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

Abstract

With the widespread use and abuse of antibiotics, Helicobacter pylori (H. pylori) has become seriously drug resistant. The development of new antibiotics is an important way to solve H. pylori'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 minimal inhibitory concentration (MIC) for 18 H. pylori strains was 16–32 μg/ml. The minimum bactericidal concentration (MBC) of H. pylori G27 was 128 μg/ml; the higher the drug concentration and the longer the time, the better the sterilization effect. It was non-toxic to gastric epithelial cell (GES)-1 and BGC823 cells at the concentration of 100 μg/ml. It presented a better antibacterial effect on H. pylori in an acidic environment, and after 24 days of induction on H. pylori with 1/4 MIC of phillygenin, no change was found in the MIC of H. pylori. In the mechanism of action, phillygenin could cause ATP leakage and inhibit the biofilm formation; the latter 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 H. pylori's acid resistance and virulence, the diminishing of H. pylori's capacity for drug efflux, H. pylori's DNA methylation, the initiation of human immune response, and the ATP leakage of H. pylori, thus accelerating the death of H. pylori. In conclusion, phillygenin was a main ingredient inhibiting H. pylori in Forsythia suspensa, with a good antibacterial activity, high safety, strong specificity, better antibacterial effect under acidic conditions, and low risk of resistance development by H. pylori. Its mechanism of action was mainly associated with inhibiting the biofilm formation and resulting in ATP leakage. In addition, phillygenin was shown to be able to reduce the acid resistance and virulence of H. pylori.

Hotspots and frontiers in Helicobacter pylori biofilm research: A bibliometric and visualization analysis from 1998 to 2023

“…The relationship between H. pylori biofilm formation and antibiotic resistance requires further study. In addition, new drugs for H. pylori biofilm intervention have recently emerged, such as nanomaterials, Chinese herbal extracts, and probiotics [ [40] , [41] , [42] , [43] , [44] , [45] ], but the mechanism by which they reduce H. pylori biofilm formation is not clear.…”

Global trends of Helicobacter pylori biofilm research in the past two decades: A bibliometric study

“…37 In addition, new drugs for helicobacter pylori bio lm intervention have emerged in large numbers recently, such as nanomaterials, chinese herbal extracts, probiotics, etc. [38][39][40][41][42] Helicobacter bio lm remained a niche eld of study. More and more study occurred in recent 5 years, although its IF was not high, it is meaningful for long-term academic development in the future.…”

The Potential of Alternative Therapies and Vaccine Candidates against Helicobacter pylori

“…Overall, 10 categories of antibacterial mechanism were examined in the studies: (1) antibiofilm, (2) anti-urease, (3) gastroprotection, (4) anti-inflammation, (5) effect on H. pylori virulence factors, (6) ATP leakage from H. pylori, (7) immune response, (8) H. pylori conversion from spiral to coccoid (inactive form), (9) cellular signaling, and (10) bacterial burden. Two studies found that the ethyl acetate fraction from Hibiscus rosa-sinensis red flower [29] and phylligenin, a compound isolated from flowering plant Forsythia [37], exhibited anti-biofilm activity against H. pylori. Meanwhile, four studies found that natural plant products possessed anti-urease activity, and six studies showed the gastroprotective properties of plant natural products.…”

“…Two studies each demonstrated a reduction in cellular signaling important in H. pylori-induced carcinogenesis [30,48] and conversion of H. pylori from the active (spiral) to inactive coccoid form [29,42]. Li et al [37] observed that phylligenin extracted from Forsythia induced ATP leakage in H. pylori and inhibited the mechanism of antibacterial resistance in the bacteria, as well as induced a good immune response.…”