Computational methods to explore the therapeutic potential of Triphala, a polyherbal formulation, against LuxS protein of Helicobacter pylori

The colonization of Helicobacter pylori ( H. pylori ) in the gastric mucus can lead to various health issues, such as gastric ulcers and cancer. During colonization, H. pylori adheres to the gastric mucus thereby initiating biofilm formation and quorum sensing (QS), in which LuxS protein plays a vital role. LuxS protein functions as S-ribosylhomocysteinase that catalyzes the cleavage of S-ribosylhomocysteine into homocysteine and 4,5-dihydroxy-2,3-pentanedione (4,5-DPD). 4,5-DPD is a precursor of the autoinducer-2 (AI-2) signaling molecule. This enzymatic process contributes to the activated methyl cycle and regulates QS thereby facilitating coordinated bacterial behavior. Therefore, targeting the LuxS protein of H. pylori presents a promising approach. The present study explores the therapeutic potential of Triphala, a polyherbal formulation, against LuxS protein of H. pylori through computational methods. The diverse pharmacological effects of Triphala make it an attractive candidate for disrupting H. pylori pathogenesis. Inclusion of molecular docking, toxicity predictions and molecular dynamics simulations, this study elucidates the interactions between Triphala phytochemicals and LuxS protein. These findings revealed that specific phytochemicals from Triphala, namely furosin, corilagin, and ellagic acid exhibit superior binding affinities and bioactivity scores compared to the antibiotic clarithromycin. Molecular dynamics simulations demonstrated the stability of these complexes over time, with furosin emerging as the most stable inhibitor of LuxS protein. These results underscore Triphala and its phytochemicals as promising LuxS protein inhibitors for H. pylori treatment. The current study bridges traditional knowledge with modern computational techniques, offering insights into rational therapeutic strategies against H. pylori infection. • Computational analysis of different phytochemicals of Triphala with LuxS gene of H. pylori. • Molecular docking revealed superior binding affinity of its phytochemicals over clarithromycin. • MD simulation confirmed robust binding of its phytochemicals over clarithromycin. • Furosin emerged as the most stable LuxS inhibitor among Triphala compounds.