affiliated Hospital of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou 510115 PR China
| | - Yong-Hong Wang
- Guangdong Institute of Microbiology; Guangzhou 510006 PR China
| | - Yu-Cui Li
- College of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou 510006 PR China
| | - Zhi-Zhun Mo
- College of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou 510006 PR China
| | - Yi-Feng Zheng
- College of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou 510006 PR China
| | - Ji-Yan Su
- College of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou 510006 PR China
| | - Ye-er Liang
- College of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou 510006 PR China
| | - Jin-Zhi Liang
- College of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou 510006 PR China
| | - Zi-Ren Su
- College of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou 510006 PR China
- Dongguan Mathematical Engineering Academy of Chinese Medicine; Guangzhou University of Chinese Medicine; Dongguan 523000 PR China
| | - Ping Huang
- College of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou 510006 PR China
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Wang YC. Medicinal plant activity on Helicobacter pylori related diseases. World J Gastroenterol 2014; 20:10368-10382. [PMID: 25132753 PMCID: PMC4130844 DOI: 10.3748/wjg.v20.i30.10368] [Citation(s) in RCA: 103] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Revised: 01/17/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori eradication and H. pylori induced related gastric disease prevention.
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Panno ML, Giordano F. Effects of psoralens as anti-tumoral agents in breast cancer cells. World J Clin Oncol 2014; 5:348-358. [PMID: 25114850 PMCID: PMC4127606 DOI: 10.5306/wjco.v5.i3.348] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Revised: 05/14/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023] Open
Abstract
This review examines the biological properties of coumarins, widely distributed at the highest levels in the fruit, followed by the roots, stems and leaves, by considering their beneficial effects in the prevention of some diseases and as anti-cancer agents. These compounds are well known photosensitizing drugs which have been used as pharmaceuticals for a broad number of therapeutic applications requiring cell division inhibitors. Despite this, even in the absence of ultraviolet rays they are active. The current paper mainly focuses on the effects of psoralens on human breast cancer as they are able to influence many aspects of cell behavior, such as cell growth, survival and apoptosis. In addition, analytical and pharmacological data have demonstrated that psoralens antagonize some metabolizing enzymes, affect estrogen receptor stability and counteract cell invasiveness as well as cancer drug resistance. The scientific findings summarized highlight the pleiotropic functions of phytochemical drugs, given that recently their target signals and how these are modified in the cells have been identified. The encouraging results in this field suggest that multiple modulating strategies based on coumarin drugs in combination with canonical chemotherapeutic agents or radiotherapy could be a useful approach to address the treatment of many types of cancer.
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Takeuchi H, Trang VT, Morimoto N, Nishida Y, Matsumura Y, Sugiura T. Natural products and food components with anti- Helicobacter pylori activities. World J Gastroenterol 2014; 20:8971-8978. [PMID: 25083070 PMCID: PMC4112882 DOI: 10.3748/wjg.v20.i27.8971] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 01/20/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
The bacterial pathogen Helicobacter pylori (H. pylori) colonizes in over half of the world’s population. H. pylori that establishes life-long infection in the stomach is definitely associated with gastro-duodenal diseases and a wide variety of non-gastrointestinal tract conditions such as immune thrombocytopenia. Triple therapy which consists of a proton pump inhibitor and combinations of two antibiotics (amoxicillin, clarithromycin or amoxicillin, metronidazol) is commonly used for H. pylori eradication. Recently, the occurrence of drug-resistant H. pylori and the adverse effect of antibiotics have severely weakened eradication therapy. Generally antibiotics induce the disturbance of human gastrointestinal microflora. Furthermore, there are inappropriate cases of triple therapy such as allergy to antibiotics, severe complications (liver and/or kidney dysfunction), the aged and people who reject the triple therapy. These prompt us to seek alterative agents instead of antibiotics and to develop more effective and safe therapy with these agents. The combination of these agents actually may result in lower a dose of antibiotics. There are many reports world-wide that non-antibiotic substances from natural products potentially have an anti-H. pylori agent. We briefly review the constituents derived from nature that fight against H. pylori in the literature with our studies.
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Vale FF, Oleastro M. Overview of the phytomedicine approaches against Helicobacter pylori. World J Gastroenterol 2014; 20:5594-5609. [PMID: 24914319 PMCID: PMC4024768 DOI: 10.3748/wjg.v20.i19.5594] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 12/18/2013] [Accepted: 03/06/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) successfully colonizes the human stomach of the majority of the human population. This infection always causes chronic gastritis, but may evolve to serious outcomes, such as peptic ulcer, gastric carcinoma or mucosa-associated lymphoid tissue lymphoma. H. pylori first line therapy recommended by the Maastricht-4 Consensus Report comprises the use of two antibiotics and a proton-pomp inhibitor, but in some regions failure associated with this treatment is already undesirable high. Indeed, treatment failure is one of the major problems associated with H. pylori infection and is mainly associated with bacterial antibiotic resistance. In order to counteract this situation, some effort has been allocated during the last years in the investigation of therapeutic alternatives beyond antibiotics. These include vaccines, probiotics, photodynamic inactivation and phage therapy, which are briefly revisited in this review. A particular focus on phytomedicine, also described as herbal therapy and botanical therapy, which consists in the use of plant extracts for medicinal purposes, is specifically addressed, namely considering its history, category of performed studies, tested compounds, active principle and mode of action. The herbs already experienced are highly diverse and usually selected from products with a long history of employment against diseases associated with H. pylori infection from each country own folk medicine. The studies demonstrated that many phytomedicine products have an anti-H. pylori activity and gastroprotective action. Although the mechanism of action is far from being completely understood, current knowledge correlates the beneficial action of herbs with inhibition of essential H. pylori enzymes, modulation of the host immune system and with attenuation of inflammation.
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Lee HK, Song HE, Lee HB, Kim CS, Koketsu M, Thi My Ngan L, Ahn YJ. Growth inhibitory, bactericidal, and morphostructural effects of dehydrocostus lactone from Magnolia sieboldii Leaves on antibiotic-susceptible and -resistant strains of Helicobacter pylori. PLoS One 2014; 9:e95530. [PMID: 24747984 PMCID: PMC3991664 DOI: 10.1371/journal.pone.0095530] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2014] [Accepted: 03/21/2014] [Indexed: 01/25/2023] Open
Abstract
Helicobacter pylori is associated with various diseases of the upper gastrointestinal tract, such as gastric inflammation and duodenal and gastric ulcers. The aim of the study was to assess anti-H. pylori effects of the sesquiterpene lactone dehydrocostus lactone (DCL) from Magnolia sieboldii leaves, compared to commercial pure DCL, two previously known sesquiterpene lactones (costunolide and parthenolide), (-)-epigallocatechin gallate, and four antibiotics. The antibacterial activity of natural DCL toward antibiotic-susceptible H. pylori ATCC 700392 and H. pylori ATCC 700824 strains (MIC, 4.9 and 4.4 mg/L) was similar to that of commercial DCL and was more effective than costunolide, parthenolide, and EGCG. The activity of DCL was slightly lower than that of metronidazole (MIC, 1.10 and 1.07 mg/L). The antibacterial activity of DCL was virtually identical toward susceptible and resistant strains, even though resistance to amoxicillin (MIC, 11.1 mg/L for PED 503G strain), clarithromycin (49.8 mg/L for PED 3582GA strain), metronidazole (21.6 mg/L for H. pylori ATCC 43504 strain; 71.1 mg/L for 221 strain), or tetracycline (14.2 mg/L for B strain) was observed. This finding indicates that DCL and the antibiotics do not share a common mode of action. The bactericidal activity of DCL toward H. pylori ATCC 43504 was not affected by pH values examined (4.0-7.0). DCL caused considerable conversion to coccoid form (94 versus 49% at 8 and 4 mg/L of DCL for 48 h). The Western blot analysis revealed that urease subunits (UreA and UreB) of H. pylori ATCC 43504 were not affected by 10 mM of DCL, whereas UreA monomer band completely disappeared at 0.1 mM of (-)-epigallocatechin gallate. Global efforts to reduce the level of antibiotics justify further studies on M. sieboldii leaf-derived materials containing DCL as potential antibacterial products or a lead molecule for the prevention or eradication of drug-resistant H. pylori.
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Affiliation(s)
- Hyun-Kyung Lee
- Interdisciplinary Program in Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea
| | - Ha Eun Song
- Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea
| | - Haeng-Byung Lee
- Interdisciplinary Program in Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea
| | - Cheol-Soo Kim
- Halla Botanical Garden, Jeju City, Jeju, South Korea
| | - Mamoru Koketsu
- Department of Chemistry and Biomolecular Science, Gifu University, Gifu, Japan
| | - Luong Thi My Ngan
- Department of Plant Biotechnology and Biotransformation, Faculty of Biology, Ho Chi Minh City University of Science, Vietnam National University, Ho Chi Minh City, Vietnam
- * E-mail: (Y-JA); (LTMN)
| | - Young-Joon Ahn
- Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea
- * E-mail: (Y-JA); (LTMN)
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