AUTHOR=Li Ru-Jia , Qin Chun , Huang Gan-Rong , Liao Li-Juan , Mo Xiao-Qiang , Huang Yan-Qiang 

TITLE=Phillygenin Inhibits Helicobacter pylori by Preventing Biofilm Formation and Inducing ATP Leakage

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.863624

DOI=10.3389/fmicb.2022.863624

ISSN=1664-302X

ABSTRACT=With the widespread use and abuse of antibiotics, Helicobacter pylori (H. pylori, Hp) has become seriously drug-resistant. The development of new antibiotics is an important way to solve Hp’s drug resistance. Screening antibacterial ingredients from natural products is a convenient way to develop new antibiotics. Phillygenin, an effective antibacterial component, was selected from the natural product-forsythia in this study. Its MIC (minimal inhibitory concentration) for 18 Hp strains  was 16-32g/mL, and the MBC (minimum bactericidal concentration) of G27  was 128g/mL, with the effect presenting concentration and time-dependent changes and reached; it was non-toxic to GES-1 and BGC823 cells at the concentration of 100g/mL; it presented a better antibacterial effect on Hp in an acidic environment; after 24 days of induction on Hp with 1/4 MIC of Phillygenin, no change was found in the MIC of Hp. In the mechanism of action, Phillygenin could cause ATP leakage  in a concentration-dependent manner; inhibit the formation of Hp’s biofilm, and its mechanism was associated with the regulation of spoT and Hp1174 genes; in addition, Phillygenin could regulate the genes of Nhac, caggamma, MATE, MdoB, flagellinA, and lptB, leading to the weakening of Hp’s acid resistance and virulence, the diminishing of Hp’s capacity for drug efflux, Hp’s DNA methylation, the initiation of human immune response and the ATP leakage of Hp, thus accelerating the death of Hp. In conclusion, Phillygenin was main ingredient for inhibiting Hp in forsythia, with a good antibacterial activity, high safety, strong specificity, better antibacterial effect under acidic conditions, difficulty making Hp develop a drug resistance. Its mechanism of action was mainly associated with helping inhibit the biofilm formation of Hp and resulting in its ATP leakage. In addition, Phillygenin was shown to be able to reduce the acid resistance and virulence of Hp, It has the characteristics of multitargeted drugs.