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Luteolin as a urease inhibitor: A novel therapeutic strategy against Helicobacter pylori.

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Τίτλος: Luteolin as a urease inhibitor: A novel therapeutic strategy against Helicobacter pylori.
Συγγραφείς: Wang X; College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China., Zhou D; Jiangxi Province Key Laboratory of Traditional Chinese Medicine Pharmacology, Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang, China.; Jiangxi Health Industry Institute of Traditional Chinese Medicine, Nanchang, China., Li M; College of Integrated Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, China., Kong X; Endocrinology Department, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China., Jiang S; School of Basic Medicine, Changchun University of Chinese Medicine, Changchun, China., Li Q; Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China., Wei L; School of Basic Medicine, Changchun University of Chinese Medicine, Changchun, China., Jiang L; College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China., Song W; School of Basic Medicine, Changchun University of Chinese Medicine, Changchun, China.
Πηγή: Virulence [Virulence] 2026 Dec; Vol. 17 (1), pp. 2712031. Date of Electronic Publication: 2026 Aug 03.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101531386 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-5608 (Electronic) Linking ISSN: 21505594 NLM ISO Abbreviation: Virulence Subsets: MEDLINE
Imprint Name(s): Publication: 2015- : Philadelphia, PA : Taylor & Francis
Original Publication: Austin, Tex. : Landes Bioscience
Ιατρικοί όροι (MeSH): Luteolin*/pharmacology , Urease*/antagonists & inhibitors , Urease*/chemistry , Helicobacter pylori*/drug effects , Helicobacter pylori*/enzymology , Helicobacter Infections*/drug therapy , Helicobacter Infections*/microbiology , Enzyme Inhibitors*/pharmacology , Anti-Bacterial Agents*/pharmacology, Bacterial Proteins/antagonists & inhibitors ; Animals ; Mice ; Humans ; Molecular Docking Simulation ; Cell Line ; Disease Models, Animal
Περίληψη: The rising prevalence of antibiotic-resistant Helicobacter pylori (H. pylori) underscores the urgent need for alternative treatment strategies. By producing ammonia to neutralize gastric acid, the key virulence factor urease is essential for H. pylori acid tolerance, thereby representing a promising therapeutic target. In this study, we identified luteolin as a potent urease inhibitor (IC50 = 30.50 μg/mL) from a screening of over 200 natural compounds. Further investigation through molecular docking, dynamics simulations, cellular thermal shift assay, and enzyme kinetics studies confirmed its competitive binding to the Ni2+-centered catalytic site of H. pylori urease (HPU). Luteolin exhibited potent anti-H. pylori activity under standard and simulated gastric conditions, and showed low propensity for resistance development over 14 serial passages. Proteomic and metabolomic analyses revealed that luteolin inhibited HPU activity, and the consequent ammonia restriction triggered severe metabolic dysfunction, characterized by disruptions in nucleotide, amino acid biosynthesis and TCA cycle. In GES-1 cells, luteolin protected against H. pylori-induced damage. In a mouse model of H. pylori-induced peptic ulcer, luteolin treatment significantly reduced the bacterial load, with concomitant alleviation of gastric mucosal pathology and suppression of inflammatory responses. In contrast to antibiotic-induced gastric microbial dysbiosis, microbial diversity analysis indicated that luteolin treatment had minimal impact on the resident gastric microbiota. In summary, as a urease inhibitor, luteolin suppresses H. pylori by blocking ammonia production, thereby disrupting acid neutralization and inducing metabolic dysfunction, which collectively alleviates gastric damage and inflammation while minimizing microbiota disruption and resistance risk.
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Contributed Indexing: Keywords: Helicobacter pylori; ammonia restriction; luteolin; metabolic disruption; urease
Substance Nomenclature: KUX1ZNC9J2 (Luteolin)
EC 3.5.1.5 (Urease)
0 (Enzyme Inhibitors)
0 (Anti-Bacterial Agents)
0 (Bacterial Proteins)
Entry Date(s): Date Created: 20260804 Date Completed: 20260804 Latest Revision: 20260813
Update Code: 20260814
PubMed Central ID: PMC13449824
DOI: 10.1080/21505594.2026.2712031
PMID: 42548046
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2150-5608
DOI:10.1080/21505594.2026.2712031