Harnessing plant-derived bioactive compounds as LOX-1 inhibitors in Helicobacter pylori-driven gastric inflammation

Abstract

Helicobacter pylori persistence and rising antibiotic resistance have intensified interest in host-directed adjunctive strategies. Recent studies identify LOX-1 as a gastric epithelial receptor for H. pylori catalase and support its role in bacterial adhesion, making it a plausible host-directed target. In the current study, BI-0115, a structurally defined selective LOX-1 inhibitor, was used for functional validation in gastric epithelial cells infected with two clinical H. pylori isolates. Since LOX-1 is linked to inflammatory signalling pathways, we investigated the phosphorylation of p38-MAPK, ERK1/2, JNK, and NF-?B. BI-0115 treatments reduced LOX-1-associated inflammatory cascades by inhibiting LOX-1, phosphorylated p38-MAPK, ERK 1/2, JNK, and NF-?B, while elevating E-cadherin and ZO-1 expression. Also, bioactive compounds from selected medicinal plants with known anti-oxidant, anti-inflammatory and gastroprotective properties were computationally screened against LOX-1. Docking and molecular dynamics matrix prioritized epigallocatechin (MO-24) and alpha-copaene (PN-230), comparable to the reference molecule (BI-0115). Collectively, these findings suggest LOX-1 as a plausible therapeutic target for ligand discovery in mitigating H. pylori induced pathology. � 2026 Elsevier Inc.