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Meng T, Wen Z, Cheng X, Li C, Zhang P, Xiao D, Xu Y. Unlocking Gut Health: The Potent Role of Stilbenoids in Intestinal Homeostasis. Animals (Basel) 2025; 15:417. [PMID: 39943187 PMCID: PMC11816141 DOI: 10.3390/ani15030417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 01/28/2025] [Accepted: 01/29/2025] [Indexed: 02/16/2025] Open
Abstract
Stilbenoids are a class of naturally occurring phenolic compounds found in various plant species, characterized by a stilbene backbone with diverse substituents that confer a range of biological activities. These compounds exhibit antioxidant, anti-inflammatory, and antimicrobial properties, making them promising candidates for improving intestinal health. The intestinal tract plays a critical role in nutrient digestion, absorption, and immune defense, and maintaining its integrity is vital for animal growth. Stilbenoids contribute to gut health by enhancing intestinal morphology, supporting mucosal immune responses, regulating gut microbiota composition, modulating metabolic pathways, and maintaining mitochondrial health. This review provides a comprehensive analysis of key stilbenoids, including resveratrol, pterostilbene, piceatannol, and oxyresveratrol, focusing on their biological effects and regulatory mechanisms. By highlighting their roles in mitigating intestinal inflammation and promoting gut function, this review provides a basis for the practical application of stilbenoids in animal health and husbandry.
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Affiliation(s)
- Tiantian Meng
- College of Life Science, Xinyang Normal University, Xinyang 464000, China; (T.M.); (Z.W.); (X.C.); (C.L.); (P.Z.)
| | - Ziwei Wen
- College of Life Science, Xinyang Normal University, Xinyang 464000, China; (T.M.); (Z.W.); (X.C.); (C.L.); (P.Z.)
| | - Xiaofang Cheng
- College of Life Science, Xinyang Normal University, Xinyang 464000, China; (T.M.); (Z.W.); (X.C.); (C.L.); (P.Z.)
| | - Cencen Li
- College of Life Science, Xinyang Normal University, Xinyang 464000, China; (T.M.); (Z.W.); (X.C.); (C.L.); (P.Z.)
| | - Pengpeng Zhang
- College of Life Science, Xinyang Normal University, Xinyang 464000, China; (T.M.); (Z.W.); (X.C.); (C.L.); (P.Z.)
| | - Dingfu Xiao
- Yuelushan Laboratory, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Yongjie Xu
- College of Life Science, Xinyang Normal University, Xinyang 464000, China; (T.M.); (Z.W.); (X.C.); (C.L.); (P.Z.)
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Ma X, Huang T, Li X, Zhou X, Pan H, Du A, Zeng Y, Yuan K, Wang Z. Exploration of the link between COVID-19 and gastric cancer from the perspective of bioinformatics and systems biology. Front Med (Lausanne) 2024; 11:1428973. [PMID: 39371335 PMCID: PMC11449776 DOI: 10.3389/fmed.2024.1428973] [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: 05/07/2024] [Accepted: 09/04/2024] [Indexed: 10/08/2024] Open
Abstract
Background Coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused a global pandemic. Gastric cancer (GC) poses a great threat to people's health, which is a high-risk factor for COVID-19. Previous studies have found some associations between GC and COVID-19, whereas the underlying molecular mechanisms are not well understood. Methods We employed bioinformatics and systems biology to explore these links between GC and COVID-19. Gene expression profiles of COVID-19 (GSE196822) and GC (GSE179252) were obtained from the Gene Expression Omnibus (GEO) database. After identifying the shared differentially expressed genes (DEGs) for GC and COVID-19, functional annotation, protein-protein interaction (PPI) network, hub genes, transcriptional regulatory networks and candidate drugs were analyzed. Results We identified 209 shared DEGs between COVID-19 and GC. Functional analyses highlighted immune-related pathways as key players in both diseases. Ten hub genes (CDK1, KIF20A, TPX2, UBE2C, HJURP, CENPA, PLK1, MKI67, IFI6, IFIT2) were identified. The transcription factor/gene and miRNA/gene interaction networks identified 38 transcription factors (TFs) and 234 miRNAs. More importantly, we identified ten potential therapeutic agents, including ciclopirox, resveratrol, etoposide, methotrexate, trifluridine, enterolactone, troglitazone, calcitriol, dasatinib and deferoxamine, some of which have been reported to improve and treat GC and COVID-19. Conclusion This research offer valuable insights into the molecular interplay between COVID-19 and GC, potentially guiding future therapeutic strategies.
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Affiliation(s)
| | | | | | | | | | | | | | - Kefei Yuan
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Zhen Wang
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
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Spósito L, Fonseca D, Gonçalves Carvalho S, Sábio RM, Marena GD, Bauab TM, Bagliotti Meneguin A, Parreira P, L Martins MC, Chorilli M. Engineering resveratrol-loaded chitosan nanoparticles for potential use against Helicobacter pylori infection. Eur J Pharm Biopharm 2024; 199:114280. [PMID: 38588828 DOI: 10.1016/j.ejpb.2024.114280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 04/04/2024] [Accepted: 04/05/2024] [Indexed: 04/10/2024]
Abstract
Helicobacter pylori (H. pylori) is a microorganism directly linked to severe clinical conditions affecting the stomach. The virulence factors and its ability to form biofilms increase resistance to conventional antibiotics, growing the need for new substances and strategies for the treatment of H. pylori infection. The trans-resveratrol (RESV), a bioactive polyphenol from natural sources, has a potential activity against this gastric pathogen. Here, Chitosan nanoparticles (NP) containing RESV (RESV-NP) were developed for H. pylori management. The RESV-NP were prepared using the ionic gelation method and characterized by Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA) and, Cryogenic Transmission Electron Microscopy (Cryo - TEM). The encapsulation efficiency (EE) and in vitro release rate of RESV were quantified using high-performance liquid chromatography (HPLC). RESV-NP performance against H. pylori was evaluated by the quantification of the minimum inhibitory/bactericidal concentrations (MIC/MBC), time to kill, alterations in H. pylori morphology in its planktonic form, effects against H. pylori biofilm and in an in vitro infection model. RESV-NP cytotoxicity was evaluated against AGS and MKN-74 cell lines and by hemolysis assay. Acute toxicity was tested using Galleria mellonella model assays. RESV-NP showed a spherical shape, size of 145.3 ± 24.7 nm, polydispersity index (PDI) of 0.28 ± 0.008, and zeta potential (ZP) of + 16.9 ± 1.81 mV in DLS, while particle concentration was 3.12 x 1011 NP/mL (NTA). RESV-NP EE was 72 %, with full release within the first 5 min. In microbiological assays, RESV-NP presented a MIC/MBC of 3.9 µg/mL, a time to kill of 24 h for complete eradication of H. pylori. At a concentration of 2xMIC (7.8 µg/mL), RESV-NP completely eradicated the H. pylori biofilm, and in an in vitro infection model, RESV-NP (4xMIC - 15.6 µg/mL) showed a significant decrease in bacterial load (1 Log10CFU/mL) when compared to the H. pylori J99 control. In addition, they did not demonstrate a toxic character at MIC concentration for both cell lines. The use of the RESV-NP with mucoadhesion profile is an interesting strategy for oral administration of substances targeting gastric disorders, linked to H. pylori infections.
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Affiliation(s)
- Larissa Spósito
- São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Drugs and Medicines, Araraquara, SP, Brazil; São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Biological Sciences, Araraquara, SP, Brazil; i3S-Instituto de Investigação e Inovação em Saúde, Rua Alfredo Allen, 208, Porto 4200-135, Portugal; INEB-Instituto de Engenharia Biomédica, Rua Alfredo Allen, 208, Porto 4200-135, Portugal
| | - Diana Fonseca
- i3S-Instituto de Investigação e Inovação em Saúde, Rua Alfredo Allen, 208, Porto 4200-135, Portugal; INEB-Instituto de Engenharia Biomédica, Rua Alfredo Allen, 208, Porto 4200-135, Portugal
| | - Suzana Gonçalves Carvalho
- São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Drugs and Medicines, Araraquara, SP, Brazil
| | - Rafael Miguel Sábio
- São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Drugs and Medicines, Araraquara, SP, Brazil
| | - Gabriel Davi Marena
- São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Drugs and Medicines, Araraquara, SP, Brazil; São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Biological Sciences, Araraquara, SP, Brazil
| | - Taís Maria Bauab
- São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Biological Sciences, Araraquara, SP, Brazil
| | - Andréia Bagliotti Meneguin
- São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Drugs and Medicines, Araraquara, SP, Brazil
| | - Paula Parreira
- i3S-Instituto de Investigação e Inovação em Saúde, Rua Alfredo Allen, 208, Porto 4200-135, Portugal; INEB-Instituto de Engenharia Biomédica, Rua Alfredo Allen, 208, Porto 4200-135, Portugal
| | - M Cristina L Martins
- i3S-Instituto de Investigação e Inovação em Saúde, Rua Alfredo Allen, 208, Porto 4200-135, Portugal; INEB-Instituto de Engenharia Biomédica, Rua Alfredo Allen, 208, Porto 4200-135, Portugal.
| | - Marlus Chorilli
- São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Drugs and Medicines, Araraquara, SP, Brazil.
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Antimicrobial activity of oregano essential oil and resveratrol emulsions co-encapsulated by sodium caseinate with polysaccharides. Food Control 2022. [DOI: 10.1016/j.foodcont.2022.108925] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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A new approach against Helicobacter pylori using plants and its constituents: A review study. Microb Pathog 2022; 168:105594. [PMID: 35605740 DOI: 10.1016/j.micpath.2022.105594] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 05/11/2022] [Accepted: 05/15/2022] [Indexed: 02/07/2023]
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Di Fermo P, Di Lodovico S, Amoroso R, De Filippis B, D’Ercole S, Di Campli E, Cellini L, Di Giulio M. Searching for New Tools to Counteract the Helicobacter pylori Resistance: The Positive Action of Resveratrol Derivatives. Antibiotics (Basel) 2020; 9:E891. [PMID: 33322025 PMCID: PMC7763357 DOI: 10.3390/antibiotics9120891] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/04/2020] [Accepted: 12/08/2020] [Indexed: 01/02/2023] Open
Abstract
The drug-resistance phenomenon in Helicobacter pylori underlines the need of novel strategies to improve the eradication rate including alternative treatments combining antibiotic and non-antibiotic compounds with synergistic action. In this study, the antibacterial (MIC/MBC) and anti-virulence effects (biofilm reduction and swarming motility inhibition) of resveratrol-RSV and new synthetized RSV-phenol derivatives, with a higher bioavailability, alone and combined with levofloxacin-LVX were evaluated against resistant H. pylori clinical strains. The experiments were confirmed in vivo using the Galleria mellonella model. Among the studied RSV derivatives, RSV-3 and RSV-4 possessed higher antibacterial activity with respect to RSV (MICs from 6.25 to 200 µg/mL and from 3.12 to 200 µg/mL, respectively). RSV, RSV-3, and RSV-4 were able to synergize with LVX restoring its effect in two out of seven clinical resistant strains tested for the study. RSV, RSV-3, and RSV-4, alone and with LVX at sub-MIC and sub-synergistic concentrations, significantly reduced the biofilm formation. Moreover, RSV-3 and RSV-4 reduced the H. pylori swarming motility on soft agar. RSV, RSV-3, and RSV-4 were non-toxic for G. mellonella larvae and displayed a protective effect against H. pylori infection. Overall, RSV-phenol derivatives should be considered interesting candidates for innovative therapeutic schemes to tackle the H. pylori antibiotic resistance.
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Affiliation(s)
- Paola Di Fermo
- Department of Pharmacy, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (P.D.F.); (S.D.L.); (R.A.); (B.D.F.); (E.D.C.); (M.D.G.)
| | - Silvia Di Lodovico
- Department of Pharmacy, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (P.D.F.); (S.D.L.); (R.A.); (B.D.F.); (E.D.C.); (M.D.G.)
| | - Rosa Amoroso
- Department of Pharmacy, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (P.D.F.); (S.D.L.); (R.A.); (B.D.F.); (E.D.C.); (M.D.G.)
| | - Barbara De Filippis
- Department of Pharmacy, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (P.D.F.); (S.D.L.); (R.A.); (B.D.F.); (E.D.C.); (M.D.G.)
| | - Simonetta D’Ercole
- Department of Medical Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy;
| | - Emanuela Di Campli
- Department of Pharmacy, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (P.D.F.); (S.D.L.); (R.A.); (B.D.F.); (E.D.C.); (M.D.G.)
| | - Luigina Cellini
- Department of Pharmacy, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (P.D.F.); (S.D.L.); (R.A.); (B.D.F.); (E.D.C.); (M.D.G.)
| | - Mara Di Giulio
- Department of Pharmacy, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (P.D.F.); (S.D.L.); (R.A.); (B.D.F.); (E.D.C.); (M.D.G.)
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Xie Y, Yao Y. Preparation and characterization of a solid dispersion containing curcumin and octenylsuccinate hydroxypropyl phytoglycogen for improved curcumin solubility. Eur J Pharm Sci 2020; 153:105462. [DOI: 10.1016/j.ejps.2020.105462] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 05/10/2020] [Accepted: 07/08/2020] [Indexed: 01/10/2023]
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Xia M, Chen H, Liu S. The synergy of resveratrol and alcohol against Helicobacter pylori and underlying anti-Helicobacter pylori mechanism of resveratrol. J Appl Microbiol 2019; 128:1179-1190. [PMID: 31774610 DOI: 10.1111/jam.14531] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Revised: 11/10/2019] [Accepted: 11/23/2019] [Indexed: 12/13/2022]
Abstract
AIMS To determine individual antibacterial and synergistic antibacterial effects of resveratrol and alcohol against Helicobacter pylori 26695 in vitro, and to elucidate the underlying mechanism of action of resveratrol against H. pylori. METHODS AND RESULTS The minimum inhibitory concentrations (MICs) and time-killing curve of resveratrol and alcohol were determined. Transcriptome analysis by RNA sequencing was used to elucidate the underlying mechanism of action of resveratrol against H. pylori. Our results showed that the MICs of resveratrol and alcohol against H. pylori 26695 are about 64 μg ml-1 and 4% (v/v) respectively. The synergy was found: resveratrol at concentration of 64 μg ml-1 in combination with alcohol at concentration of 4% (v/v) showed >10 000-fold decrease in the mount of viable bacteria compared with resveratrol and alcohol used alone. Transcriptome analysis showed 152 genes were downregulated and 111 genes were upregulated in the presence of resveratrol. Genes involved in protein translation (17·1%), outer membrane proteins (OMPs) (9·9%) and transports (11·2%) comprise 38·2% of the downregulated genes. In comparison, genes involved in redox (13·5%), pathogenesis and motility (9·9%) and iron homeostasis (4·5%) comprise 27·9% of the upregulated genes. CONCLUSIONS The synergy of resveratrol and alcohol against H. pylori was found in this study. The underlying mechanism of action of resveratrol against H. pylori may be mainly attributed to its inhibitory effect on translation, OMPs, transports, ATP synthase and possible oxidative damage. SIGNIFICANCE AND IMPACT OF THIS STUDY Our study provides a global insight into the anti-H. pylori mechanism of resveratrol. Both resveratrol and alcohol can contribute to inhibition of ribosomes, changes in OMPs and oxidative damage, which may be the explanations of synergistic effect against H. pylori elicited by resveratrol and alcohol.
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Affiliation(s)
- M Xia
- Department of Clinical Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - H Chen
- College of Life Science, Sichuan Agricultural University, Ya'an, China
| | - S Liu
- Department of Clinical Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian, China
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Vestergaard M, Ingmer H. Antibacterial and antifungal properties of resveratrol. Int J Antimicrob Agents 2019; 53:716-723. [PMID: 30825504 DOI: 10.1016/j.ijantimicag.2019.02.015] [Citation(s) in RCA: 246] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 02/13/2019] [Accepted: 02/16/2019] [Indexed: 12/30/2022]
Abstract
Resveratrol is a naturally occurring polyphenolic antioxidant that has received massive attention for its potential health benefits, including anticarcinogenesis, anti-aging and antimicrobial properties. The compound is well tolerated by humans and in recent years has been widely used as a nutraceutical. Its common use makes it interesting to investigate with respect to antimicrobial properties both as a single agent and in combination with conventional antibiotics. Resveratrol displays antimicrobial activity against a surprisingly wide range of bacterial, viral and fungal species. At subinhibitory concentrations, resveratrol can alter bacterial expression of virulence traits leading to reduced toxin production, inhibition of biofilm formation, reduced motility and interference with quorum sensing. In combination with conventional antibiotics, resveratrol enhances the activity of aminoglycosides against Staphylococcus aureus, whereas it antagonises the lethal activity of fluoroquinolones against S. aureus and Escherichia coli. Whilst the antimicrobial properties of the compound have been extensively studied in vitro, little is known about its efficacy in vivo. Nonetheless, following topical application resveratrol has alleviated acne lesions caused by the bacterium Propionibacterium acnes. There are currently no in vivo studies addressing its effect in combination with antibiotics, but recent research suggests that there may be a potential for enhancing the antimicrobial efficacy of certain existing antibiotic classes in combination with resveratrol. Given the difficulties associated with introducing new antimicrobial agents to the market, nutraceuticals such as resveratrol may prove to be interesting candidates when searching for solutions for the growing problem of antimicrobial resistance.
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Affiliation(s)
- Martin Vestergaard
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark
| | - Hanne Ingmer
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark.
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Poi WR, Sonoda CK, Amaral MF, Queiroz AF, França AB, Brandini DA. Histological evaluation of the repair process of replanted rat teeth after storage in resveratrol dissolved in dimethyl sulphoxide. Dent Traumatol 2018; 34:254-263. [PMID: 29656537 DOI: 10.1111/edt.12402] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2018] [Indexed: 12/31/2022]
Abstract
BACKGROUND/AIM The storage media is directly related to the prognosis of avulsed teeth, with resveratrol drawing attention due to its antioxidant and anti-inflammatory proprieties. The aim of this study was to evaluate the repair process in rat teeth following delayed replantation after storage in resveratrol (R) dissolved in dimethyl sulphoxide (DMSO). MATERIALS AND METHODS The upper right central incisors of 36 rats were divided into 4 groups. In group I, the teeth were extracted and immediately replanted. Group II teeth were stored in 50 mL R+DMSO (0.0512 g/mL), whereas group III teeth were stored in 50 mL pure DMSO, both for a period of 60 minutes. The teeth of group IV were stored dry for 60 minutes. The teeth of groups II, III and IV were then replanted, and the animals were euthanized after 60 days. Longitudinal histological cuts were HE stained for histomorphometric analysis of the periodontal ligament, alveolar bone, cementum and dentin. RESULTS The analysis of HE stained histological sections showed the following statistical differences: the acute inflammatory process in the epithelial insertion was less prominent in group II than in group III; the organization of the periodontal ligament was better in group I, while the intensity and extension of acute inflammation in the periodontal ligament were better in group I, and worse in group III; the chronic inflammatory infiltrate was less in groups I and IV, and the depth and extent of resorption, as well as the repair of root resorption, were better in group I. CONCLUSIONS Storage in R+DMSO solution did not inhibit root resorption after delayed replantation in rat teeth. It is concluded that pure DMSO is not a suitable transport medium for avulsed teeth.
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Affiliation(s)
- Wilson R Poi
- Surgery and Integrated Clinics, Faculdade de Odontologia, UNESP-Universidade Estadual Paulista, Araçatuba, Brazil
| | - Celso K Sonoda
- Surgery and Integrated Clinics, Faculdade de Odontologia, UNESP-Universidade Estadual Paulista, Araçatuba, Brazil
| | - Marina F Amaral
- Surgery and Integrated Clinics, Faculdade de Odontologia, UNESP-Universidade Estadual Paulista, Araçatuba, Brazil
| | - Alfredo F Queiroz
- Surgery and Integrated Clinics, Faculdade de Odontologia, UNESP-Universidade Estadual Paulista, Araçatuba, Brazil
| | - Alline B França
- Surgery and Integrated Clinics, Faculdade de Odontologia, UNESP-Universidade Estadual Paulista, Araçatuba, Brazil
| | - Daniela A Brandini
- Surgery and Integrated Clinics, Faculdade de Odontologia, UNESP-Universidade Estadual Paulista, Araçatuba, Brazil
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Buommino E, D'Abrosca B, Donnarumma G, Parisi A, Scognamiglio M, Fiorentino A, De Luca A. Evaluation of the antioxidant properties of carexanes in AGS cells transfected with the Helicobacter pylori's protein HspB. Microb Pathog 2017; 108:71-77. [PMID: 28479510 DOI: 10.1016/j.micpath.2017.05.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 04/26/2017] [Accepted: 05/02/2017] [Indexed: 02/07/2023]
Abstract
Naturally derived compounds represent a potential source of pharmacologically active drugs able to contrast different diseases, including gastric cancer, a multifactorial disease, in which the important role played by H. pylori infection has been demonstrated. Carexanes, stilbene derivatives, isolated from plants of the Carex distachya Desf., are unusual secondary metabolites with a tetracyclic skeleton arising from a cyclization of prenylstilbenoid precursors. In this study we firstly showed the ability of three purified carexanes CxB, CxG, and CxI to enhance the antioxidant response of AGS cells and to contrast the effect of the H. pylori's protein HspB. Among them CxI was the molecule that best modified the expression of genes involved in the antioxidant response. In particular, CxI was able to reduce Keap-1 gene expression and induce NQO1 gene expression, both at 4 and 24 h in AGS cells, as showed by real time PCR. Nrf2 induction was evident only at 24 h. Interestingly, the effect of CxI was stronger in HspB-transfected AGS cells, where Keap-1 gene expression was nearly abrogated. Finally, we demonstrated that CxI was able to reduce also COX-2 gene expression in HspB-transfected AGS cells, compared with untreated HspB-transfected cells, both at 4 and 24 h. This study first report that carexanes might represent candidate molecules able to contrast the deleterious effect of HspB protein but also to reduce the inflammatory process induced by H. pylori infection.
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Affiliation(s)
| | - Brigida D'Abrosca
- Department of Environmental Biological and Pharmaceutical Sciences and Technologies, Università degli Studi della Campania Luigi Vanvitelli, 81100 Caserta, Italy
| | - Giovanna Donnarumma
- Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Università degli Studi della Campania Luigi Vanvitelli, Naples, 80138, Italy
| | - Annamaria Parisi
- Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Università degli Studi della Campania Luigi Vanvitelli, Naples, 80138, Italy
| | - Monica Scognamiglio
- Department of Environmental Biological and Pharmaceutical Sciences and Technologies, Università degli Studi della Campania Luigi Vanvitelli, 81100 Caserta, Italy
| | - Antonio Fiorentino
- Department of Environmental Biological and Pharmaceutical Sciences and Technologies, Università degli Studi della Campania Luigi Vanvitelli, 81100 Caserta, Italy
| | - Antonio De Luca
- Department of Mental and Physical Health and Preventive Medicine, Section of Human Anatomy, Università degli Studi della Campania Luigi Vanvitelli, Naples, 80138, Italy
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Zhang X, Jiang A, Qi B, Ma Z, Xiong Y, Dou J, Wang J. Resveratrol Protects against Helicobacter pylori-Associated Gastritis by Combating Oxidative Stress. Int J Mol Sci 2015; 16:27757-69. [PMID: 26610474 PMCID: PMC4661919 DOI: 10.3390/ijms161126061] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 11/09/2015] [Accepted: 11/16/2015] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori (H. pylori)-induced oxidative stress has been shown to play a very important role in the inflammation of the gastric mucosa and increases the risk of developing gastric cancer. Resveratrol has many biological functions and activities, including antioxidant and anti-inflammatory effect. The purpose of this study was to probe whether resveratrol inhibits H. pylori-induced gastric inflammation and to elucidate the underlying mechanisms of any effect in mice. A mouse model of H. pylori infection was established via oral inoculation with H. pylori. After one week, mice were administered resveratrol (100 mg/kg body weight/day) orally for six weeks. The mRNA and protein levels of iNOS and IL-8 were assessed using RT-PCR, Western blot and ELISA. The expression levels of IκBα and phosphorylated IκBα (which embodies the level and activation of NF-κB), Heme Oxygenase-1 (HO-1; a potent antioxidant enzyme) and nuclear factor-erythroid 2 related factor 2 (Nrf2) were determined using Western blot, and lipid peroxide (LPO) level and myeloperoxidase (MPO) activity were examined using an MPO colorimetric activity assay, thiobarbituric acid reaction, and histological-grade using HE staining of the gastric mucosa. The results showed that resveratrol improved the histological infiltration score and decreased LPO level and MPO activity in the gastric mucosa. Resveratrol down-regulated the H. pylori-induced mRNA transcription and protein expression levels of IL-8 and iNOS, suppressed H. pylori-induced phosphorylation of IκBα, and increased the levels of HO-1 and Nrf2. In conclusion, resveratrol treatment exerted significant effects against oxidative stress and inflammation in H. pylori-infected mucosa through the suppression of IL-8, iNOS, and NF-κB, and moreover through the activation of the Nrf2/HO-1 pathway.
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Affiliation(s)
- Xiaolin Zhang
- College of Food and Drug, University of Anhui Science and Technology, Bengbu 233100, China.
| | - Anmin Jiang
- The School of Life Science, University of Science and Technology of China, Hefei 230032, China.
| | - Banghua Qi
- College of Food and Drug, University of Anhui Science and Technology, Bengbu 233100, China.
| | - Zhongyou Ma
- College of Food and Drug, University of Anhui Science and Technology, Bengbu 233100, China.
| | - Youyi Xiong
- College of Food and Drug, University of Anhui Science and Technology, Bengbu 233100, China.
| | - Jinfeng Dou
- College of Food and Drug, University of Anhui Science and Technology, Bengbu 233100, China.
| | - Jianfei Wang
- College of Food and Drug, University of Anhui Science and Technology, Bengbu 233100, China.
- The Ministry of Agriculture Key Laboratory of Microbial Organic Fertilizer, Bengbu 233030, China.
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Zulueta A, Caretti A, Signorelli P, Ghidoni R. Resveratrol: A potential challenger against gastric cancer. World J Gastroenterol 2015; 21:10636-10643. [PMID: 26457023 PMCID: PMC4588085 DOI: 10.3748/wjg.v21.i37.10636] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 07/09/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related mortality in the world. Late diagnosis and classical therapeutic approaches such as surgery, chemotherapy and radiotherapy make this disease a still threatening tumor. Genetic asset, environmental stress, dietary habit and infections caused by Helicobacter pylori (H. pylori) are the major causes concurring to GC initiation. A common mechanism is induction of radicals resulting in gastric mucosal injury. A regular food intake of antioxidant and radical scavenging agents has been proposed to exert protection against tumorigenesis. Resveratrol belongs to the polyphenol flavonoids class of antioxidants produced by a restricted number of plants. Resveratrol exerts bactericidal activity against H. pylori and is a powerful antioxidant, thus acting as a tumor preventive agent. Resveratrol intracellular signaling results in growth arrest and apoptosis, so that it can be directed against tumor progression. Resveratrol therapeutic potential against GC initiation and progression are reviewed here.
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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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Resveratrol against Arcobacter butzleri and Arcobacter cryaerophilus: activity and effect on cellular functions. Int J Food Microbiol 2014; 180:62-8. [PMID: 24786554 DOI: 10.1016/j.ijfoodmicro.2014.04.004] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 04/01/2014] [Accepted: 04/02/2014] [Indexed: 01/24/2023]
Abstract
The frequent isolation of Arcobacter butzleri and Arcobacter cryaerophilus from food samples makes it imperative to search for potential compounds able to inhibit the development of these bacteria. Taking this into consideration, this study focuses on the antimicrobial activity of resveratrol and its mechanism of action against A. butzleri and A. cryaerophilus. The activity of resveratrol was assessed by a microdilution method and time-kill curves. Resveratrol effect on cellular functions was assessed by flow cytometry evaluating intracellular DNA content and metabolic activity. Ethidium bromide (EtBr) accumulation in the presence of resveratrol was also evaluated, as well as the susceptibility to resveratrol in the presence of phenylalanine-arginine β-naphthylamide (PAβN). Scanning electron microscopy (SEM) was used to further evaluate cell damage caused by resveratrol. Resveratrol presented MIC values of 100 and 50μg/mL to A. butzleri and A. cryaerophilus, respectively. Based on the time-kill curves, resveratrol exhibited bactericidal activity, leading to a ≥3log10CFU/mL reduction of initial inoculums, for A. butzleri exponential phase cells incubated for 6h with 1× MIC or with 2× MIC after 24h for stationary phase cells. For A. cryaerophilus cells in exponential growth phase, 99.9% killing was achieved after 24h incubation with 2× MIC, whereas, for stationary phase cells, bactericidal activity was only detected after incubation with 4× MIC. Incubation with resveratrol led to a decrease in both intracellular DNA content and metabolic activity. An increase in the accumulation of EtBr was observed in the presence of resveratrol, and the efflux pump inhibitor PAβN reduced the MIC of resveratrol. SEM analysis revealed disintegration of A. butzleri cells treated with resveratrol, whereas no morphological alteration was observed for A. cryaerophilus cells. Resveratrol has a good anti-Arcobacter activity, and the results obtained suggest that this compound could act through several different mechanisms in the inhibition of this microorganism. The results encourage the use of this compound for the development of potential strategies to control Arcobacter in food products.
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Bisignano C, Filocamo A, La Camera E, Zummo S, Fera MT, Mandalari G. Antibacterial activities of almond skins on cagA-positive and-negative clinical isolates of Helicobacter pylori. BMC Microbiol 2013; 13:103. [PMID: 23659287 PMCID: PMC3654990 DOI: 10.1186/1471-2180-13-103] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2013] [Accepted: 04/26/2013] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Helicobacter pylori is known to be a gastric pathogen of humans. Eradication regimens for H. pylori infection have some side effects, compliance problems, relapses, and antibiotic resistance. Therefore, the need for alternative therapies for H. pylori infections is of special interest. We have previously shown that polyphenols from almond skins are active against a range of food-borne pathogens. The aim of this study was to evaluate the antibacterial effects of natural almond skins before and after simulated human digestion and the pure flavonoid compounds epicatechin, naringenin and protocatechuic acid against H. pylori. RESULTS H. pylori strains were isolated from gastric biopsy samples following standard microbiology procedures. Also, cagA and vacA genes were identified using PCR. Susceptibility studies on 34 strains of H. pylori, including two reference strains (ATCC 43504, ATCC 49503), were performed by the standard agar dilution method. CONCLUSIONS Polyphenols from almond skins were effective in vitro against H. pylori, irrespective of genotype status and could therefore be used in combination with antibiotics as a novel strategy for antibiotic resistance.
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Nawrocki EM, Bedell HW, Humphreys TL. Resveratrol is cidal to both classes of Haemophilus ducreyi. Int J Antimicrob Agents 2013; 41:477-9. [PMID: 23541304 DOI: 10.1016/j.ijantimicag.2013.02.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Revised: 01/30/2013] [Accepted: 02/07/2013] [Indexed: 11/25/2022]
Abstract
Resveratrol, a polyphenolic phytoalexin, is produced by plants in response to infection and has antibacterial activity. Haemophilus ducreyi is a Gram-negative bacterium that is the causative agent of the sexually transmitted disease chancroid. This study employed minimum cidal concentration (MCC) assays to evaluate the potential of resveratrol as a microbicide against H. ducreyi. Five class I and four class II strains of H. ducreyi tested had MCCs ≤500 μg/mL. Resveratrol was also tested against Lactobacillus spp., part of the natural vaginal flora. Representative strains of Lactobacillus were co-cultured with H. ducreyi and 500 μg/mL resveratrol; in all cases, Lactobacillus was recovered in greater numbers than H. ducreyi. These results show that resveratrol is not only bacteriostatic but is bactericidal to H. ducreyi, confirming the compound's potential for use as a topical microbicide to prevent chancroid.
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Affiliation(s)
- Erin M Nawrocki
- Allegheny College Department of Biology, Meadville, PA 16335, USA
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