浒苔多糖对幽门螺杆菌活性抑制作用研究OA

Helicobacter pylori is a Gram-negative,microaerophilic bacterium that selectively colonizes the gastric mucosa of humans,establishing infections that can persist for decades in the absence of targeted intervention.As a Group 1 carcinogen officially classified by the World Health Organization(WHO),H.pylori infection is recognized globally as a pivotal etiological factor in the pathogenesis of a spectrum of gastric disorders,ranging from mild chronic gastritis and recurrent peptic ulcers to life-threatening conditions,including gastric mucosa-associated lymphoid tissue(MALT)lymphoma and gastric adenocarcinoma,which account for a substantial proportion of gastrointestinal cancer-related mortalities worldwide.The unique ability of this pathogen to thrive in the highly acidic milieu of the stomach is primarily attributed to the secretion of urease,a key virulence enzyme that catalyzes the hydrolysis of endogenously-available urea into ammonia and carbon dioxide.This metabolic process effectively neutralizes the surrounding gastric acid,creating a microenvironment conducive to bacterial adhesion,colonization,and long-term persistence.Despite the availability of standard antibiotic-based eradication regimens(e.g.,proton pump inhibitor triple therapy),the escalating global prevalence of antimicrobial resistance—driven by inappropriate antibiotic use and inadequate treatment compliance—has substantially compromised the clinical efficacy of these therapies,with eradication rates declining to suboptimal levels in many regions.This growing challenge makes alternative therapeutic strategies imperative,particularly those derived from natural sources with novel mechanisms of action that can circumvent existing resistance pathways and mitigate the burden of H.pylori-associated diseases. Marine macroalgae have emerged as rich reservoirs of bioactive compounds with diverse pharmacological properties.Of these,Ulva prolifera,a nutrient-rich green alga that is abundantly distributed in coastal regions worldwide,has attracted considerable research interest due to its rapid growth,ease of cultivation,and potential for resource utilization.Polysaccharides extracted from U.prolifera,referred to as U.prolifera polysaccharides(UPPs),are considered the principal bioactive constituents and have been reported to exhibit a wide array of biological activities,including antioxidant,immunomodulatory,anti-inflammatory,and antimicrobial effects.Despite growing evidence supporting the antibacterial properties of UPPs against various pathogens,their specific activity against H.pylori and the underlying mechanisms are unclear. The fundamental structural features of UPPs were characterized and in vitro inhibitory effects against H.pylori were evaluated.HPLC and FTIR analyses revealed that UPPs are heteropolysaccharides composed mainly of glucose,rhamnose,glucuronic acid,and xylose.UPPs are acidic polysaccharides enriched with negatively-charged functional groups with a total uronic acid content of 10.84％.The presence of uronic acid contributes to the polyanionic nature of UPPs,which may facilitate electrostatic interactions with positively-charged components on the bacterial cell surface,thereby promoting membrane disruption and enhancing antibacterial activity.The antibacterial efficacy of UPPs against H.pylori was assessed using a combination of the MTT assay and the dilution plating method.UPPs exerted a concentration-dependent inhibitory effect on bacterial growth.At a concentration of 40 mg/mL,UPPs exhibited potent antibacterial activity,with inhibition rates of 67.68％±2.37％.UPPs possess an anti-H.pylori potential,warranting further investigation into their mechanisms of action. To elucidate the mechanism of UPP-mediated inhibition,the effects of UPPs on urease activity,a key virulence determinant essential for H.pylori colonization and survival in the gastric niche,were investigated.Treatment with UPPs markedly reduced the relative urease content of H.pylori,suggesting that UPPs interfere with bacterial colonization capacity by suppressing urease production or activity.This reduction in urease levels likely compromises the ability of H.pylori to neutralize the gastric acidity,thereby rendering the bacterium more susceptible to hostile gastric environment.Morphological observations using transmission electron microscopy provided visual evidence of UPP-induced structural damage in H.pylori cells.Following exposure to UPPs,bacterial cells exhibited severe morphological alterations,including cell membrane disruption,loss of cellular integrity,and leakage of intracellular contents.These ultrastructural changes indicate irreversible cell damage and suggest that UPPs exert their antibacterial effects,at least in part,by targeting the bacterial cell envelope,leading to osmotic imbalance and eventual cell death. Polysaccharides derived from U.prolifera exhibited substantial inhibitory activity in vitro against H.pylori through a dual mechanism involving the reduction of urease-mediated colonization capacity and the direct disruption of bacterial cell membrane integrity.These findings elucidate the antibacterial properties of marine algal polysaccharides and highlight the potential of UPPs as candidates for the development of novel,natural antibacterial agents targeting H.pylori-associated gastric diseases.Given the increasing global burden of antibiotic resistance,the exploitation of marine-derived bioactive compounds such as UPPs represents a valuable strategy for the discovery of alternative therapeutic agents.Future studies should focus on elucidating the structure-activity relationships of UPPs,optimizing extraction and purification protocols,and evaluating their in vivo efficacy and safety in appropriate animal models to facilitate their eventual clinical application.