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Scientific herbal formulations are used clinically to treat hypertension, but their functional molecular mechanisms remain unclear. This study identified the molecular pathways of scientific herbal remedies in treating hypertension work. The identified compounds were then excluded by measuring oral bioavailability and drug similarity. The network was created using Cytoscape version 3.8, and the predicted target information was obtained from a number of databases, such as SwissTarget Prediction, STRING, Online Mendelian Inheritance in Man, and Kyoto Encyclopedia of Genes and Genomes (KEGG). The decoction's method for lowering hypertension was then clarified using an enrichment analysis. It was discovered that bioavailability and drug similarity metrics existed for 44 identified substances. The results of pathway analysis using KEGG revealed that the potential targets were correlated with the antihypertensive mechanism of herbal medicine such as the HIF-1, relaxin, PI3K, and MAPK signaling pathway. Scientific herbal formulas' pressure-lowering mechanisms include those related to vascular endothelium and atherosclerosis, which involve several signaling pathways such as HIF-1, relaxin, PI3K, and MAPK. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this research was to evaluate and select the best architecture among native convolutional neural network (CNN), MobileNetV2, ResNet50V2, and EfficientNetB0 for predicting the endpoint of the high shear wet granulation process, with accuracy as the main evaluation metric. Methods: The dataset was captured from an industrial camera using static image analysis and was manually labeled as “NOT READY” and “READY” according to the traditional endpoint method based on the mixer’s ampere point in the granulator. The dataset contained a total of 180 images, which were split between training and validation sets. Native CNN and TensorFlow Keras application programming interface (API) were utilized with MobileNetV2, EfficientNetB0, and ResNet50V2 as base feature encoders. Hyperparameters, such as final Fully Connected (FC) layer width, dropout rate, and learning rate, were optimized for binary classification using Keras hyper tuning. Results: The best was the native CNN, it was also the fastest among the three other models, taking only 20-30 ms per step for inference during runtime, though it requires 9000 ms time for training, the longest time among the models. It achieved an accuracy of 98%, and a validation accuracy of 97%. Conclusion: The system was able to determine when a wet granulation process has reached its endpoint based on live images from a camera after being trained on previously labeled data. The native CNN was the best model, offering the fastest runtime performance and the highest accuracy. [ABSTRACT FROM AUTHOR]

Pluchea indica (L.) Less is traditionally utilized to treat postpartum women in Indonesia. The plant has many pharmacological properties, so that it can be further developed as herbal medicine. In that development process, plant authentication is needed to ensure the quality of raw materials. A simple microscopical and thin-layer chromatography (TLC) analysis might be a way to authenticate the plant, but it has never been reported. So, this study evaluates the microscopical and TLC analysis for P. indica authentication in standardized herbal medicines production. Plant microscopic observation, fluorescence analysis, and polyphenol screening were conducted. n-Hexane, ethyl acetate, and methanol extracts of plant organs were then analyzed by TLC. Here, we reported that in microscopical analysis the simplicia of P. indica contains trichomes and tannin-containing cells. In addition, chlorogenic acid as a marker was present in TLC analysis by ethyl acetate-water-formic acid-acetic acid (8.5:1.5:1:1, v/v). The results of this evaluation might provide additional information in the identification, authentication, and quality control of P. indica as a raw material for herbal medicine. [ABSTRACT FROM AUTHOR]

The SIRT1 is overexpressed in a number of cancers. As a result, inhibiting SIRT1 may be used as a cancer treatment technique. Modification of 1-benzoyl-3-methylthiourea derivatives was carried out in this study by changing the aromatic side. The designed compounds (94) were subjected to in silico docking, pharmacokinetics, and preclinical testing. In the docking sample, the (4-decyl-N-(methylcarbamothioyl)benzamide (91), 2-(benzyloxy)-N-(methylcarbamo-thioyl)benzamide (93) and N-(methylcarbamothioyl)-2-naphthamide (94) were predicted to display better inhibition of SIRT1, so they were chosen for subsequent molecular dynamic studies. The compound 93 is proposed as a possible anticancer candidate that inhibits SIRT1 based on the screening results from molecular docking, pharmacokinetic predictions, and molecular dynamics. [ABSTRACT FROM AUTHOR]

In Indonesia, the number of cases infected with Covid-19 peaked between mid-June and August 2021, resulting in the denial of hospital treatment to some people due to insufficient capacity. Therefore, people treat themselves by using natural ingredients. This study aims to identify plants that can treat Covid-19 with self-medication. This study took a description approach to investigate people using traditional herbs in self-medication for COVID-19 recovery. Snowball sampling is the approach used. Interviews and an online system (gform) were used to collect data. The number of samples collected allows for a more thorough analysis of the 104 respondents. The results showed that women (51.0%), people aged between 56 and 65 (52.9%), Banten residents (32.7%), secondary education (57. 7%), and people with comorbidities (86.5). %) were all interested in using traditional herbal medicine. Reduction of symptoms and results of laboratory tests were used to measure recovery. The most common comorbidities were hypertension (7-14 days to recovery), diabetes mellitus (15-21 days to recovery), and cardiovascular disease (7-14 days and 15-21 days to recovery). The Zingiberaceae family dominates traditional herbs. The most widely used traditional ingredients are Empon-Empon, which consists of red ginger, turmeric, nutmeg, aromatic ginger, bay leaves, lemongrass, galangal, cinnamon, and cloves. The average healing time is 7-14 days (32.7%). In conclusion people who utilized herbal medicines reported a speedy recovery and reduction in the severity of their symptoms. [ABSTRACT FROM AUTHOR]

The Janus tyrosine kinases (JAKs) have shown great promise as therapeutic protein targets in the treatment of cancer and inflammation diseases. This study used pharmacophore modeling to identify potential inhibitors of Janus kinase 3 (JAK3). A pharmacophore model was developed based on a known JAK3 inhibitor (1NX) and was employed to search for potential JAK3 inhibitors against Indonesian herbal compounds. Among 28 hit molecules that were identified and subjected to a molecular docking protocol against JAK3, the three compounds that had the highest affinities toward JAK3 were camelliaside B, 3- O-galloylepicatechin-(4beta-6)-epicatechin-3-O-gallate, and mesuaferrone B. These were then each subjected to a 50-ns molecular dynamics (MD) simulation. Analysis of RMSD and RMSF values indicated that the three compounds reached stability during the MD simulation. Interestingly, all three compounds had lower binding energies than 1NX against JAK3, as predicted by the MMPBSA binding energy calculation. [ABSTRACT FROM AUTHOR]

Andrographolide is the marker compound of Andrographis paniculata (Kalmegh), a herb that constitutes many traditional Asian remedies. In the present photochemical approach to modify its 12-en-14-hydroxyl moiety into 13-enone, a methanol solution of andrographolide has been illuminated with blue laser for 6 hours in the presence of sodium bicarbonate. After the illumination, it has been discovered that the 12-en-14-hydroxyl moiety undergoes modification into the 11-enone. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase-IV (DPP-IV) inhibitor is one of the drug targets for the treatment of diabetes. Some classes of those drugs have dangerous side effects so is critical to develop safer drugs. By using rotation forest methods and in silico, it will be more efficient than conventional methods that require a lot more costs and are more time-consuming. One of in silico methods used in drug design is ligand-based virtual screening (LBVS). The interlocking structure capabilities are identified by the LBVS Process. The fingerprint is one of the structural interpretations. Molecular fingerprints are used as a criterion for LBVS in computational drug discovery. A circular fingerprint is found to improve LBVS performance. In this paper, we used the representation of ECFP and FCFP as a method to extract features, after which we used a Rotation Forest classifier to predict active and inactive compounds. The experiment result shows Rotation Forest has good prediction based on the different circular fingerprint and can successfully better classify with results of MCC being 85% and accuracy 92%. [ABSTRACT FROM AUTHOR]

Several of the DPP-4 inhibitors in the treatment of type 2 diabetes (T2DM) still have unsafe side effects in long-term use. It is necessary to develop a new DPP-4 inhibitor to minimize these unsafe side effects of the drug. QSAR is a model that can be used for the development of DPP-4 inhibitor drugs. The selection of a subset of DPP-4 inhibitor molecules by applying the clustering method can be made to improve the accuracy of the QSAR model. This study aims to select the corresponding DPP-4 inhibitor molecules by using the MiniBatchKMeans algorithm with Levenshtein distance and based on the log P criteria of 'Lipinski's Rule of 5' for QSAR modeling. The research began with the collection of DPP-4 inhibitor molecule data from the ChEMBL database site (https://www.ebi.ac.uk/chembl/) in CSV format. A representation of the molecular structure of the data is obtained from their SMILES features. Before running the clustering process, data in the form of SMILES is extracted into molecular fingerprints using several fingerprint generators, namely MACCS, ECFP, and FCFP. Clustering was carried out on five fingerprint datasets, including ECFP (with 4 and 6 diameters), FCFP (with 4 and 6 diameters), and MACCS (167 structural keys). The clustering process begins by determining the optimal number of clusters evaluated by applying the Davies-Bouldin index, the Silhouette coefficient, and the Calinski Harabasz score. Based on the clustering process, 1540 clusters were obtained from the minimum DBI cluster evaluation values of 0.545311, maximum SCO of 0.302842, and maximum CHS of 331.3942 from the MACCS fingerprint dataset. Based on log P criteria from 'Lipinski's Rule of 5', 1532 molecules were obtained for the molecular selection process that have log P values between -0.205 to 4.95. [ABSTRACT FROM AUTHOR]

Background: HIV continues to be a major global public health issue, having claimed more than 35 million lives so far. In 2016, 1 million people died from HIV-related causes globally. HIV-1 reverse transcriptase is one of HIV's vital enzymes for virus reproduction. If the enzyme is inhibited, the virus multiplication could be significantly decreased. There are currently many treatments for HIV, but more effective treatment is always needed because of the possibility of drug resistance and side effects for long-term use. Based on the previous study, there are some natural compounds with high affinity to the HIV-1 reverse transcriptase enzyme. Some of these compounds are flavonoid glycosides. Aims and Method: This study was aimed to learn more about in silico HIV-1 reverse transcriptase inhibitory activities of flavonoid glycosides using docking method. Results: The results showed that the most recommended flavonoid glycosides are those with the lowest binding energy, which were kaempferol-3-O-rhamnoside, myricetin-3-O-rhamnoside and quercetin-3-O-rhamnoside. This was due to the interactions of all three flavonoid rings and sugar moiety with key amino acid residues, which were Leu100, Lys101, Glu138, Tyr181, His235 and Tyr318. Conclusion: Flavonoid glycosides with rhamnose as glycone showed lower binding energy on HIV-1 reverse transcriptase. [ABSTRACT FROM AUTHOR]

Objective: Ischemic stroke is one type of circulatory disturbance caused by blood clots that block blood flow to the brain. One of the impact of ischemia is nerve cell damage due to excitotoxicity. Inhibition of the ionotropic glutamate receptor such as the AMPA receptor, becomes an essential approach to the treatment of ischemia. This study aims to explore the possibility of an Indonesian herbal compound as an AMPA receptor antagonist. Methods: In this study, virtual screening of 2233 herbal compounds was performed by docking method using AutoDock to find the antagonist candidate of AMPA receptor from Indonesian herbal database. The virtual screening method was validated by an area under curve (AUC) of the ROC curve and enrichment factor (EF). Lipinski's Rule of Five was used to filter the screening result. Results: The validation of virtual screening result showed that AUC was 0.9385 and EF 1% was 23.5550. The screening result of Indonesian herbal database showed top five compound sanggenol O, blazeispirol X, progesterone, nimolicinol and boeravinone F (-8.51; -8.39; -8.19; -8.17; -8.08 kcal/mol, respectively) and have interaction with TYR61 and THR91 residues of AMPA receptor. Conclusion: Five compounds of the Indonesia herbal database were shown as hits of AMPA receptor antagonist based on the docking method. [ABSTRACT FROM AUTHOR]

Objective: Nowadays, There hasn't any three-dimensional (3D) chemical structure database yet for biologically active compound in sponges from Indonesian origin. Therefore, this study aimed to create in silico a 3D-structure database of such compound and to evaluate the preferred software for this purpose. Methods: 2D- structure of selected compounds was established using MarvinSketch software. Conversion from 2D- into 3D-structures was evaluated by comparing MarvinSketch, OpenBabel and VegaZZ software packages. Visualization of the respective 3D-structures was perfomed by using PyMOL software. From 68 scientific articles, 212 chemical compounds were selected from 53 Indonesian sponge species. Results: The conversion of 2D-structures of the selected 212 chemical compound into 3D-structures lead to 7118 files, respectively consisting of 2508 files from the MarvinSketch, 1672 files from the OpenBabel and 1051 files from the VegaZZ software. The results based on the extention files were 1043 SDF, 1258 MOL and 2930 PDB format files of the three-dimensional structure. The valid and correct three-dimensional structure of chemical compound were 914 .sdf format files, 916 format .mol files and 72 .pdb format files. From the three-dimensional structures visualization, the database prefers established by using MarvinSketch with SDF or MOL format files since the results is consistent to literature and contain less number of errors. [ABSTRACT FROM AUTHOR]

Objective: Development of novel drugs is an important challenge in the pharmaceutical world and industry. In-silico methods are often considered in refinement / correction processes of drug design because they may lower the costs. The in-silico drug discovery process requires a three- Dimensional Structure (3DS) of the chemical compounds as input. Computational 3DSs often exhibit structural mismatches thus affecting the validity of the in-silico drug design process. In a previous study, a 3DS database with 1405 of Indonesian herbal compounds was developed, named HerbalDB. In this database, various structural mismatches were identified in some of the 3DSs. Our study aimed to identify and correct the structural mismatches in the herbalDB and to determine the best method in creating correct 3DS of chemical compounds. Methods: Structural mismatches in the herbal database were identified by molecular visualization. Results: The identification process yielded 170 compounds with structural mismatches that were corrected with 10 different parameters using the MarvinSketch and VegaZZ software, evaluated by molecular visualization. Conclusions: based on 3DS of chemical compound visualization, *.mol and *.sdf file format created using Dreiding force fields of MarvinSketch are the best method to construct the proper structure of Indonesian medicinal plant's chemical compound database compared with MMFF94, AMBER and CHARMM forcefields. [ABSTRACT FROM AUTHOR]

Objective: Previous research found that Adenosine A2A antagonist allows to reduce motor fluctuations, dyskinesia, protect from neurodegenerative disorder in Parkinson's disease in the human brain which is chronic progressive of losing dopaminergic neurons. The aim of this study is to explore Indonesian herbal compounds as Adenosine A2A inhibitor using virtual screening method. Methods: In this study, virtual screening of Indonesian herbal database as Adenosine A2A inhibitor was done by AutoDock and AutoDock Vina and was validated by database from A Directory of Useful Decoys: Enhanced (DUD-E). The method was validated by Enrichment Factor (EF) and Area Under Curve (AUC) of Receiver Operating Characteristics (ROC) curve Results: Based on the validation results, grid box that was used in virtual screening using AutoDock is 60 x 60 x 60 with EF1% 16.5869 and AUC 0.8406. The two compounds Chitranone and 3-O-Methylcalopocarpin with binding energy -10.19 and -9.55 kcal/mol, respectively showing interaction with Adenosine A2A active site at residues ALA63, ILE66, ALA81, LEU85, PHE168, GLU169, MET177, TRP246, LEU249, ASN253 and ILE274. Conclusions: This study concludes that Chitranone and 3-O-Methylcalopocarpin could be proposed to be developed as Adenosine A2A antagonists. [ABSTRACT FROM AUTHOR]

Objective: To isolate, identify, and evaluate a new angiotensin-converting enzyme inhibitor from Peperomia pellucida (L.) Kunth herbs. Methods: A dried sample of Peperomia pellucida herb was successively macerated with n-hexane and ethyl acetate. The ethyl acetate extract solution was evaporated to obtain the crude extract. Vacuum liquid column chromatography and thin layer chromatography were performed to obtain two pure compounds. Then, both compounds were elucidated and identified using the spectroscopic method. Angiotensin-converting enzyme inhibitory activity studies of both compounds were determined using angiotensin-converting enzyme kit WST-1 with spectrophotometer microplate reader 96-well at 450 nm wavelength. Results: Two bioactive compounds were successfully isolated from Peperomia pellucida herb, including a new compound of 2,3,5-trimethoxy-9-(12,14,15-trimethoxybenzyl)-1H-indene and pellucidin A. Both compounds demonstrated angiotensin-converting enzyme inhibitory activity, with IC50 values of 72 μM (27.95 μg/mL) and 11 μM (4.4 μg/mL), respectively. Conclusions: In the present study, two active angiotensin-converting enzyme inhibitors were successfully isolated and purified from Peperomia pellucida which is used as an antihypertensive in traditional medicine, and support its use as an angiotensin-converting enzyme-inhibiting drug. [ABSTRACT FROM AUTHOR]

[Display omitted] Pluchea indica leaves (PIL) is a polyphenolic-rich plant. Polyphenols, such as phenolics and flavonoids, are natural antioxidants. This study aims to evaluate the ability of natural deep eutectic solvent (NADES) based on ultrasonic-assisted extraction (UAE) for highly efficient extraction of the polyphenolic antioxidant compounds from PIL. Choline chloride-urea (ChCl-U) was selected based on screening of 17 types of NADES. This study uses Response Surface Methodology (RSM) to help determine optimal extraction conditions. The selected variables include molar ratio, temperature, and the water addition in the NADES. The responses used for the RSM study were total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing power (RP) methods with microtiter analysis. The best condition for polyphenolic antioxidants extraction using ChCl-U NADES was a 1:3 molar ratio, temperature of 52 °C, and 26% of water addition in NADES. Under these conditions, the extraction of total phenolics and flavonoids from PIL with antioxidant activity increased up to 1.2 folds and 3.1 folds compared with 50%-ethanol and methanol, respectively. The morphology of the leaves before and after extraction was also evaluated with a scanning electron microscope (SEM) to observe the effects of ultrasonic vibrations with different solvents. Furthermore, the compound di-caffeoylquinic acid (DCQA) in PIL was selectively found in ChCl-U extract through quadrupole time-of-flight mass spectrometry (UPLC-QToF-MS/MS) analysis. Thus, ChCl-U combined with UAE can be developed for polyphenolic extraction from PIL for extract production as an antioxidant. [ABSTRACT FROM AUTHOR]

Background: Murine Double Minute-2 (MDM2) overexpression causes the p53 deficiency, so the role p53 as a cell regulator does not work in the case of cancer. Methods: In this study, virtual screening of Indonesian herbal database to discover MDM2 inhibitors was carried out. Autodock and Autodock Vina validated with Directory of Useful Decoy-Enhanced (DUD-E). Validation parameters were performed with Enrichment Factor, Receiver Operating Characteristics, and Area Under Curve. Results: The validation with the grid box 70x70x70 on Autodock resulting AUC value 0.72, while in Autodock Vina 0.43. Autodock Vina did not fulfilll the standard value but still used for comparison. Based on the virtual screening result, top ten compounds from Autodock are Nimolicinol, Jacoumaric acid, Isoarborinol, Lantic acid, Diosgenin, Theasaponin E1, Taraxasterol, Leucadenone C, Simiarenol, and Alpha-Amyrin were found to have strong interaction with MDM2, with binding energy (ΔG) ranging from -8.83 to -9.65 kcal/mol. The Autodock Vina screening resulted in the identification of Yuehchukene, Morusin, Cyanidin, Leucadenone C, Roxburghine-B, Ocidentoside, Beta-sitosterol, Curine, Withangulatin, and Jacoumaric acid as potential inhibitors with binding energy (ΔG) ranging from -8.7 to -9.4 kcal/mol. Conclusion: Jacoumaric acid and Leucadenone C were shown to interact with the active site in MDM2 at residues Leu54, Ile61, Met62, and Ile99. [ABSTRACT FROM AUTHOR]

Background: Phyllanthus niruri, in Indonesia, is known as “Meniran” has a long history of use in ethnic or traditional medicine worldwide, mainly as an antihypertensive agent. Objective: The present study was designed to isolate and identify active compounds with angiotensin-converting enzyme (ACE) inhibition activity from P. niruri herb and confirm the mechanism of action, affinity, and domain specificity interactions of the isolated compounds. Materials and Methods: Some fractions of P. niruri methanolic extract were subjected to column chromatography and preparative thin-layer chromatography to get active compounds. Structural elucidation was determined via spectroscopic methods. ACE inhibition activity was measured using hippuryl-L-histidyl-L-leucine as a substrate in vitro assay. Furthermore, confirmation of the mechanism of action, affinity, and domain specificity interaction of the isolated compounds on ACE complex macromolecule (protein database id: 1O86) was performed by in silico molecular docking studies. Results: In this work, four active compounds were isolated from aerial part of P. niruri, including hypophyllantin (50% inhibition concentration [IC50] = 0.180 μg/mL), phyllantin (IC50 = 0.140 μg/mL), methyl gallate (IC50 = 0.015 μg/mL), and quercetin 3-O-β-D-glucopyranosyl-(1'''-6'')-α-rhamnoside (IC50 = 0.086 μg/mL). In silico molecular docking method emphasizes ligand-residue interactions, thereby predicting the inhibitory activity of these compounds. After docking to an ACE complex macromolecule, quercetin 3-O-β-D-glucopyranosyl-(1'''-6'')-α-rhamnoside obtained more interactions than lisinopril. Conclusion: The results were obtained from in silico and in vitro experiments and confirm the potential active compound is an ACE inhibitor and a new antihypertensive agent. Abbreviations Used: P. niruri: Phyllanthus niruri; ACE: Angiotensin-converting enzyme; HHL: Hippuryl-L-histidyl-L-leucine; HA: Hippuric acid; PDB: Protein database; IC50: 50% inhibition concentration; FH: N-hexane fraction; FE: Ethyl acetate fraction; TLC: Thin layer chromatography; UV-VIS: Ultraviolet-visible; NMR: nuclear magnetic resonance; FTIR: Fourier–Transform infrared; MS: Mass spectrometry; HMQC: Heteronuclear Multiple-Quantum Correlation; HMBC: Heteronuclear multiple bond correlation; TADOK: Tugas Akhir Mahasiswa Doktor. [ABSTRACT FROM AUTHOR]

A multivariate analysis of the quantitative relationship of antioxidant structure and activity of a series of benzoic acid derivatives based on computational chemical properties was calculated. The parameters were obtained from the optimized structure of ionization pKa and hydrophobic ClogP while the compound activity was obtained from the literature. Analysis of the relationship between antioxidant activity and chemical properties of the compound was performed with the SPSS 21 program. The analysis result gives the best equation model as follows: Log 1/IC50 = -1.514 + 0,516 log P + 0.087 pKa (n = 10 r = 0,962 SE = 0,301 Fcalc./Ftable = 1,422). [ABSTRACT FROM AUTHOR]

Objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitor had been evaluated in clinical trials as the basic strategy of hyperglycemia handling in diabetes. However, because of SGLT2 inhibitors is the new class of oral antidiabetic, it is rare to be found in Indonesia, and it is costly.This study was intended to find compounds from Indonesian herbal database that show capability to be used as SGLT2 inhibitors through a pharmacophore-based virtual screening approach. Methods: The SGLT2 inhibitor pharmacophore models were made from 10 training sets of SGLT2 ligand inhibitors using the Ligand Scout 4.1.5. Ten pharmacophore models which had been made were validated using test set and decoy set methods to know how the performance of pharmacophore model worked. Virtual screening were then applied to the best pharmacophore model. Results: The model-1 pharmacophore was the best model, with values of 0.9080, EF1% = 56.5, EF5% = 56.5 and AUC100% = 0.87 which served as model for virtual screening. Model-1 consisted of one hydrophobic interaction, one aromatic ring, four hydrogen bond donors and five hydrogen bond acceptors. Virtual screening showed three compounds (Hits) with best pharmacophore fit scores according to model-1 among 1377 compounds, they were vitexin = 113.62; cucumerin A = 112.62; and cucumerin B = 113.51. Conclusion: These results showed that vitexin, cucumerin A, and cucumerin B potentially have activity as an SGLT2 inhibitor. [ABSTRACT FROM AUTHOR]

Objective: Gnetum gnemon L. (melinjo) seed extract contained trans-resveratrol which has been shown to inhibit hydroxymethylglutaryl-CoA (HMG-CoA) reductase. Therefore it has a potent activity for lowering blood cholesterol. This study was carried out to determine the molecular dynamics simulation of HMG-CoA reductase inhibitors from Gnetum gnemon L. seed extract. Methods: Molecular dynamics simulation using AMBER was used. The simulation was set at 300 K as default temperature and 310 K, average human body temperature. The main parameters of this study were ligand-residue interaction, binding affinity, root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonds analysis, molecular mechanics Poisson Boltzmann surface area (MMPBSA), and molecular mechanics generalized born surface area (MMGBSA). Results: In the simulation study, trans-resveratrol, trans-piceid, gnemonol M, gnemonoside B, viniferin and gnetin C had shown lower energy than HMG (PDB ID: MAH), the substrate of HMG-CoA Reductase. Free energy binding obtained from simulation was between 11.1 to -31.38 kcal/mol. Conclusion: The simulation at 310 K was preferable than 300 K as more interactions were performed and higher affinity was obtained. [ABSTRACT FROM AUTHOR]

Background: One of the major antioxidants in Myrmecodia pendens (sarang semut) tubers is anthocyanin. Objective: To obtain antioxidant activity and anthocyanin concentration from sarang semut optimally through an appropriate method. Materials and Methods: Microwave-assisted extraction (MAE) was chosen because of its brief extraction time (ET), saving solvents, and being inexpensive compared to conventional extraction methods. Experiment design was prepared using response surface methodology. 1,1-diphenyl-1-2-picrylhydrazyl and reducing power method were used for the determination of the antioxidant activity, while the Association of Analytical Communities official method 2005.02 was used for the anthocyanin concentration calculation. Results: It was found that the optimum antioxidant activity was obtained at 80% ethanol, sample-to-solvent ratio (S/S ratio) 1:12, ET 10 min, and MAE power 50%. Meanwhile, the optimum anthocyanin extraction was obtained at 80% ethanol, S/S ratio 1:8, ET 3 min, and MAE 10%. Conclusion: The optimum condition of antioxidant activity and anthocyanin concentration was the same at the solvent used, yet different at the S/S ratio, ET, and power level which open further research to support this study. Abbreviations Used: S/S ratio: Sample-to-solvent ratio, ET: Extraction time, MAE power: Microwave-assisted extraction power, RSM: Response surface methodology. [ABSTRACT FROM AUTHOR]

Objective: Gnetum gnemon L. (melinjo) seed extracts have been known to have some biological activities. One of them is ACE (angiotensinconverting enzyme) inhibitor. The present study was conducted to predict potential ACE inhibitory activity of several compounds isolated from Gnetum gnemon L. seeds by using in silico method. Methods: In this study, several compounds isolated from melinjo seeds were determined for their ACE inhibitory activity through molecular docking study and molecular dynamics simulations. Molecular docking experiment was performed by using AutoDock4Zn. Subsequently, molecular dynamics simulations using AMBER within 20 ns was conducted to analyze the interactions stability between zinc-ligand and ligand-amino acids in the active site of ACE since both of these mechanisms were known to play essential roles to inhibit ACE. Results: The results showed that resveratrol, gnetol, isorhapontigenin, gnetin C, trans-e-viniferin, gnemonol K, gnemonol M and aglycone of gnemonoside B exhibited G values which were lower than or close to lisinopril, captopril, and enalaprilat. Some of these ligands were able to bind zinc ion via cation-pi interactions. According to the free-energy binding calculations using MM-GBSA and MM-PBSA methods, gnetin C showed the highest affinity for ACE among other ligands at a temperature of 300 K, while at a temperature of 310 K the highest affinity was exhibited by gnemonol K. Conclusion: According to the molecular docking and molecular dynamics simulations, several compounds isolated from melinjo seed showed potential ACE inhibitory activities, in which gnemonol K promised as the most potential compound to have ACE inhibitory activity. [ABSTRACT FROM AUTHOR]

Introduction: According to International Agency for Research on Cancer (IARC), the number of lung cancer patients has reached 1.8 million lives, and 85% of the number contribute to non-small cell lung cancer. In the past years, research on targeted therapy has been developed due to its efficacy and a small number of side effects. Research on marine fungi compounds has not been explored to non-small cell lung cancer therapy. Methods: This research uses molecular dynamics simulation method to marine fungi compounds that have been docked to EGFR (FU0015, FU0051, FU0202) and VEGFR-2 (FU0033) as antiproliferative and antiangiogenetic agent by inhibition activity using AutoDock and AMBER at 300K and 310K temperature using EGFR (Gefitinib, Erlotinib, and Imatinib) and VEGFR-2 (Nicotinamide and Vatalanib) as reference standards. Results: Molecular dynamics results for EGFR inhibitors at 310K shows the best MMGBSA free energy and hydrogen occupancy in FU0051 (-43.72 kcal/mol; 98.80%) followed by FU0202 (-31.64 kcal/mol; 43.35%), and FU0015 (-15.55 kcal/mol; 3.35%). FU0033 fungi as a material for VEGFR-2 inhibitor shows higher MMGBSA free energy in comparison to its reference standards and low hydrogen occupancy (0.15%) at 310K. Conclusion: This research shows that FU0051 and FU0202 have potential to be an antiproliferative agent candidate, hence in vitro test should be obtained. [ABSTRACT FROM AUTHOR]

Objective: Cancer is a disease that can occur because of apoptosis failure. One of the causes of apoptosis failure is the presence of MDM2 inhibiting the activity of p53 so procaspase-3 could not be activated to caspase-3. Currently, the treatment of cancer has been applied widely, but more effective treatment always needed because cancer has been mutated. One of the treatments is the search for natural resources that come from the sea. The pursuit of the bioactive compound from marine organisms is not straightforward because it takes a long time and costly. Methods: Therefore, in silico method is used. This study conducted a docking of bioactive compounds from saponin and 2, 5-Piperazinedione as the MDM2 inhibitor and procaspase-3 activator by using Auto Dock and Vina. Results: The results showed that 18-Oxotryprostatin A and Intercedenside A were the best bioactive compounds to serve as MDM2 Inhibitor and 6-Methoxyspirotryprostatin B and Frondoside A as a procaspase-3 activator due to their low binding energy. Conclusion: Most recommended bioactive compounds are those who have low binding energy, which is 18-Oxotryprostatin A with the value of -8, 6 kcal/mol and Intercedenside A with the value of -7, 0 kcal/mol. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to observe the difference of extraction method (both conventional and non-conventional) based on metabolite profile using UPLC-QToF-MS/MS system from Peperomia pellucida (L.) Kunth. Methods: Dried samples were extracted using the conventional maceration method and the optimum ofionic liquid-based microwave-assisted extraction (IL-MAE) methods. Metabolite profiling was performed using UPLC-QToF-MS/MS system with some modifications adjusted to the instrument condition. The data was analyzed using Masslynx 4.1 software. Results: based on the results, there were differences on metabolite profiling from both conventional and non-conventional extraction methods that was extraction method using organic solvent and ionic liquid solvent ([BMIM]BF4 at the optimum condition. The extract obtained using IL-MAE method had a peak depth with a well-separated Rt (retention time) value ranging from 0.5 to 7.5 min which means that the extracted compound was from polar to nonpolar properties. The extract obtained using maceration method, the peak spread on a separate Rt ranges from 2.5 to 7.5 min. Also, both extracts obtained have different area under curve (AUC) values with amount total of 22285 (IL-MAE) and 12679 (maceration), respectively, and showed the IL-MAE twice as large as that of the maceration. Conclusion: based on the results, conventional and non-conventional extraction method showed differences in metabolite profiling based on Rt value and mass spectrum m/z of each peak. [ABSTRACT FROM AUTHOR]

Objective: The hepatitis B virus (HBV) core protein was chosen as receptor target for a new, selective and effective due to resistance of current hepatitis B drugs against reverse transcriptase. It forms the capsid of viral particles and essential for viral genome DNA replication and maturation. Emodin was known showing inhibitory effect on HBV replication weakness, but persistent both in vitro and in vivo so still need modification. In this study, emodin derivatives were conducted as an inhibitor candidate of capsid assembly by disruption formation dimer-dimer HBV core protein using molecular docking and dynamic simulation. Methods: Structure-based virtual docking approach was used to design of benzoylated emodin derivatives into HBV core protein as receptor using Molegro Virtual Docker 6.0 program. The stability of interacting residues of proteins with compounds was identified via molecular dynamics and free binding energy calculations using Amber 12. Results: The ligand binding site in an HBV core protein was an interfacial hydrophobic pocket and placed at the dimer-dimer of the core protein interface. Interactions between emodin and derivatives indicated by hydrogen bonding and steric interaction between the ligand with the amino acid residues in the HBV core protein. It is predicted that viral replication would inhibit due to a change in orientation of capsid assembly by core proteins. The benzoylated emodin derivatives showed promising inhibitory profiles better than emodin which were indicated by their binding scores were more negative. Conclusion: This study provides a basis for further chemical design for more effective derivatives of emodin derivatives. [ABSTRACT FROM AUTHOR]

Objective: This research was conducted to screen inhibition of HIV-1 reverse transcriptase activity of selected Indonesia medicinal plants and to isolate HIV-1 reverse transcriptase inhibitor from Erythrina variegata leaves. Method: Screening inhibition of HIV-1 RT activity of selected Indonesia medicinal plants and isolated compounds were performed using HIV-1 RT colorimetric assay. The isolation of HIV-1 reverse transcriptase inhibitor was conducted using chromatography technique. The isolated compound was determined based on the data of UV, IR spectrophotometry, MS, 1D and 2D NMR spectroscopy. Results: Beside that, in vitro study of the leaves methanolic extract exhibited inhibition against HIV-1 RT activity with percent inhibition of 97.64% at concentration of 5 mg/mL. Ethyl acetate fraction from the extract showed the strongest HIV-1 RT inbitory activity with IC50 of 429.28 μg/mL. Isolation the HIV-1 RT inhibitor from the fraction give compound 1. Conclusion: Erythrina variegata leave extract exhibited potent inhibition on HIV-1 RT activity. The isolated compound from the leaves was determined as apigenin-7-O-β-D-glucopyranoside and demonstrated HIV-1 RT inhibitory activity with the IC50 value of 100.59 μg/mL. [ABSTRACT FROM AUTHOR]

Objective: This study aims to synthesize a series of five new Mannich bases of dehydrozingerone (DHZ) derivatives and to evaluate for their antiinflammatory and antioxidant activity. Methods: The synthesis was performed by refluxing DHZ with formaldehyde and secondary amines, and the structures of the synthesized compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR, and HR-MS. The anti-inflammatory and antioxidant activity evaluations were done by inhibition of heat-induced albumin denaturation and a free-radical DPPH method, respectively. Results: All the synthesized compounds (2a-e) showed anti-inflammatory and antioxidant activity. The highest anti-inflammatory activity was shown by compound 2c. The activity was comparable to the that of diclofenac sodium as a standard. While, the highest antioxidant activity was demostrated by compound 2e. The compound showed moderate activity compared to that of quercetin as a standard. Mostly of Mannich base derivatives of DHZ compounds exhibited higher antioxidant activity than that of DHZ. Conclusion: A series of five new Mannich bases of DHZ (2a-e) was synthesized successfully. Compound 2c demonstrated anti-inflammatory activity which was comparable to diclofenac sodium, while compound 2e exhibited moderate antioxidant activity compared to quercetin as standard. [ABSTRACT FROM AUTHOR]

Background: Ionic liquid-based microwave-assisted extraction (IL-MAE) is one of the non-conventional extraction methods that has been developed and applied in recent years. Some studies have reported the success of this approach for extracting the target compound (secondary metabolites) from medicinal plants optimally. Objective: This review paper aimed to provide detail information about the application of the IL-MAE method as a fast and green extraction of a secondary metabolite from the medicinal plant. Materials and Methods: The literature published on IL-MAE was searched and collected using online resources from the electronic databases including Google Scholar, DOAJ, PubMed, ScienceDirect, and Scopus. Results: This review highlights the role of IL as a green solvent, the basic principles, mechanisms of MAE, and its utilization of natural product extraction. Furthermore, this review explained about the application of the IL-MAE method to extract secondary metabolite (particularly the targeted compound) from a medicinal plant, and a brief extraction mechanism of IL-MAE using Fourier-transform infrared spectroscopy and scanning electron microscopy. Conclusion: The application of IL-MAE method has successfully performed to extract the targeted secondary metabolite from a natural product, where the extraction process to be rapid, efficient, and green. [ABSTRACT FROM AUTHOR]

Objective: Nowadays, many researchers focused on finding and developing the new inhibitor of HDAC4 and HDAC7 using in silico tools such as docking, pharmacophore approaches, and molecular dynamics simulation. The aim of this research is to identify pharmacophore of HDAC4 and HDAC7. Method: In this research, pharmacophore-based virtual screening was used to find new HDAC4 and HDAC7 inhibitor from Indonesian herbal database. From MUBD-HDACs database, active compounds of HDAC4 and HDAC7 were divided into training and test set. Based on pharmacophore model generation for HDAC4 and HDAC7, 10 models were created. All the models were calculated and evaluated using some parameters of validation. Results: The best pharmacophore model for HDAC4 are model 6 and 10, and for HDAC7 is model 1. Pharmacophore model 6 and 10 (HDAC4) have seven pharmacophore features include three HBA, one HBD, one aromatic ring, one negatively ionizable area and 1 hydrophobic. Pharmacophore model 1 (HDAC7) have five pharmacophore features include two HBA, one HBD, one negatively ionizable area and one hydrophobic. These selected models for HDAC4 and HDAC7 were using for virtual screening against Indonesian herbal database. Conclusion: Based on the results of the virtual screening, six hit compounds were obtained such as artocarpesin, avicularin, dimboa glucoside, eriodictin, luteolin and mirabijalone c. [ABSTRACT FROM AUTHOR]

Objective: Sirtuins are protein deacetylases regulating cellular metabolism, lifespan, stress responses, and linked with diseases pathogenesis such as cancer and neurodegenerative diseases. SIRT1, one of human seven sirtuins, the most widely studied today. Hence, identification of SIRT1 drug compound has attracted in drug discovery community. To find good drug candidates could use in insilico methods as a quick tool for analyzing the biological activity of drugs virtually. Method: In silico methods in this research using molecular dynamics simulations that use Indonesia herbal database to identification hits compounds as the SIRT1 inhibitor. Analysis of molecular dynamics simulations in this study includes RMSD (root mean square deviation), RMSF (root mean square fluctuation), molecular mechanism Poisson-Boltzmann/surface area (MMPBSA) and hydrogen bonding. Results: The results showed that hits compounds, dregamine and 5-oxocoronaridine against two of macromolecules SIRT1 (PDB ID: 4I5I and 4ZZI) obtained free energy MMPBSA calculation about -23 kcal/mol Meanwhile occupancy hydrogen bonding of residues Ile347 and Asp348 about 80%. Conclusion: Hits compounds dregamine and 5-oxocoronaridine against two of macromolecules SIRT1 inhibitor (PDB ID: 4I5I and 4ZZI) obtained free energy MMPBSA calculation about -23 kcal/mol meanwhile occupancy hydrogen bonding of residues Ile347 and Asp348 about 80%. [ABSTRACT FROM AUTHOR]

The invention of graphical processing units (GPUs) has significantly improved the speed of long processes used in molecular dynamics (MD) to search for drug candidates to treat diseases, such as malaria. Previous work using a single GTX GPU showed considerable improvement compared to GPUs run in a cluster environment. In the current work, AMBER and dual GTX 780 and 970 GPUs were used to run an MD simulation on the Plasmodium falciparum enoyl-acyl carrier protein reductase enzyme; the results showed that performance was improved, particularly for molecules with a large number of atoms using single GPU. [ABSTRACT FROM AUTHOR]

Objective: The aims of the study was to explore the application effect of ionic liquid as a green solvent in the polyphenolics content extraction from Peperomia pellucida (L.) Kunth herbs using 1-butyl-3-methyl imidazolium bromide ([BMIM]Br) and 1-butyl-3-methyl imidazolium chloride ([BMIM]Cl). Methods: The polyphenolics content extraction was performed by using the ionic liquid based microwave-assisted extraction (IL-MAE) method with some extraction parameters, including extraction time, microwave power, ratio liquid-solid, and ionic liquid concentration. The yields of total polyphenolic content were examined using a microplate reader 96 well method, and the extraction mechanism was analyzed using scanning electron microscopy (SEM). Results: The results showed that the effect of ionic liquid on the yield of total polyphenolics content, including 18.287 µg GAE/g (0.7 mol/l [BMIM]Cl concentration, 14 ml/l liquid-solid ratio, and 270 Watts microwave power for 10 minutes), and 15.734 µg GAE/g (0.7 mol/l [BMIM] Br concentration, 14 ml/l liquid-solid ratio, and 270 Watts microwave power for 15 minutes), whereas the SEM demonstrated the extraction mechanism with significant physical changes in matrix sample after treatment using different solvents. Conclusion: Application of green chemistry principles using an ionic liquid as a green solvent for the polyphenolic extraction of P. pellucida herbs to be rapid, easy, and efficient. [ABSTRACT FROM AUTHOR]

Objectives: Melinjo (Gnetum gnemon) seeds have been known to have some biological properties. One of them is ant hypercholesterolemia. The present study investigated in vitro and in silico methods to predict potential antihypercholesterolemic of the Melinjo seed extracts of through HMG-CoA reductase inhibitory activity. Methods: Melinjo seed powders were successively extracted by reflux method using five solvents with gradient polarity including: n-hexane, dichloromethane, ethyl acetate and methanol. All extracts were evaluated in vitro using HMG-CoA Reductase assay kit, to analyze the inhibitory activity. Molecular docking of the phytochemical content of the seeds were carried out using Auto Dock Vina, and also Ligand Scout to analyses interaction between ligand and receptor. Results: Dichloromethane extract demonstrated the highest inhibitory activity against HMG-CoA reductase with IC50 value is 0.40 µg/mL, followed by that of ethyl acetate extract. UPLC-MS analyses showed that dichloromethane extract contained trans-resveratrol, piceid, gnetin C, gnetol, isorhapontigenin, ε-viniferin, gnemonol L, and gnemonol M. Molecular docking studies demonstrated that dimer of resveratrol such as gnemonol L, gnemosida, and ε-viniferin have better free binding energy than that of monomer. piceid, gnetin C, gnemonol L, and gnemonol M could be considered as HMG-CoA reductase inhibitor. Conclusion: Gnetum gnemon seed extract showed strong HMG-CoA reductase activity. Resveratrol dimer promises as a potential lead compound to design/synthesize anti-cholesterol. [ABSTRACT FROM AUTHOR]