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

Abstract

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.

Keywords: 1,3,6-Trigalloylglucose; Helicobacter pylori; Terminalia chebula Retz; adhesion; minimum inhibitory concentration.

Figure 1

The UPLC-MS/MS information of compound 3.

Figure 2

The structure of compound 3. CAS: 18483-17-5; CAS Name: 1,3,6-Tri-O-galloyl-β-d-glucose.

Figure 3

The scanning electron microscopy (SEM) images of the structure of HP strain ATCC 700392 after 1,3,6-Trigalloylglucose treatment for 24 h.

Figure 4

1,3,6-Trigalloylglucose inhibited the growth of HP strain ATCC 700392. (A) Urea fast test. (B) The growth curve of ATCC 700392. ** represents compared with control group, p < 0.01.

Figure 5

1,3,6-Trigalloylglucose repressed the Cag A protein. ATCC700392 was treated with different doses of 1,3,6-Trigalloylglucose (0, 16, and 32 µg/mL) for 24 h.

Figure 6

1,3,6-Trigalloylglucose acts as an anti-adhesive agent in vitro. (A) Cell viability. GES-1 cells were treated with different doses of 1,3,6-Trigalloylglucose (0–128 µg/mL) for 24 h. (B) Anti-adhesive activity. (C) NO activity. The GES-1 cells were co-cultured with HP at a ratio of 1:100, along with different doses of 1,3,6-Trigalloylglucose (0, 16, 32 µg/mL) for a duration of 6 h. ** represents compared with HP group, p < 0.01.