Anti -Helicobacter pylori Compounds from Oliveria decumbens Vent. through Urease Inhibitory In-vitro and In-silico Studies

Abstract

Oliveria decumbens Vent. has been used by indigenous people of southwest Iran for treating peptic ulcers and gastrointestinal infections. This study aimed to investigate the antibacterial activity of Oliveria decumbens extract and fractions and to analyze the bioactive components of the fractions. Total plant extract and different fractions of Oliveria decumbens Vent. were prepared. Antibacterial activities were evaluated against the clinical strain of Helicobacter pylori and standard strains of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa using agar dilution and disc diffusion methods. Phytochemical analysis of the fractions was performed using silica gel chromatography and 1D and 2D NMR spectroscopy. Moreover, the urease inhibitory effects of the isolated compounds were assessed in-vitro and in-silico. Three novel kaempferol derivatives and two thymol derivatives were isolated from Oliveria decumbens aerial parts, and the structures were determined by comparison with published data. The n-hexane fraction was found to exert the most significant anti-H. pylori activity with the minimum inhibitory concentration of 50 µg/mL. All fractions demonstrated antibacterial activity toward S. aureus. In-vitro urease inhibition assay showed that stigmasterol, tiliroside, and carvacrol were found to be the most potent enzyme inhibitors in the isolated compounds. Molecular interactions of the compounds with the active site of urease were supported by the molecular docking analysis. Novel bioactive compounds in Oliveria decumbens were described in this study. The antibacterial effects suggested the potential use of the compounds in pharmaceutical formulations inconsistent with the traditional use of the plant in the treatment of gastrointestinal infections.

Keywords: Anti-Helicobacter pylori; Bioactive phytochemicals; Molecular docking; Oliveria decumbens Vent; Urease inhibitory.

Figure 1

Structure of the isolated compounds from different fractions of Oliveria decumbens Vent. (a) Compound 1: Octacosane, (b)Compound 2: Carvacrol, (c) Compound 3: Thymol, (d) Compound 4: Stigmasterol, (e) Compound 5: Kaempferol-3-O-(6''-O-trans-coumaryl) glucoside (Tiliroside), (f) Compound 6: Kaempferol 3 -O-(6’’-O-trans-coumaryl)glucoside 7-O-(6’’’-O-trans-coumaryl) glucoside, (g) Compound 7: 3-Hydroxythymol-6-O-D-Glucopyranoside, (h) Compound 8: 6- Hydroxythymol-3-O-D-Glucopyranoside, (i) Compound 9: Kaempferol 3-O-neohesperidoside-7-O-[2-O-(cis-feruloyl)]-D-glucopyranoside

Figure 2

Schematic interaction of the best docking resulting from AutoDock software presented by LigPlot software for (a) Carvacrol, (b) Stigmasterol and (c) Tiliroside. In this figure, the compound exposure is highlighted in blue. Hydrogen bonding is in green and van der Waals interactions are in red circulars