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Multi-Targeting Carnosic Acid Kills Drug-Resistant Helicobacter pylori With Narrow-Spectrum Activity.

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Title: Multi-Targeting Carnosic Acid Kills Drug-Resistant Helicobacter pylori With Narrow-Spectrum Activity.
Authors: Bai Y; NHC Key Laboratory of Tropical Disease Control, School of Life Sciences and Medical Technology, Hainan Medical University, Haikou, Hainan, China.; Helicobacter Pylori Research Center, Department of Pathogen Biology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.; Institute of Dermatology, Hospital for Skin Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, China., Huang H; NHC Key Laboratory of Tropical Disease Control, School of Life Sciences and Medical Technology, Hainan Medical University, Haikou, Hainan, China., Hang X; NHC Key Laboratory of Tropical Disease Control, School of Life Sciences and Medical Technology, Hainan Medical University, Haikou, Hainan, China., Hu S; Helicobacter Pylori Research Center, Department of Pathogen Biology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China., Tong Q; Helicobacter Pylori Research Center, Department of Pathogen Biology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China., Xu J; Helicobacter Pylori Research Center, Department of Pathogen Biology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China., Jia J; Laboratory of Pathogen Biology, State Key Laboratory of Cardiology and Research Center for Translational Medicine, School of Medicine, Shanghai East Hospital, Tongji University, Shanghai, China.; Key Laboratory of Pathogen-Host Interaction, School of Medicine, Tongji University, Shanghai, China., Bi H; NHC Key Laboratory of Tropical Disease Control, School of Life Sciences and Medical Technology, Hainan Medical University, Haikou, Hainan, China.; Helicobacter Pylori Research Center, Department of Pathogen Biology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
Source: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2026 Sep; Vol. 13 (50), pp. e76080. Date of Electronic Publication: 2026 Jun 11.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE
Imprint Name(s): Original Publication: Weinheim : WILEY-VCH, [2014]-
MeSH Terms: Abietanes*/pharmacology , Abietanes*/therapeutic use , Helicobacter pylori*/drug effects , Helicobacter Infections*/drug therapy , Helicobacter Infections*/microbiology , Anti-Bacterial Agents*/pharmacology , Drug Resistance, Multiple, Bacterial*/drug effects, Biofilms/drug effects ; Animals ; Mice ; Humans ; Disease Models, Animal ; Microbial Sensitivity Tests
Abstract: Helicobacter pylori (H. pylori) is a significant global human pathogen intricately linked to gastritis, peptic ulcers, and gastric cancer. The escalating challenge of antimicrobial resistance and the adverse effects of conventional antibiotics on the gut microbiome necessitate the development of novel, targeted therapeutics. In this study, we demonstrate that carnosic acid (CA), a natural compound derived from traditional Chinese medicine, exhibits potent and specific anti-H. pylori activity in vitro, with no detectable resistance observed after prolonged serial passaging. CA also displayed enhanced antibacterial efficacy under physiologically relevant acidic conditions, correlating with its strong inhibition of urease, a key colonization factor for H. pylori. Beyond urease suppression, CA acted through multiple mechanisms, including inhibiting biofilm formation and disrupting mature biofilms, impairing bacterial motility, and compromising cell membrane integrity. In vivo, the combination of CA and omeprazole achieved superior eradication in a mouse model of multidrug-resistant H. pylori infection compared to standard triple therapy. Furthermore, CA treatment showed negligible toxicity to host tissues and minimal disruption to the diversity and composition of the gut microbiota. These findings position CA as a promising lead compound against drug-resistant H. pylori, offering a multi-targeting and microbiota-friendly strategy to combat this pathogen.
(© 2026 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
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Grant Information: 82473974 National Natural Science Foundation of China; 32470188 National Natural Science Foundation of China; GZC20251367 Postdoctoral Fellowship Program of the China Postdoctoral Science Foundation; 2025M782601 China Postdoctoral Science Foundation; 326QN0613 Hainan Provincial Natural Science Foundation of China; 326QN0606 Hainan Provincial Natural Science Foundation of China; 2025NHCTDC12002 National Health Commission Key Laboratory of Tropical Disease Control of China; 2026NHCTDC12004 National Health Commission Key Laboratory of Tropical Disease Control of China; XSTS2026115 Academic Improvement Support Program of Hainan Medical University of China; XSTS2026003 Academic Improvement Support Program of Hainan Medical University of China
Contributed Indexing: Keywords: Helicobacter pylori; carnosic acid; mode of action; narrow‐spectrum activity
Substance Nomenclature: 0 (Abietanes)
LI791SXT24 (salvin)
0 (Anti-Bacterial Agents)
Entry Date(s): Date Created: 20260611 Date Completed: 20260907 Latest Revision: 20260907
Update Code: 20260907
PubMed Central ID: PMC13336857
DOI: 10.1002/advs.76080
PMID: 42272345
Database: MEDLINE
Description
ISSN:2198-3844
DOI:10.1002/advs.76080