A terpenoid isolated from sarang semut (Myrmecodia pendans) bulb and its potential for the inhibition and eradication of Streptococcus mutans biofilm.

BACKGROUND: Dental caries remains a serious problem due to its detrimental effects on individual health and quality of life. The bulbs of Myrmecodia pendans (Merr & Perry), native plants of Papua, have been used as natural remedies for tumours, gout, diarrhoea, and fever. In this study, one of the active compounds of M. pendans was isolated, and its biological activity against the formation of Streptococcus mutans ATCC 25175 biofilm was tested. METHODS: M. pendans was extracted with ethyl acetate using a Soxhlet apparatus. The extract was then separated, and chromatographic purification provided the isolated compound. The structure of the active compound was then characterized using UV, IR, NMR, and MS spectrometry. The obtained compound was added to S. mutans biofilms to determine the MBIC and MBEC values. RESULTS: The compound isolated from M. pendans was determined to be a labdane diterpene derivative with the formula C31H50O3. The MBIC value of the terpenoid towards the S. mutans biofilms was 50 ppm, and the MBEC value for the 1 min induction time was 40%. CONCLUSION: The terpenoid extracted from M. pendans has the potential to be developed into an antibacterial agent particularly for preventing the formation of biofilms.

Potential of MurA Enzyme and GBAP in Fsr Quorum Sensing System as Antibacterial Drugs Target: In vitro and In silico Study of Antibacterial Compounds from Myrmecodia pendans.

BACKGROUND: Increasing the resistance issue has become the reason for the development of new antibacterial in crucial condition. Many ways are tracked to determine the most effective antibacterial agent. Some proteins that are a key role in bacteria metabolism are targeted, including MurA in cell wall biosynthesis and gelatinase biosynthesis-activating pheromone (GBAP) in Fsr Quorum Sensing (QS) system. OBJECTIVE: The objective of this research is the analysis of compounds 1-4 from M. pendans as antibacterial and anti-QS activity trough protein inhibition by in silico study; focus on the structure-activity relationships, to appraise their role as an antibacterial and anti-QS agent in the molecular level. METHODS: Both activities of M. pendans compounds (1-4) were analyzed by in silico, compared to Fosfomycin, Ambuic acid, Quercetin, and Taxifolin as a standard. Chemical structures of M. pendans compounds were converted using an online program molview. The compounds were docked to MurA, GBAP, gelatinase and serine protease using Autodock Vina in Pyrx 0.8 followed PYMOL to visualization and proteis.plus program to analyze of the complex. RESULTS: All compounds from M. pendans bound on MurA, GBAP, gelatinase and serine protease except compound 2. This biflavonoid did not attach to MurA and serine protease yet is the favorable ligand for GBAP and gelatinase with the binding affinity of -6.9 and -9.4 Kcal/mol respectively. Meanwhile, for MurA and serine protease, compound 4 is the highest of bonding energy with values of -8.7 and -6.4 Kcal/mol before quercetin (MurA, -8.9 Kcal/mol) and taxifolin (serine protease, -6.6 Kcal/mol). CONCLUSION: Based on the data, biflavonoid acts better as anti-QS than an inhibitor of MurA enzyme while the others can be acted into both of them either the therapeutic agent of anti-QS or antibacterial agent of MurA inhibitor.

Antibacterial of Dibenzo-p-Dioxi-2,8-Dicarboxylic Acid Against Pathogenic Oral Bacteria E. faecalis ATCC 29212 Peptide Pheromones: Quorum Sensing of in vitro and in silico Study.

BACKGROUND: Recently, it has emerged from the international scientific literature that quorum sensing (QS) is a promising way for the effective treatment of diseases caused by pathogenic bacteria. One of the crucial proteins in the QS system of Gram-positive bacteria is the pheromone. Some research has reported secondary metabolites from natural products capable of attenuating bacteria through the interruption of the quorum sensing system. One of the Indonesian herbal plants containing bioactive compounds is Sarang Semut (Myrmecodia pendans). A phenolic compound, dibenzo-p-dioxin-2,8-dicarboxylic acid, has been isolated from this plant which had antibacterial activity against Enterococcus faecalis. However, the molecular mechanism of it has not been known. AIM: The study in question aimed to predict the molecular action of the compound M. pendans against some proteins that act as a signal in the mediated QS of Gram-positive bacteria, called pheromones, including PrgQ, PrgX, PrgZ, and CcfA. MATERIALS AND METHODS: The methods used in this in silico study were ligand-protein docking and virtual screening that were performed by some software and programs. The compound 1 and some positive controls act as ligand were subject binding to PrgQ, PrgX, PrgZ, and CcfA as proteins target, the ligands were free for blind docking. A framework was presented potency of phenolic compounds to inhibit the protein's target from its affinity binding scores. RESULTS: It was found thatcompound 1 was potential to inhibit all of the tested protein and gave the highest binding affinity to PrgX (-9.2 kcal.mol-1; the site at Phe59B, Phe59B, Asn63A, and Asn63B residue) and PrgZ (-7.4 kcal.mol-1; the site at Leu4B, Thr65A, Thr82A. Gln81A, and Val5B residue). CONCLUSION: It is proposed that compound 1 has a good activity to inhibit E. faecalis through its peptide pheromones in the QS system.

Antibacterial Flavonoids Against Oral Bacteria of Enterococcus Faecalis ATCC 29212 from Sarang Semut (Myrmecodia pendans) and Its Inhibitor Activity Against Enzyme MurA.

BACKGROUND: A significant number of antibiotics are known to inhibit peptidoglycan synthesis in the cross-linking stage, while the drug fosfomycin is the only one known to inhibit MurA. Escalated antibiotic resistance has had an impact on the efficacy of fosfomycin, thus demanding the discovery of suitable substitutes with improved potential for MurA inhibition. The aim of this work is to isolate antibacterial compounds from Sarang Semut (Myrmecodia pendans) and to evaluate their antibacterial activity against pathogenic oral bacteria of Enterococcus faecalis ATCC 29212 and inhibitory activity against MurA enzyme. METHODS: The antibacterial compounds from Sarang Semut were isolated by a bioactivity-guided separation method with various solvents and combination of column chromatography on normal and reverse phases. The compounds with concentrations of 1000 and 5000 ppm were assessed against E. faecalis ATCC 29212 by agar well diffusion method, with chlorhexidine and fosfomycin being used as positive controls. RESULTS: Two antibacterial compounds isolated from Sarang Semut were identified as two new flavonoids derivates of 1 (10 mg) and 2 (4 mg). Both compounds were tested for antibacterial activities against E. faecalis. MIC values of compounds 1 and 2 were 8.15 and 8.05 mm at 1000 ppm and 8.62 and 8.55 mm at 5000 ppm, respectively. MBC values were 156 and 625 ppm for 1 and 625 and 2500 ppm for 2, respectively. In an inhibitory murA enzyme activity assay, compounds 1 and 2 were shown to inhibit the enzyme activity by IC50 values of 21.7 and 151.3 ppm. CONCLUSION: The study demonstrated that ethyl acetate fraction of Sarang Semut contained antibacterial flavonoids as active constituents that showed activity against E. faecalis. These results showed the plant's potential in herbal medicine and the development of new antibacterial agent for pathogenic dental caries.

Difference of concentration of placental soluble fms-like tyrosine kinase-1(sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in severe preeclampsia and normal pregnancy.

BACKGROUND: Placental soluble fms-like tyrosine kinase-1 (sFlt-1) which is an antagonist of vascular endothelial growth factor and placental growth factor (PIGF), is considered as one of etiology factors cause endothelial damage in preeclampsia due to increase of sFlt-1 level that change vascular endothelial integrity. This study aims to analyze the difference of sFlt-1 and PlGF concentration in severe preeclampsia and normal pregnancy, and the correlation between both in occurrence of severe preeclampsia. METHOD: This is case control study involving 18 subjects with severe preeclampsia and 19 subjects with normal pregnancy as controls who met inclusion and exclusion criteria. Concentration of sFlt-1 and PlGF are measured with ELISA. Statistical analysis is performed with Chi square test, Fisher's exact test, T test, Mann-Whitney test, and Spearman's rank correlation test. RESULTS: This study results in no significant difference in characteristics of gestational age, and parity in both study groups. Median concentration of sFlt-1 in severe preeclampsia is higher (20,524.75 pg/mL) compared with normal pregnancy (6820.4 pg/mL). Concentration of PlGF is lower in severe preeclampsia (47 pg/mL) compared with normal pregnancy (337 pg/mL). sFlt-1 concentration is higher in severe preeclampsia compared to normal pregnancy. PlGF concentration is lower in severe preeclampsia compared to normal pregnancy. Ratio of sFlt-1 and PlGF concentration is significantly correlated in both severe preeclampsia and normal pregnancy. CONCLUSIONS: There is a significant negative correlation between the concentration of sFLt-1 and PlGF in normal pregnancy.