Antibacterial Activity of Alginate-Silver-S-Nitrosoglutathione Nanoparticle Gel in Treatment of Helicobacter Pylori Infected Mouse Model

doi:10.3870/j.issn.1672-8009.2026.01.004

Abstract

Abstract: Objective To investigate the antibacterial activity of alginate-silver-S-nitrosoglutathione nanoparticle(NP) gel in the treatment of Helicobacter pylori(H.pylori)infected mouse model. Methods Alginate NPs gel,alginate-Ag NPs gel and alginate-Ag-GSNO NPs gel were prepared.The surface characteristics of Ag-GSNO nanoparticle gel were imaged by scanning electron microscopy.A mouse model of H.pylori infection was established.A total of 40 male C57BL/6 mice were randomly divided into 4 groups with 10 mice each:Vehicle group,Model group,Alginate-Ag NPs gel group,Alginate-AG-GSNO NPs gel group.The colony forming unit(CFU)counting of H.pylori infection in mice gastric epithelium was performed with blood agar culture.HE staining and histopathology were used to analyze the inflammation and injury of gastric epithelium in mice.The expression levels of ureB gene,which is a positive marker of H.pylori infection,was determined by qPCR.The levels of inflammatory cytokines TNF-α,IL-1β and IL-6 were determined by ELISA.The expression levels of NLRP3 inflammasome was determined by Westren blotting. Results Alginate-Ag nanoparticles had a spherical morphology,with a particle size range of 100-200 nm.Spray dried GSNO particles were spherical with slight depressions,and their size was at the μm level.Compared with those in the Alginate-Ag NPs gel group,the CFU of H.pylori infected mice gastric epithelial tissues was decreased(P<0.05),and the HE staining score was reduced(P<0.05)in the Alginate-AG-GSNO NPs gel group.The Gastric epithelial cells in the Alginate-AG-GSNO NPs gel group were arranged orderly in the Alginate-AG-GSNO NPs gel group,and there were a reduced number of polymorphonuclear infiltration,lymphoid aggregation and H.pylori infection positive cells,indicating the improvement of inflammation and injury of gastric epithelial tissues.The expression levels of ureB gene,the relative expression levels of NLRP3 inflammasome,and the levels of inflammatory cytokines TNF-α,IL-1β and IL-6 were all decreased(all P<0.05). Conclusion Compared with alginate-Ag NPs gel,alginate-AG-GSNO NPs gel could more effectively inhibit the colonization of H.pylori in infected mouse model and improve gastric epithelium damage.

Key words: Helicobacter pylori, alginate-Ag nanoparticles gel, alginate-Ag-GSNO nanoparticles gel, gastric epithelial tissue, antibacterial activity

CLC Number:

Kasimu Kahaer, Ayinuer Tuluhong, Adili Abudureheman. Antibacterial Activity of Alginate-Silver-S-Nitrosoglutathione Nanoparticle Gel in Treatment of Helicobacter Pylori Infected Mouse Model[J]. Journal of Medical Molecular Biology, 2026, 23(1): 27-35.

References

[1] BRAY F,LAVERSANNE M,SUNG H,et al.Global cancer statistics 2022:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2024,74(3):229-263.
[2] LI Y,CHOI H,LEUNG K,et al.Global prevalence of Helicobacter pylori infection between 1980 and 2022:a systematic review and meta-analysis[J].Lancet Gastroenterol Hepatol,2023,8(6):553-564.
[3] KUO C J,LEE C H,CHANG M L,et al.Multidrug resistance:The clinical dilemma of refractory Helicobacter pylori infection[J].J Microbiol Immunol Infect,2021,54(6):1184-1187.
[4] 朱晓.分阶段三联疗法联合益生菌对幽门螺旋杆菌胃炎患者的效果及其对COX-2和E-cadherin的影响[J].川北医学院学报,2024,39(5):692-695.
ZHU X.Study on the effect of phased triple therapy combined with probiotics in patieuts with Helicobacter pylori gastribis and its impact on COX-2 and E-cadherin[J].J North Sichuan Med Coll,2024,39(5):692-695.
[5] DANAI L,ROLBAND L A,PERDOMO V A,et al.Optical,structural and antibacterial properties of silver nanoparticles and DNA-templated silver nanoclusters[J].Nanomedicine,2023,18(9):769-782.
[6] YANG L,FEURA E S,AHONEN M J R,et al.Nitric oxide-releasing macromolecular scaffolds for antibacterial applications[J].Adv Healthc Mater,2018,7(13):e1800155.
[7] MCKINSEY M G,BATE M Y,TRAMONTE L M,et al.Regulation of Helicobacter pylori urease and acetone carboxylase genes by nitric oxide and the CrdRS two-component system[J].Microbiol Spectr,2023,11(1):e04633-22.
[8] PAPAEFTHYMIOU A,DOULBERIS M,KATSINELOS P,et al.Impact of nitric oxide’s bidirectional role on glaucoma:Focus on Helicobacter pylori-related nitrosative stress[J].Ann N Y Acad Sci,2020,1465(1):10-28.
[9] HU X,LI Y,CAO Y,et al.The role of nitric oxide synthase/nitric oxide in infection-related cancers:Beyond antimicrobial activity[J].Biochim Biophys Acta Rev Cancer,2024,1879(5):189156.
[10] URZEDO A L,GONÇALVES M C,NASCIMENTO M H M,et al.Multifunctional alginate nanoparticles containing nitric oxide donor and silver nanoparticles for biomedical applications[J].Mater Sci Eng C Mater Biol Appl,2020,112:110933.
[11] DOUGLASS M,HOPKINS S,PANDEY R,et al.S-nitrosoglutathione-based nitric oxide-releasing nanofibers exhibit dual antimicrobial and antithrombotic activity for biomedical applications[J].Macromol Biosci,2021,21(1):e2000248.
[12] DOUGLASS M E,GOUDIE M J,PANT J,et al.Catalyzed nitric oxide release via Cu nanoparticles leads to an increase in antimicrobial effects and hemocompatibility for short term extracorporeal circulation[J].ACS Appl Bio Mater,2019,2(6):2539-2548.
[13] PUCCETTI M,DONNADIO A,RICCI M,et al.Alginate Ag/AgCl nanoparticles composite films for wound dressings with antibiofilm and antimicrobial activities[J].J Funct Biomater,2023,14(2):84.
[14] FAN Y,LIAO C,LI J,et al.S-nitrosoglutathione releasing nano-micron combination hydrogel enhances cutaneous wound healing via promoting angiogenesis and collagen deposition[J].J Drug Target,2025,33(8):1412-1420.
[15] FITZGERALD R,SMITH S M.An overview of Helicobacter pylori infection[J].Methods Mol Biol,2021,2283:1-14.
[16] BRUNA T,MALDONADO-BRAVO F,JARA P,et al.Silver nanoparticles and their antibacterial applications[J].Int J Mol Sci,2021,22(13):7202.
[17] BALU S K,ANDRA S,DAMIRI F,et al.Size-dependent antibacterial,antidiabetic,and toxicity of silver nanoparticles synthesized using solvent extraction of Rosa indica L.petals[J].Pharmaceuticals,2022,15(6):689.
[18] JUSTINO M C,PARENTE M R,BONECA I G,et al.FrxA is an S-nitrosoglutathione reductase enzyme that contributes to Helicobacter pylori pathogenicity[J].FEBS J,2014,281(19):4495-4505.
[19] AHONEN M J,SUCHYTA D J,ZHU H,et al.Nitric oxide-releasing alginates[J].Biomacromolecules,2018,19(4):1189-1197.
[20] DHAMECHA D,MOVSAS R,SANO U,et al.Applications of alginate microspheres in therapeutics delivery and cell culture:Past,present and future[J].Int J Pharm,2019,569:118627.
[21] AGÜERO L,ZALDIVAR-SILVA D,PEÑA L,et al.Alginate microparticles as oral colon drug delivery device:A review[J].Carbohydr Polym,2017,168:32-43.
[22] HURTADO A,ALJABALI A A A,MISHRA V,et al.Alginate:enhancement strategies for advanced applications[J].Int J Mol Sci,2022,23(9):4486.
[23] SHAH S U,SOCHA M,FRIES I,et al.Synthesis of S-nitrosoglutathione-alginate for prolonged delivery of nitric oxide in intestines[J].Drug Deliv,2016,23(8):2927-2935.
[24] RAZMJOOEE K,OUSTADI F,GOLAGHAEI A,et al.Carboxymethyl chitosan-alginate hydrogel containing GSNO with the ability to nitric oxide release for diabetic wound healing[J].Biomed Mater,2022,17(5).DOI:10.1088/1748-605 X/ac877 c.
[25] TSAY F W,HSU P I.H.pylori infection and extra-gastroduodenal diseases[J].J Biomed Sci,2018,25(1):65.
[26] BALENDRA V,AMOROSO C,GALASSI B,et al.High-salt diet exacerbates H.pylori infection and increases gastric cancer risks[J].J Pers Med,2023,13(9):1325.
[27] EL KHADIR M,ALAOUI BOUKHRIS S,BENAJAH D A,et al.Detection of Helicobacter pylori urease antigen in saliva in patients with different gastric H.pylori status[J].J Chin Med Assoc,2016,79(7):363-367.
[28] 常明珠,李雨澎,母润红,等.幽门螺旋杆菌检测方法及其应用价值的研究进展[J].吉林大学学报(医学版),2023,49(1):253-260.
CHANG M Z,LI Y P,MUR H,et al.Research progress in detection methosd of Hrlicobacter pylori and application values[J].J Jilin Univ(Med Ed),2023,49(1):253-260.
[29] ZHANG X,LI C,CHEN D,et al.H.pylori CagA activates the NLRP3 inflammasome to promote gastric cancer cell migration and invasion[J].Inflamm Res,2022,71(1):141-155.