Anti- Heliobacter pylori and Anti-Inflammatory Potential of Salvia officinalis Metabolites: In Vitro and In Silico Studies

Abstract

Due to its rising antibiotic resistance and associated inflammations, Helicobacter pylori poses a challenge in modern medicine. Salvia officinalis, a member of the Lamiaceae family, is a promising medicinal herb. In this regard, a phytochemical screening followed by GC-MS and LC-MS was done to evaluate the chemical profile of the total ethanolic extract (TES) and the essential oil, respectively. The anti-H. pylori and the anti-inflammatory activities were evaluated by a micro-well dilution technique and COX-2 inhibition assay. Potential anti-H. pylori inhibitors were determined by an in silico study. The results revealed that the main metabolites were flavonoids, sterols, volatile oil, saponins, and carbohydrates. The LC-MS negative ionization mode demonstrated 12 compounds, while GC-MS showed 21 compounds. Carnosic acid (37.66%), epirosmanol (20.65%), carnosol1 (3.3%), and 12-O-methyl carnosol (6.15%) were predominated, while eucalyptol (50.04%) and camphor (17.75%) were dominant in LC-MS and GC-MS, respectively. TES exhibited the strongest anti-H. pylori activity (3.9 µg/mL) asymptotic to clarithromycin (0.43 µg/mL), followed by the oil (15.63 µg/mL). Carnosic acid has the best-fitting energy to inhibit H. pylori (-46.6769 Kcal/mol). TES showed the highest reduction in Cox-2 expression approaching celecoxib with IC₅₀ = 1.7 ± 0.27 µg/mL, followed by the oil with IC₅₀ = 5.3 ± 0.62 µg/mL. Our findings suggest that S. officinalis metabolites with anti-inflammatory capabilities could be useful in H. pylori management. Further in vivo studies are required to evaluate and assess its promising activity.

Keywords: Glucose-6 phosphatase; Helicobacter pylori; Salvia officinalis; anti-inflammatory; antibacterial; essential oil; ethanolic extract.

Figure 1

[M-H] chromatogram of the S. officinal ethanolic extract.

Figure 2

Two-dimensional structures of the identified compounds of TES by LC–MS analysis (Chem-draw ultra-version 14).

Figure 2

Two-dimensional structures of the identified compounds of TES by LC–MS analysis (Chem-draw ultra-version 14).

Figure 3

GC/MS chromatogram of the essential oil of S. officinalis.

Figure 4

Two-dimensional structures of the compounds identified from the oil by GC/MS analysis (Drawn by Chem-draw ultra-version 14, PerkinElmer Informatics).

Figure 5

In vitro anti-H. Pylori activity of the total ethanol extract (TES), the essential oil of S. officinalis, and Clarithromycin.

Figure 6

Two-dimensional and three-dimensional diagrams demonstrating the interaction of the co-crystallized ligand (NADP) and identified compounds docking pose interactions with the key amino acids in the HpG6PD-binding site. The three-letter amino acid codes plus the positions of each residue are recorded. Between the receptor and the ligand, hydrogen-bonding interactions are illustrated by a green line, whereas the purple dashed line represents alkyl interactions. Two-dimensional and three-dimensional diagrams were obtained using Discovery Studio 4.5.

Figure 6

Two-dimensional and three-dimensional diagrams demonstrating the interaction of the co-crystallized ligand (NADP) and identified compounds docking pose interactions with the key amino acids in the HpG6PD-binding site. The three-letter amino acid codes plus the positions of each residue are recorded. Between the receptor and the ligand, hydrogen-bonding interactions are illustrated by a green line, whereas the purple dashed line represents alkyl interactions. Two-dimensional and three-dimensional diagrams were obtained using Discovery Studio 4.5.

Figure 6

Two-dimensional and three-dimensional diagrams demonstrating the interaction of the co-crystallized ligand (NADP) and identified compounds docking pose interactions with the key amino acids in the HpG6PD-binding site. The three-letter amino acid codes plus the positions of each residue are recorded. Between the receptor and the ligand, hydrogen-bonding interactions are illustrated by a green line, whereas the purple dashed line represents alkyl interactions. Two-dimensional and three-dimensional diagrams were obtained using Discovery Studio 4.5.

Figure 7

Anti-inflammatory activity cyclooxygenase COX-2 inhibitory % of TES and the essential oil compared to the standard drug celecoxib.