1,3,6-Trigalloylglucose: A Novel Potent Anti-Helicobacter pylori Adhesion Agent Derived from Aqueous Extracts of Terminalia chebula Retz.

1,3,6-Trigalloylglucose is a natural compound that can be extracted from the aqueous extracts of ripe fruit of Terminalia chebula Retz, commonly known as "Haritaki". The potential anti-Helicobacter pylori (HP) activity of this compound has not been extensively studied or confirmed in scientific research. This compound was isolated using a semi-preparative liquid chromatography (LC) system and identified through Ultra-high-performance liquid chromatography-MS/MS (UPLC-MS/MS) and Nuclear Magnetic Resonance (NMR). Its role was evaluated using Minimum inhibitory concentration (MIC) assay and minimum bactericidal concentration (MBC) assay, scanning electron microscope (SEM), inhibiting kinetics curves, urea fast test, Cell Counting Kit-8 (CCK-8) assay, Western blot, and Griess Reagent System. Results showed that this compound effectively inhibits the growth of HP strain ATCC 700392, damages the HP structure, and suppresses the Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Importantly, it exhibits selective antimicrobial activity without impacting normal epithelial cells GES-1. In vitro studies have revealed that 1,3,6-Trigalloylglucose acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, a critical step in HP infection. These findings underscore the potential of 1,3,6-Trigalloylglucose as a targeted therapeutic agent against HP infections.

Studies on the mechanisms of Helicobacter pylori inhibition by Syzygium aromaticum aqueous extract.

BACKGROUND: The aqueous extract of the dried buds of Syzygium aromaticum (SAAE) have the potential to alleviate Helicobacter pylori infection, but the specific molecular mechanism has not been fully elucidated. PURPOSE: This study aimed to investigate the underlying mechanisms of SAAE on H. pylori pathogenicity. METHODS: The inhibitory kinetics and anti-H. pylori adhesive capacity assays were conducted to examine the effects of SAAE on the growth and adhesive capability of H. pylori. The H. pylori outer membrane vesicles (OMVs) were purified from the culture supernatant through high-speed centrifugation, filtration, and two rounds of ultracentrifugation. Their characteristics and protein composition were then identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and qualitative proteomics study. Subsequently, the effect of SAAE on the pathogenicity of H. pylori OMVs was investigated using the Griess reagent assay, enzyme-linked immunosorbent assay (ELISA), quantitative proteomics study, TEM, and western blotting assay. RESULTS: SAAE exhibited inhibitory effects on H. pylori growth and adhesion. The isolated H. pylori OMVs showed particle size of 27-242 nm and Zeta potential of -9.67 ± 0.53 mV. A total of 599 proteins were identified in the OMVs. Proteomics study indicated that the differential expressed proteins induced by OMVs with or without SAAE commonly enriched in P53 and autophagy pathways. Besides, SAAE counteracted the increased production of pro-inflammatory cytokines and attenuated the induction of cell autophagy caused by H. pylori OMVs. Furthermore, SAAE normalized the abnormal regulation of downstream targets (AIFM2 and IGFBP3) in the P53 signaling pathway caused by H. pylori OMVs. CONCLUSION: SAAE can inhibit the growth and adhesion of H. pylori, reduce the inflammation and autophagy induced by H. pylori OMVs, and combated the abnormal regulation of P53 signaling pathway caused by H. pylori OMVs. These findings may help elucidate the mechanisms through which SAAE reduces the pathogenicity of H. pylori.

Phellodendron chinense C.K.Schneid: An in vitro study on its anti-Helicobacter pylori effect.

ETHNOPHARMACOLOGICAL RELEVANCE: Phellodendron chinense C.K.Schneid(P. chinense Schneid) is known in TCM as Huang Bo, is traditionally used to support gastrointestinal function and alleviate stomach-related ailments, including gastric ulcer bleeding and symptoms of gastroesophageal reflux disease. Helicobacter pylori (H. pylori) is classified by the WHO as a Group 1 carcinogen. However, the specific activity and mechanism of action of P. chinense Schneid against H. pylori infection remain unclear. It has been noted that Huangjiu processing may alter the bitter and cold properties of P. chinense Schneid, but its effect on antimicrobial activity requires further investigation. Additionally, it remains uncertain whether berberine is the sole antimicrobial active component of P. chinense Schneid. AIM OF STUDY: This study aims to elucidate the anti-H. pylori infection activity of P. chinense Schneid, along with its mechanism of action and key antimicrobial active components. MATERIALS AND METHODS: Phytochemical analysis was carried out by UPLC-MS/MS. HPLC was employed to quantify the berberine content of the extracts. Antimicrobial activity was assessed using the micro broth dilution method. Morphology was observed using SEM. The impact on urease activity was analyzed through in vitro urease enzyme kinetics. RT-qPCR was employed to detect the expression of virulence genes, including adhesin, flagellum, urease, and cytotoxin-related genes. The adhesion effect was evaluated by immunofluorescence staining and agar culture. RESULTS: P. chinense Schneid exhibited strong antimicrobial activity against both antibiotic-sensitive and resistant H. pylori strains, with MIC ranging from 40 to 160 µg/mL. Combination with amoxicillin, metronidazole, levofloxacin, and clarithromycin did not result in antagonistic effects. P. chinense Schneid induced alterations in bacterial morphology and structure, downregulated the expression of various virulence genes, and inhibited urease enzyme activity. In co-infection systems, P. chinense Schneid significantly attenuated H. pylori adhesion and urease relative content, thereby mitigating cellular damage caused by infection. Huangjiu processing enhanced the anti-H. pylori activity of P. chinense Schneid. Besides berberine, P. chinense Schneid contained seven other components with anti-H. pylori activity, with palmatine exhibiting the strongest activity, followed by jatrorrhizine. CONCLUSIONS: This study sheds light on the potential therapeutic mechanisms of P. chinense Schneid against H. pylori infection, demonstrating its capacity to disrupt bacterial structure, inhibit urease activity, suppress virulence gene transcription, inhibit adhesion, and protect host cells. The anti-H. pylori activity of P. chinense Schneid was potentiated by Huangjiu processing, and additional components beyond berberine were identified as possessing strong anti-H. pylori activity. Notably, jatrorrhizine, a core component of P. chinense Schneid, exhibited significant anti-H. pylori activity, marking a groundbreaking discovery.