Phytochemical Analysis and Anti-Biofilm Potential That Cause Dental Caries from Black Cumin Seeds (Nigella sativa Linn.).

The oral cavity is an excellent place for various microorganisms to grow. Spectrococcus mutans and Spectrococcus sanguinis are Gram-negative bacteria found in the oral cavity as pioneer biofilm formers on the tooth surface that cause caries. Caries treatment has been done with antibiotics and therapeutics, but the resistance level of S. mutans and S. sanguinis bacteria necessitates the exploration of new drug compounds. Black cumin (Nigella sativa Linn.) is known to contain secondary metabolites that have antioxidant, antibacterial, anti-biofilm, anti-inflammatory and antifungal activities. The purpose of this review article is to present data on the potential of Nigella sativa Linn seeds as anti-biofilm. This article will discuss biofilm-forming bacteria, the resistance mechanism of antibiotics, the bioactivity of N. sativa extracts and seed isolates together with the Structure Activity Relationship (SAR) review of N. sativa compound isolates. We collected data from reliable references that will illustrate the potential of N. sativa seeds as anti-biofilm drug.

Stress Analysis on Mesiolingual Cavity of Endodontically Treated Molar Restored Using Bidirectional Fiber-Reinforced Composite (Wallpapering Technique).

Introduction: Endodontically treated teeth (ETT) undergo extensive structure change and experience high stress during biomechanical function. Stress distribution is influenced by the restoration material and the type of bond between material and tooth structure. The selection of materials that can distribute stress will affect the resistance and retention of ETT to mastication forces, thus biomechanical functions were achieved. Composite has mechanical properties similar to dentin, it can transmit and distribute stresses throughout the tooth surface. The disadvantage of composites in large cavities is their lack of toughness. The addition of fiber to composites can increase their toughness. Purpose: This research is to determine the stress distribution of a fiber-reinforced composite made of polyethylene and e-glass on the mesiolingual cavity of ETT. Materials and Methods: A three-dimensional model of the mandibular molar was prepared for cavity preparation and the formation of restorations using SolidWorks 2021. The models were analyzed with Abaqus 2020 to determine stress concentrations after given vertical and oblique loading. Results: The maximum and minimum principal stress data were obtained to assess material resistance and interfacial damage criterion. Polyethylene fiber shows a more homogeneous stress distribution because the modulus of elasticity is close to the dentin and has a thickness that can reduce the volume of the composite. The E-glass shows the stress concentration on the circumferential fiber and cavity floor. Conclusion: The stress distribution of fiber-reinforced composite on the buccolingual cavity of ETT using the finite element method did not show structural failure in the polyethylene group because the maximum and minimum principal stresses were lower than the strength of the material. Interfacial bond failure occurs at the enamel portion. The maximum and minimum principal values of e-glass indicate structural failure in the circumferential fiber and the base fiber because the stress exceeds the strength of the material. Interfacial bond failure occurred on the circumferential and the cavity floor.

Stress Distribution of Endodontically Treated Tooth MOD Cavity Restored with Ribbon Fiber-Reinforced Composite (Wallpapering Technique) Using Finite Element Method.

Purpose: This research aimed to describe the stress distribution of an endodontically treated tooth with a mesio-occluso-distal (MOD) cavity restored with direct composite reinforced with polyethylene and e-glass ribbon fiber. Methods: This research was a descriptive study using the finite element method. A 3D model of the mandibular first molar solid after endodontic treatment with class II MOD preparation was prepared using Solidworks software. Finite element simulation was carried out using Abaqus software. In the first simulation, 180 N force was applied (vertically 90° perpendicular to the occlusal surface) at four points of loading: the tip of the mesiobuccal and distobuccal cusp, central fossa, and distal marginal ridge. For the second simulation, a 100 N force was applied at a 45° lateral angle to the occlusal surface at two loading points: the lingual slope of the mesiobuccal and distobuccal cusp. Results: This study showed that the stress concentration was located in the occlusal pit and fissure, CEJ distal area, bifurcation in dentin, and the 1/3 cervical area of root dentin. The stress value generated after vertical and lateral force did not exceed the tooth and restoration's compressive and tensile strength value. The failure occurred at the interface of enamel and composite near the loading point area due to vertical load, both on polyethylene and e-glass fiber ribbon-reinforced composite restoration. Stress distribution of an endodontically treated tooth with a MOD cavity restored with ribbon fiber-reinforced composite using the finite element method showed that the highest stress concentration occurred on the surface close to the loading point, in narrow, concave, and sharp areas, and more apically for endodontically treated teeth. Conclusion: Neither the tooth nor restoration failed after vertical and horizontal loads. The interface between enamel and composite on the occlusal surface failed.

In silico Study of Antiviral Activity of Polyphenol Compounds from Ocimum basilicum by Molecular Docking, ADMET, and Drug-Likeness Analysis.

Aim: The SARS-CoV-2 virus is a disease that has mild to severe effects on patients, which can even lead to death. One of the enzymes that act as DNA replication is the main protease, which becomes the main target in the inhibition of the SARS-CoV-2 virus. In finding effective drugs against this virus, Ocimum basilicum is a potential herbal plant because it has been tested to have high phytochemical content and bioactivity. Apigenin-7-glucuronide, dihydrokaempferol-3-glucoside, and aesculetin are polyphenolic compounds found in Ocimum basilicum. Purpose: The purpose of this study was to analyze the mechanism of inhibition of the three polyphenolic compounds in Ocimum basilicum against the main protease and to predict pharmacokinetic activity and the drug-likeness of a compound using the Lipinski Rule of Five. Patients and Methods: The method used is to predict the molecular docking inhibition mechanism using Autodock 4.0 tools and use pkcsm and protox online web server to analyze ADMET and Drug-likeness. Results: The binding affinity for apigenin-7-glucuronide was -8.77 Kcal/mol, dihydrokaempferol-3-glucoside was -8.96 Kcal/mol, and aesculetin was -5.79 Kcal/mol. Then, the inhibition constant values were 375.81 nM, 270.09 nM, and 57.11 µM, respectively. Apigenin-7-glucuronide and dihydrokaempferol-3-glucoside bind to the main protease enzymes on the active sites of CYS145 and HIS41, while aesculetin only binds to the active sites of CYS145. On ADMET analysis, these three compounds met the predicted pharmacokinetic parameters, although there are some specific parameters that must be considered especially for aesculetin compounds. Meanwhile, on drug-likeness analysis, apigenin-7-glucuronide and dihydrokaempferol-3-glucoside compounds have one violation and aesculetin have no violation. Conclusion: Based on the data obtained, Apigenin-7-glucuronide and dihydrokaempferol-3-glucoside are compounds that have more potential to have an antiviral effect on the main protease enzyme than aesculetin. Based on pharmacokinetic parameters and drug-likeness, three compounds can be used as lead compounds for further research.

The Potential of 24-Propylcholestrol as Antibacterial Oral Bacteria of Enterococcus faecalis ATCC 29212 and Inhibitor Biofilms Formation: in vitro and in silico Study.

Introduction: Uncontrolled biofilm can cause several diseases such as dental caries, gingivitis, and periodontitis. Dental caries is a disease caused by the accumulation of plaque-containing pathogenic bacteria, including Enterococcus faecalis. These bacteria infect the root canals of teeth and colonize to form biofilms. Biofilm inhibition is carried out by interfering with cell wall formation metabolism. MurA enzyme has a role in peptidoglycan biosynthesis of cell walls. Enterococcal surface protein (Esp) is the main contributor of E. faecalis to form biofilms. In addition, inhibition of biofilms by interfering with the quorum sensing (QS) system, suppressing gelatinase virulence factors by blocking autoinducers gelatinase biosynthesis-activating pheromone (GBAP). Purpose: Knowing the potential of Piper betel Linn. compounds as antibacterial in vitro and antibiofilm agents against E. faecalis in silico. Patients and Methods: The compounds were purified by a bioactivity-guided chromatographic method. Antibacterial activity was tested by disc diffusion method, in vitro studies. In silico study, compound P. betel L. was used as the test ligand and compared with positive control fosfomycin, ambuic acid, quercetin, and taxifolin. The proteins used MurA, Esp, GBAP, and gelatinase were docking with the Autodock Vina PyRx 0.8 followed by the PYMOL program and visualized with the Discovery Studio 2020 program. Results: An antibacterial compound was identified 24-propylcholesterol which can inhibit the activity of E. faecalis ATCC 29212 with MIC value of 78.1 µg/mL and MBC value of 156.3 µg/mL. Molecular docking results showed the binding affinity of 24-propylcholesterol with MurA, ESP, GBAP, and gelatinase enzymes was -7.6, -8.7, -5.3, and -7.9 kcal/mol. Conclusion: 24-propylcholesterol has potential as an antibacterial against E. faecalis and as an antibiofilm through in silico inhibition of QS. However, further research is needed in vitro and in vivo to determine the effectiveness of these compounds as antibacterial and antibiofilm.

Ocimum Species: A Review on Chemical Constituents and Antibacterial Activity.

Infection by bacteria is one of the main problems in health. The use of commercial antibiotics is still one of the treatments to overcome these problems. However, high levels of consumption lead to antibiotic resistance. Several types of antibiotics have been reported to experience resistance. One solution that can be given is the use of natural antibacterial products. There have been many studies reporting the potential antibacterial activity of the Ocimum plant. Ocimum is known to be one of the medicinal plants that have been used traditionally by local people. This plant contains components of secondary metabolites such as phenolics, flavonoids, steroids, terpenoids, and alkaloids. Therefore, in this paper, we will discuss five types of Ocimum species, namely O. americanum, O. basilicum, O. gratissimum, O. campechianum, and O. sanctum. The five species are known to contain many chemical constituents and have good antibacterial activity against several pathogenic bacteria.

Mode action prediction of catechin from Uncaria gambir Roxb. against UDP-N-acetylenolpyruvyl-glucosamine reductase (MurB enzyme) of Streptococcus mutans: In silico study.

The prevalence of oral health problems in the global population is still high, especially dental caries, which is considered a multifactorial disease involving the role of bacteria, namely Streptococcus mutans. Gram-positive bacteria metabolize carbohydrates and sugars and convert them into lactic acid, causing dental caries. The peptidoglycan (PG) layer at the outer surface of the bacteria acts as protection. MurB enzyme is known for its contribution to PG biosynthesis. Gambir (Uncaria gambir Roxb.) is famous for many efficacies. Previous studies show that catechin from herb plants such as U. gambir has antibacterial activity. This study aimed to evaluate and predict the antibacterial activity of catechin from U. gambir against the MurB enzyme, which contributes to forming the bacteria PG, with an in silico approach. The structure of the MurB enzyme was collected from UniProt, and the ligands (catechin and chlorhexidine) structures were obtained from PubChem. The AutoDock software was used to dock both ligand and MurB enzyme visualized using PyMOL and analyzed using BIOVIA. The results showed that catechin has a binding affinity of more than - 7 kcal/mol against the MurB enzyme, and chlorhexidine has a higher binding affinity than catechin. Both catechin and chlorhexidine have similar amino acids attachment by hydrogen bonds. The results showed that catechin has competitive antibacterial activity against chlorhexidine in inhibiting the MurB enzyme.

Bio-Mechanism of Catechin as Pheromone Signal Inhibitor: Prediction of Antibacterial Agent Action Mode by In Vitro and In Silico Study.

The utilization of medicinal plants has long been explored for the discovery of antibacterial agents and the most effective mechanisms or new targets that can prevent and control the spread of antibiotic resistance. One kind of bacterial cell wall inhibition is the inactivation of the MurA enzyme that contributes to the formation of peptidoglycan. Another approach is to interfere with the cell-cell communication of bacteria called the Quorum sensing (QS) system. The blocking of auto-inducer such as gelatinase biosynthesis-activating pheromone (GBAP) can also suppress the virulence factors of gelatinase and serine protease. This research, in particular, aims to analyze lead compounds as antibacterial and anti-QS agents from Gambir (Uncaria gambir Roxburgh) through protein inhibition by in silico study. Antibacterial agents were isolated by bioactivity-guided isolation using a combination of chromatographic methods, and their chemical structures were determined by spectroscopic analysis methods. The in vitro antibacterial activity was evaluated by disc diffusion methods to determine inhibitory values. Meanwhile, in the in silico analysis, the compound of Uncaria gambir was used as ligand and compared with fosfomycin, ambuic acid, quercetin, and taxifolin as the standard ligand. These ligands were attached to MurA, GBAP, gelatinase, and serine proteases using Autodock Vina in PyRx 0.8 followed by PYMOL for combining the ligand conformation and proteins. plus programs to explore the complex, and visualized by Discovery Studio 2020 Client program. The antibacterial agent was identified as catechin that showed inhibitory activity against Enterococcus faecalis ATCC 29212 with inhibition zones of 11.70 mm at 10%, together with MIC and MBC values of 0.63 and 1.25 µg/mL, respectively. In the in silico study, the molecular interaction of catechin with MurA, GBAP, and gelatinase proteins showed good binding energy compared with two positive controls, namely fosfomycin and ambuic acid. It is better to use catechin-MurA (-8.5 Kcal/mol) and catechin-gelatinase (-7.8 Kcal/mol), as they have binding energies which are not marginally different from quercetin and taxifolin. On the other hand, the binding energy of serine protease is lower than quercetin, taxifolin, and ambuic acid. Based on the data, catechin has potency as an antibacterial through the inhibition of GBAP proteins, gelatinase, and serine protease that play a role in the QS system. This is the first discovery of the potential of catechin as an alternative antibacterial agent with an effective mechanism to prevent and control oral disease affected by antibiotic resistance.

Action mode of ursolic acid as a natural antioxidant and inhibitor of superoxide dismutase: In vitro and in silico study.

Recently, the antioxidant is applied for the teeth bleaching treatment as an alternative of toxic material of hydrogen peroxide that is used in teeth bleaching. One of natural sources antioxidant is Uncaria gambir those containing active antioxidant agents. To be applied as a new bioactive constituent in teeth bleaching treatment, a preexperimental study is performed. The aim of the study is to identify the antioxidant constituent of U. gambir and predict their activity including action mode as an inhibitor of enzyme superoxide dismutase (SOD) through in vitro and in silico method. Combination of chromatography methods and spectroscopic analysis is used for isolated bioactive antioxidant constituent. The antioxidant activity was evaluated by in vitro assay against diphenylpicrylhydrazyl (DPPH)and SOD, respectively, while prediction of action mode of the active compounds as SOD-mutant enzyme inhibitor was conducted by in silico study using AutoDock 4.2 program. Antioxidant of ursolic acid was isolated from U. gambir with inhibitory concentration50 values 1721 ± 30.6 and 392 ± 53.57 µg/mL, respectively, against DPPH and SOD. By in silico study presented that ursolic acid inhibited SOD enzyme with a binding affinity of - 5.4 kcal/mol those higher than a quercetin as a positive control. The ursolic acid was identified as a potential natural antioxidant with potentially activity to inhibit SOD mutant.

Effectiveness of Bioactive Compound as Antibacterial and Anti-Quorum Sensing Agent from Myrmecodia pendans: An In Silico Study.

BACKGROUND: antibiotic resistance encourages the development of new therapies, or the discovery of novel antibacterial agents. Previous research revealed that Myrmecodia pendans (Sarang Semut) contain potential antibacterial agents. However, specific proteins inhibited by them have not yet been identified as either proteins targeted by antibiotics or proteins that have a role in the quorum-sensing system. This study aims to investigate and predict the action mode of antibacterial compounds with specific proteins by following the molecular docking approach. METHODS: butein (1), biflavonoid (2), 3″-methoxyepicatechin-3-O-epicatechin (3), 2-dodecyl-4-hydroxylbenzaldehyde (4), 2-dodecyl-4-hydroxylbenzaldehyde (5), pomolic acid (6), betulin (7), and sitosterol-(6'-O-tridecanoil)-3-O-ß-D-glucopyranoside (8) from M. pendans act as the ligand. Antibiotics or substrates in each protein were used as a positive control. To screen the bioactivity of compounds, ligands were analyzed by Prediction of Activity Spectra for Substances (PASS) program. They were docked with 12 proteins by AutoDock Vina in the PyRx 0.8 software application. Those proteins are penicillin-binding protein (PBP), MurB, Sortase A (SrtA), deoxyribonucleic acid (DNA) gyrase, ribonucleic acid (RNA) polymerase, ribosomal protein, Cytolysin M (ClyM), FsrB, gelatinase binding-activating pheromone (GBAP), and PgrX retrieved from UniProt. The docking results were analyzed by the ProteinsPlus and Discovery Studio software applications. RESULTS: most compounds have Pa value over 0.5 against proteins in the cell wall. In nearly all proteins, biflavonoid (2) has the strongest binding affinity. However, compound 2 binds only three residues, so that 2 is the non-competitive inhibitor. CONCLUSION: compound 2 can be a lead compound for an antibacterial agent in each pathway.