Synergistic potentiation of antibiotics by chamomile phytochemicals against multidrug-resistant Helicobacter pylori.

Abstract

Background: Helicobacter pylori is a significant global health issue, infecting nearly half of the population. Increasing antibiotic resistance leads to treatment failures. This study examined the antibacterial effects of chamomile ethanolic extract, both alone and combined with standard antibiotics, as a potential approach to fighting antibiotic-resistant H. pylori strains.

Methods: Thirty antral gastric biopsies were collected from patients undergoing diagnostic upper endoscopy at El-Demerdash Hospital in Cairo, Egypt. H. pylori isolates were identified by rapid urease test (RUT), cultured, and tested for antimicrobial susceptibility to clarithromycin (CLR, 15 µg), metronidazole (MET, 5 µg), amoxicillin (AX, 25 µg), tetracycline (TE, 30 µg), rifampicin (RA, 30 µg), and levofloxacin (LEV, 5 µg). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. The antibacterial activity of chamomile ethanolic extract was tested alone and in combination with these antibiotics. Phytochemical profiling was conducted using FT-IR and GC-MS. The identified compounds were analyzed through molecular docking against ten H. pylori targets: lipoprotein 20 (LPP20, HP1456), aspartate α-decarboxylase (ADC), S-ribosylhomocysteinase (LuxS), GTP cyclohydrolase II (GCH II), cytotoxin-associated gene A (CagA), sialic acid-binding adhesin (SabA), blood group antigen-binding adhesin (BabA), vacuolating cytotoxin A (VacA), and fructose-1,6-bisphosphate aldolase (FBA), using AutoDock Vina 1.5.7.

Results: All thirty biopsies tested positive for RUT, although only 20 yielded successful cultures. The chamomile ethanolic extract demonstrated anti-H. pylori activity against all 20 isolates, with MIC values ranging from 1.562 to 6.25 mg/mL and MBC values from 3.12 to 12.5 mg/mL. When combined with antibiotics, the extract altered their antibacterial activity, primarily producing synergistic effects, while a few combinations exhibited antagonistic effects. Notably, in cases where antibiotics alone had limited activity, adding chamomile extract significantly enhanced effectiveness, increasing inhibition zones by 2.2-fold for tetracycline, 2.1-fold for rifampicin, and 1.7-2.3-fold for levofloxacin. FT-IR analysis confirmed the chemical safety of the extract, while GC-MS profiling identified 38 constituents, including 14 compounds with known antimicrobial properties. Molecular docking revealed strong binding affinities of eight bioactive compounds toward H. pylori target proteins. Additionally, Lipinski's Rule of Five and ADMET profiling indicated these compounds possess favorable drug-like properties, including safety and oral bioavailability.

Conclusions: Chamomile ethanolic extract shows promising anti-H. pylori activity and can enhance the effectiveness of standard antibiotics, indicating its potential as a complementary treatment to combat antibiotic-resistant H. pylori infections.