To determine the antibacterial effect of propolis nanoparticles (PNs) as an endodontic irrigant against Enterococcus faecalis biofilm inside the endodontic root canal system. Two-hundred-ten extracted human teeth were sectioned to obtain 6 mm of the middle third of the root. The root canal was enlarged to an internal diameter of 0.9 mm. The specimens were inoculated with E. faecalis for 21 days. Following this, specimens were randomly divided into seven groups, with 30 dentinal blocks in each group including: group I—saline; group II—propolis 100 µg/mL; group III—propolis 300 µg/mL; group IV—propolis nanoparticle 100 µg/mL; group V—propolis nanoparticle 300µg/mL; group VI—6% sodium hypochlorite; group VII—2% chlorhexidine. Dentin shavings were collected at 200 and 400 μm depths, and total numbers of CFUs were determined at the end of one, five, and ten minutes. The non-parametric Kruskal–Wallis and Mann–Whitney tests were used to compare the differences in reduction in CFUs between all groups, and probability values of p < 0.05 were set as the reference for statistically significant results. The antibacterial effect of PNs as an endodontic irrigant was also assessed against E. faecalis isolates from patients with failed root canal treatment. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were also performed after exposure to PNs. A Raman spectroscope, equipped with a Leica microscope and lenses with curve-fitting Raman software, was used for analysis. The molecular interactions between bioactive compounds of propolis (Pinocembrin, Kaempferol, and Quercetin) and the proteins Sortase A and β-galactosidase were also understood by computational molecular docking studies. PN300 was significantly more effective in reducing CFUs compared to all other groups (p < 0.05) except 6% NaOCl and 2% CHX (p > 0.05) at all time intervals and both depths. At five minutes, 6% NaOCl and 2% CHX were the most effective in reducing CFUs (p < 0.05). However, no significant difference was found between PN300, 6% NaOCl, and 2% CHX at 10 min (p > 0.05). SEM images also showed the maximum reduction in E. faecalis with PN300, 6% NaOCl, and 2% CHX at five and ten minutes. CLSM images showed the number of dead cells in dentin were highest with PN300 compared to PN100 and saline. There was a reduction in the 484 cm⁻¹ band and an increase in the 870 cm⁻¹ band in the PN300 group. The detailed observations of the docking poses of bioactive compounds and their interactions with key residues of the binding site in all the three docking protocols revealed that the interactions were consistent with reasonable docking and IFD docking scores. PN300 was equally as effective as 6% NaOCl and 2% CHX in reducing the E. faecalis biofilms.

This systematic review aims to evaluate the antimicrobial activity of α-mangostin derived from Garcinia mangostana against different microbes. A literature search was performed using PubMed and Science Direct until March 2022. The research question was developed based on a PICO (Population, Intervention, Control and Outcomes) model. In this study, the population of interest was microbes, α-mangostin extracted from Garcinia mangostana was used as exposure while antibiotics were used as control, followed by the outcome which is determined by the antimicrobial activity of α-mangostin against studied microbes. Two reviewers independently performed the comprehensive literature search following the predetermined inclusion and exclusion criteria. A methodological quality assessment was carried out using a scoring protocol and the risk of bias in the studies was analyzed. Reward screening was performed among the selected articles to perform a meta-analysis based on the pre-determined criteria. Case groups where α-mangostin extracted from Garcinia mangostana was incorporated were compared to groups using different antibiotics or antiseptic agents (control) to evaluate their effectiveness. A total of 30 studies were included; they were heterogeneous in their study design and the risk of bias was moderate. The results showed a reduction in microbial counts after the incorporation of α-mangostin, which resulted in better disinfection and effectiveness against multiple microbes. Additionally, the meta-analysis result revealed no significant difference (p > 0.05) in their effectiveness when α-mangostin was compared to commercially available antibiotics. α-mangostin worked effectively against the tested microbes and was shown to have inhibitory effects on microbes with antibiotic resistance.

Aim: To formulate and characterize a palm-oil-in-water-based α-Mangostin nano-emulsion (PO-AMNE) endodontic irrigant, in order to evaluate its antibacterial efficacy against Enterococcus faecalis, Staphylococcus epidermidis, and Candida albicans biofilms, as well as its capacity to remove smear layer. Methods: The solubility of α-Mangostin in various oils was determined and selected, surfactants and co-surfactants were used for the nano-emulsion trial. PO-AMNE was prepared and optimized. The MIC was performed, and the antimicrobial efficacy was estimated against biofilms. The optimized 0.2% PO-AMNE irrigant antimicrobial efficacy in a tooth model was done using colony-forming units. The treated teeth were processed by scanning electron microscopic examination for debris and smear layer removal. An Alamar Blue assay was used to evaluate cell viability. The optimization of the PO-AMNE irrigant was performed using Box–Behnken statistical design. Results: The optimized 0.2% PO-AMNE irrigant was found to have a particle size of 340.9 nm with 0.246 PDI of the dispersed droplets, and a zeta potential (mV) of −27.2 ± 0.7 mV. The MIC values showed that 0.2% PO-AMNE (1.22 ± 0.02) were comparable to 2% CHX (1.33 ± 0.01), and 3.25% NaOCl (2.2 ± 0.09) had the least inhibition for E. faecalis. NaOCl (3.25%) showed the maximum inhibition of S. epidermidis (0.26 ± 0.05), whereas 0.2% PO-AMNE (1.25 ± 0.0) was comparable to 2% CHX (1.86 ± 0.07). For C. albicans, 2% CHX (8.12 ± 0.12) showed the least inhibition as compared to 0.2% PO-AMNE (1.23 ± 0.02) and 3.25% NaOCl (0.59 ± 0.02). The 0.2% PO-AMNE irrigant was then evaluated for its antimicrobial efficacy against the three biofilms, using colony-forming units. The 0.2% PO-AMNE was comparable to both 3.25% NaOCl and 2% CHX in inhibiting the growth of biofilms. The 0.2% PO-AMNE and 17% EDTA eliminated the smear layer with the lowest mean scores (p < 0.001). Finally, 0.2% PO-AMNE was shown to be biocompatible when compared to 17% EDTA, 3.25% NaOCl, and 2% CHX in immortalized oral keratinocyte cells. Conclusion: Overall, the formulated 0.2% PO-AMNE irrigant was an effective antimicrobial and biocompatible which could combat endodontic-infection-related polymicrobial biofilms.