Academic Journal
Mechanistic insights into Helicobacter pylori urease inhibition by poplar propolis ethanol extract.
| Title: | Mechanistic insights into Helicobacter pylori urease inhibition by poplar propolis ethanol extract. |
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| Authors: | Yuan J; College of Agriculture and Biology, Liaocheng University, Liaocheng, People's Republic of China; Institut for Advanced Studies, Universiti Malaya, Kuala Lumpur, Malaysia., Li T; College of Agriculture and Biology, Liaocheng University, Liaocheng, People's Republic of China., Gao S; College of Agriculture and Biology, Liaocheng University, Liaocheng, People's Republic of China., Tang Y; College of Agriculture and Biology, Liaocheng University, Liaocheng, People's Republic of China., Ma S; College of Agriculture and Biology, Liaocheng University, Liaocheng, People's Republic of China., Lee HY; Tropical Infectious Diseases Research and Education Centre, Universiti Malaya, Kuala Lumpur, Malaysia. Electronic address: leehaiyen@um.edu.my., Chin KL; Institut for Advanced Studies, Universiti Malaya, Kuala Lumpur, Malaysia; Department of Medical Microbiology, Universiti Malaya, Kuala Lumpur, Malaysia. Electronic address: chinkimling@um.edu.my., Xuan H; College of Agriculture and Biology, Liaocheng University, Liaocheng, People's Republic of China. Electronic address: xuanhongzhuan@lcu.edu.cn. |
| Source: | Journal of ethnopharmacology [J Ethnopharmacol] 2026 Jun 28; Vol. 365, pp. 121596. Date of Electronic Publication: 2026 Mar 28. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Sequoia Country of Publication: Ireland NLM ID: 7903310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7573 (Electronic) Linking ISSN: 03788741 NLM ISO Abbreviation: J Ethnopharmacol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Limerick : Elsevier Sequoia Original Publication: Lausanne, Elsevier Sequoia. |
| MeSH Terms: | Urease*/antagonists & inhibitors , Urease*/metabolism , Urease*/genetics , Propolis*/pharmacology , Propolis*/chemistry , Helicobacter pylori*/drug effects , Helicobacter pylori*/enzymology , Helicobacter pylori*/growth & development , Plant Extracts*/pharmacology , Plant Extracts*/chemistry , Anti-Bacterial Agents*/pharmacology , Anti-Bacterial Agents*/isolation & purification , Anti-Bacterial Agents*/chemistry , Populus*/chemistry , Enzyme Inhibitors*/pharmacology, Ethanol/chemistry ; Molecular Docking Simulation |
| Abstract: | Ethnopharmacological Relevance: Propolis, a resinous mixture from plant exudates, is widely used in traditional ethnomedicine for gastrointestinal infections, implying anti-Helicobacter pylori (H. pylori) potential. However, its molecular mechanisms targeting H. pylori urease (HPU), a key virulence factor, remain unclear. Aim of the Study: This study aimed to characterize the inhibitory activity and kinetic properties of poplar propolis ethanol extract (PPEE) against HPU and jack bean urease (JBU), and to elucidate the underlying molecular mechanisms. Materials and Methods: UPLC-MS/MS-based metabolomics was used to identify PPEE's potential bioactive candidates. Enzyme activity assays, kinetic analysis, thiol/Ni2+ protection assays, transcriptional profiling of urease-related genes, and molecular docking were applied for mechanistic exploration. Bacterial growth curve assays and PI staining verified its antibacterial activity. Results: PPEE, enriched in flavonoids and phenolic acids, exhibited significant dose-dependent and reversible inhibition on HPU, with superior potency to JBU. Mechanistically, PPEE acted synergistically by competitively binding to HPU's substrate pocket, disrupting thiol-Ni2+ coordination, inducing slow-binding conformational stabilization, and perturbing tertiary structure. It also downregulated ureA/ureB, nixA, and ureH/ureI, forming a multi-layered mode of "direct enzyme inhibition + blocking synthesis/assembly". Urease inhibition was the core anti-H. pylori mechanism, with auxiliary urease-independent activity. Molecular docking confirmed stable interactions between PPEE components and HPU's active center/substrate pocket. Experimental validation showed that quercetin and taxifolin inhibited HPU in a dose-dependent manner. Conclusions: PPEE specifically inhibits HPU via multi-targeted synergistic mechanisms, providing molecular evidence for propolis-derived anti-H. pylori agents and laying a foundation for subsequent SAR and in vivo studies. (Copyright © 2026 Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Helicobacter pylori; Kinetics; Molecular docking; Propolis ethanol extract; Urease |
| Substance Nomenclature: | EC 3.5.1.5 (Urease) 9009-62-5 (Propolis) 0 (Plant Extracts) 0 (Anti-Bacterial Agents) 3K9958V90M (Ethanol) 0 (Enzyme Inhibitors) |
| Entry Date(s): | Date Created: 20260330 Date Completed: 20260713 Latest Revision: 20260714 |
| Update Code: | 20260714 |
| DOI: | 10.1016/j.jep.2026.121596 |
| PMID: | 41911984 |
| Database: | MEDLINE |
| ISSN: | 1872-7573 |
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| DOI: | 10.1016/j.jep.2026.121596 |