Exploring Antibacterial Potential of Anhuienoside E from Nigella sativa Linn: A Promising Candidate Against Dental Caries In Vitro and In Silico Studies

Dental caries is a chronic disease suffered by almost the entire population in the world. The main bacterium that causes dental caries is Streptococcus mutans, which has the enzyme glucosyltransferase as a virulence factor. Other fatogenic bacteria that play a role in exacerbating the biofilm form of dental caries such as Streptococccus sanguinis and Enterococcus faecalis have cell wall defenses catalyzed by the MurA enzyme. Chlorhexidine has been reported as a treatment for dental caries but has developed resistance over time. Nigella sativa L. seeds have been widely recognized to have many health benefits such as antibacterial, antioxidant and antifungal. The caries-causing antibacterial activity of N. sativa seeds has not been widely reported. The aim of this study was to isolate antibacterial compounds from N. sativa against S. mutans, S. sanguinis, E. faecalis, predict the mechanism of compounds and their derivatives by in silico molecular docking and pharmacokinetic analysis by ADMET and drug-likeness methods. Isolation of compounds was carried out by column chromatography with bioassay guidance, inhibitory mechanism and sugar substituent effects were predicted by in silico molecular docking, pharmacokinetics and drug-likeness analysis were predicted by ADMET and Lipinski rules. Anhuienoside E was successfully isolated from N. sativa extract and demonstrated antibacterial activity, which had moderate MIC and MBC values of 625 and 1000 μg/mL against S. mutans, S. sanguinis, E. faecalis. Anhuienoside E had moderate binding affinity value compared to its derivatives with ∆G values of −6.84 and −8.67 Kcal/mol against MurA and Gtf. ADMET pharmacokinetic analysis and drug-likeness evaluation suggest that Anhuienoside E and its derivatives may serve as non-toxic, non-oral drug candidates. In conclusion, Anhuienoside E has potential antibacterial activity to be developed as an alternative to chlorhexidine. The amount and type of sugar substituents greatly affect the antibacterial activity of Anhuienoside E. HIGHLIGHTS Anhuienoside E was successfully isolated from the methanol extract of sativa seeds. Anhuienoside E has antibacterial activity against mutans, S. sanguinis, E. faecalis based on MIC and MBC tests. Anhuienoside E has the potential to inhibit Gtf and MurA enzymes based on In silico molecular docking study.