AutoDock Research Articles

Isolation, In-silico Studies, and Biological Evaluation of Higenamine from Annona squamosa L. against Breast Cancer

The efficacy of Annona squamosa L. in cancer treatment has been documented, inspiring the authors to investigate the plant further for potential novel anticancer compounds. Therefore, the current study aimed to isolate and characterize Higenamine from leaves extract of A. squamosa L. and studied for the in-vitro cancer cell line and molecular docking. The high performance liquid chromatography (HPLC) and thin layer chromatography (TLC) method development of A. squamosa L. leaves extract furnished Higenamine of which characterization was established by HPLC, infrared radiation (IR), liquid chromatography-mass spectrometry (LC-MS) and its acute toxicity study and cytotoxic properties using MCF-7 cell lines by MTT assay were assessed. Molecular docking was done using Auto Dock Vina software to validate the anticancer activity. The extraction batches by ultrasonication and maceration methods showed good results using 80% methanol. Acute toxicity studies, after a single dose (2000 mg/kg) administration of methanolic extract don’t show clinical symptoms of toxicity and mortalities. From the extract, Higenamine was eluted and the dried fraction showed 66% of enrichment of Higenamine. The developed HPLC and TLC methods showed Higenamine (HGN) peak at 6.21 minutes band at Rf 0.61, respectively. The isolated compound was identified as Higenamine with FTIR spectroscopic analysis which revealed various characteristic band values with functional groups. HPLC-MS showed m/z at 272.1 (M+H+) corresponding to the molecular formula C16H17NO3. The IC50 value for Higenamine was 42.39 μg/mL were observed in MCF-7 breast cancer which was better than 5-Fluorouracil having 39.22 μg/mL. In-silico studies explored that higenamine showed good binding affinity to breast cancer PDBIDs and forms a stable complex. Furthermore, absorption, distribution, metabolism, and excretion (ADME) properties of isolated compound was calculated using the Swiss ADME online tool in which higenamine was found to have a good pharmacokinetic profile as compared with 5-fluorouracil and doxorubicin. Higenamine has been isolated and identified as a potential anticancer agent. Further research can explore its effectiveness through pharmaceutical formulation and in vitro cell line studies.

Mechanism of Valeriana Jatamansi Jones for the treatment of spinal cord injury based on network pharmacology and molecular docking.

Spinal cord injury (SCI) is characterized by high rates of disability and death. Valeriana jatamansi Jones (VJJ), a Chinese herbal medicine, has been identified to improve motor function recovery in rats with SCI. The study aimed to analyze the potential molecular mechanisms of action of VJJ in the treatment of SCI. The main ingredients of VJJ were obtained from the literature and the SwissADME platform was used to screen the active ingredients. The Swiss TargetPrediction platform was used to predict the targets of VJJ, and the targets of SCI were obtained from the GeneCards and OMIM databases. The intersecting genes were considered potential targets of VJJ in SCI. The protein-protein interaction network was constructed using the STRING database and the hub genes of VJJ for SCI treatment were screened according to their degree values. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape database. Cytoscape software was used to construct the "herb-ingredient-target-pathway" network. Preliminary validation was performed using molecular docking via Auto Dock Vina software. A total of 56 active ingredients of VJJ, mainly iridoids, were identified. There were 1493 GO items (P < .01) and 173 signaling pathways (P < .01) obtained from GO and Kyoto Encyclopedia of Genes and Genomes enrichment, including the phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, hypoxia-inducible factor 1 signaling pathway, and tumor necrosis factor signaling pathway. Molecular docking revealed that 12 hub genes enriched in the PI3K/Akt signaling pathway had a high binding affinity for the active ingredient of VJJ. VJJ may exert its therapeutic effects on SCI through the iridoid fraction, acting on signal transducer and activator of transcription 3, CASP3, AKT1, tumor necrosis factor, mammalian target of rapamycin, interleukin 6, and other hub genes, which may be related to the PI3K/Akt signaling pathway.

Bioinformatics Based: in Silico Docking Analysis of Polyherbal Formulation for The Management of Parkinson’s Disease (Nadukku Vatham)

Background: The discipline of Siddha medicine, particularly herbal formulations, can benefit greatly from the use of molecular docking because it enables the molecular interactions of the formulation’s lead molecules with receptors to be understood, as well as the inference of the formulation's basic biochemical targets. Aim: The goal of this study is to carry out an In-silico computational analysis of the phytochemicals found in Kuruver Kudineer (KK), a traditional Siddha remedy that is used for managing behavioral deficit in Parkinsons disease. Methodology: The ligand structures were developed and optimized using Auto Dock Tools (Morris, Goodsell et al., 1998). Using Auto dock Vina, the compounds were all docked. The function of the target protein Monoamine Oxidase -A (PDB 2Z5X), which is involved in the breakdown of the neurotransmitters by MAO-A, will be inhibited by the creation of a hydrogen bond between phytocomponents and the target's core amino acids (Tyr 69, Ile 335, Tyr 407, and Tyr 444). In order to control the dopamine level, phytocomponents that inhibit the target enzyme MAO-A may be used as potential targets. Results: The compounds present in Kuruver Kudineer (KK) like Gingerenone-A, Betulinic acid, Zingiberene, Rutin, Geniposide and β-sitosterol showed maximum interactions with MAO –A when compared to that of Clorgyline. According to the outcomes of the computational investigation, the bio-active substances present in the Siddha formulation Kuruver Kudineer (KK) have significant affinity to the target MAO-A (PDB 2Z5X). Conclusions: From the results of the present study, it was concluded that the MAO – A reveal significant effect to managing the behavioral deficit and thereby considered an excellent drug choice for the clinical management of Parkinson’s disease (Nadukku vatham)

Synthesis, antimicrobial and cytotoxic activities of tetrazole N-Mannich base derivatives: Investigation of DFT calculation, molecular docking, and Swiss ADME studies

Tetrazole derivatives are a prime class of heterocyclic compounds that are important for the design of drug molecules. In this study, the cytotoxicity and antimicrobial activity of a novel class of tetrazole N-Mannich base derivatives were investigated. The synthesised compounds were evaluated by FTIR, NMR spectroscopy, mass spectrometry, and elemental analysis. All synthesised compounds were investigated for antimicrobial activity; in particular, compound 2d was found to be more effective against S. aureus than cefazolin. Compound 2e was more effective than clotrimazole against Cryptococcus neoformans. All the synthesised compounds were investigated against cancer cell lines (HepG2, MCF-7, and HeLa); in particular, compound 2e was more active against the HeLa cancer cell line than doxorubicin. Synthesised compounds were studied for molecular docking interactions between proteins and synthesised molecules using the Auto Dock Vina 1.1.2 programme. According to molecular docking studies, 2d has a greater docking score (-6.4 kcal/mol) compared with cefazolin (-5.8 kcal/mol) for the 1BQB protein and 2e was equal docking score compared with clotrimazole (-2.3 kcal/mol) for the 3SFX protein. Density functional theory (DFT) was used to perform calculations for highly and low-active compounds in order to estimate the energy gaps 2e and 2d (∆E = 0.1, and 0.21 eV). Additionally, we discuss the role of the Swiss ADME tool in determining the physicochemical properties of all synthesised compounds. According to the results, the newly synthesised tetrazole derivatives may have medicinal importance and could be used as antibacterial agents.

Determination of phyto-moieties from the traditional therapeutic plant Boswellia serrata Roxb. extract against nosocomial pathogens: in vitro and silico approaches

IntroductionThe present study aimed to examine the in vitro antibacterial activity of Boswellia serrata solvent extracts against multidrug-resistant nosocomial pathogens isolated from skin and wound samples. MethodsB. serrata resin was acquired, and powdered; blended with five different extraction solvents. The collected bacterial isolates from wound and skin swabs were identified using biochemical profiling and classified according to their unique physiological and biochemical characteristics. Three isolated pathogens were exposed to antibiotic drugs via the disk dispersion assay, and the antimicrobial efficiency of the plant extract was assessed against the wound and skin infection-causing nosocomial bacterial pathogens. The qualitative and quantitative examination of plant extracts was carried out by mass spectra and 70 eV electron impact ionisation process. The 2D molecular interaction patterns between beta-lactamase protein and phytocompounds complexes were generated in DS viewer to understand the hydrogen bonding and hydrophobic interaction. ResultsThree antibiotic-resistant strains, Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, were isolated and exposed to the extract of B. serrata. Plant extract at 60 µg proven effective against antibiotic-resistant strains of S. aureus, P. aeruginosa, and A. baumannii. In molecular docking studies, it was found that out of the 15 bioactive compounds detected from the plant extract, only three showed significant binding affinity to the bacterial-lactamase protein (AmpC). The auto dock results revealed different crucial affinity values of the bioactive compounds. Cholan-24-oic acid, 3,12-bis(acetyloxy) showed a Dock score of −8.6 kcal/mol for P. aeruginosa, −8.1 kcal/mol for A. baumannii, and −7.6 kcal/mol for S. aureus. Due to its strong binding affinity with antibacterial target proteins, it exhibits exceptional antibacterial properties. ConclusionThe findings confirmed bioactive constituents in B. serrata, with antibacterial activity against antibiotic resistance nosocomial pathogens.

Unlocking the potential of aromatase inhibitors: recent advances in drug design, synthesis, docking activity, and in vitro bioactivity evaluations

Breast cancer, a global health concern claiming approximately 685,000 lives in 2020, necessitates continual advancements in therapeutic strategies. Estrogen and aromatase play pivotal roles in hormone-responsive breast cancer, with 80% of patients exhibiting estrogen receptor-positive tumors. Aromatase inhibitors (AIs), notably non-steroidal inhibitors like anastrozole and letrozole, have significantly improved outcomes, yet challenges persist, including side effects. This review focuses on recent developments in AIs, exploring xanthone derivatives, imidazole derivatives, and curcumin derivatives as potential inhibitors of aromatase. Molecular docking studies, employing Auto Dock and other tools, reveal the binding affinities and interactions of these compounds with the aromatase enzyme. Among xanthones, Erythrommone emerges as a potent inhibitor, holding promise for clinical trials. Imidazole derivatives, synthesized through the Debus-Radziszewski reaction, demonstrate anticancer potential, with compounds like 1a exhibiting superior efficacy against MCF7 cells. ADME-Tox analyses indicate promising drug-likeness but reveal potential mutagenic effects and environmental impacts. Curcumin derivatives, particularly 1,5-diaryl-1,4-pentadien-3-ones, present alternatives to address curcumin's bioavailability challenges. A study of 25 compounds (DKC) identifies DKC-10 as a potent inhibitor, outperforming established breast cancer drugs in terms of binding affinity and interactions with aromatase and ERα+ receptors. These findings underscore the importance of exploring diverse chemical structures in developing AIs, paving the way for more effective and well-tolerated therapeutics. The integration of computational techniques, such as molecular docking studies, accelerates drug discovery by predicting interactions at the molecular level. Overall, this comprehensive review provides valuable insights into the evolving landscape of aromatase inhibitors, offering a roadmap for future research and the development of advanced breast cancer therapeutics.

Tetrasiklin Antibiyotikleri ve Bromelain Enzimi Arasındaki Etkileşimlerin Kenetleme Araçları Kullanılarak İncelenmesi

Bromelain, extracted from the stem of the pineapple, is a complex enzyme used for different purposes. Bromelain supplements are often used to facilitate digestion, improve the circulatory system and relieve arthritis symptoms due to its pain relief. However, in some cases where there is a risk of antibiotic use or bleeding, the use of bromelain or direct consumption of pineapple should be limited. For this purpose, this study was carried out to show the mechanism by which the antibiotic bromelain interaction occurs. Firstly, the bromelain molecule and demeclocycline, minocycline, and tetracycline antibiotics were prepared in the UCSF Chimera visualizing program. The interactions were monitored in the Auto Dock Molecular Modelling Toolkit molecular modeling program. The free binding energies of these interactions were also calculated in Auto Dock. According the molecular modelling results, bromelain and demeclocycline, minocycline, tetracycline antibiotics were interact with hydrogen bonds and hydrophobic interactions. These interactions between bromelain and antibiotics were energetically favorable based on free binding energy calculations.

In Silico Insights into the Efficacy of Darjeeling Himalaya’s Traditional Fermented Beverages To Combat Various High-Altitude Sicknesses

Abstract This in silico study has been designed to validate ethnomedicinal properties of some Himalayan fermented ethnic beverages against varied high-altitude sicknesses. Traditional beverages like tongba, chhyang, nigar and finger-millet raksi (supplemented with ethnomedicines like khokim and chimphing) were considered in this study which were sampled from villages situated in Singalila Ridge of the Himalayas. Seven major metabolites such as ethyl alpha-D-glucopyranoside; meranzin; auraptene; cis-vaccenic acid; cyclo(pro-gly); cyclo(leu-pro); and 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one were investigated in silico to provide insights to their efficiency in alleviating major altitude illnesses (pulmonary edema and hypoxia); high-altitude respiratory infections; pain or inflammation; cardiovascular problems; gastrointestinal diseases and disorders; and high-altitude neurological diseases and disorders. Computational tools such as Molinspiration Chemoinformatics, SwissADME, Molsoft program and vNN-ADMET were employed to evaluate physicochemical properties, pharmacokinetics and ADMET parameters. Binding affinities were computed using Auto Dock Tools. In silico pharmacokinetics and ADMET revealed bioactivity potentials of selected metabolites which are associated to treat high-altitude sickness. A total of 175 combinations of receptor-ligand docking interactions were considered out of which 141 combinations exhibited a binding energy score of ≤ -5 and 29 combinations scored ≤ -7. Outcome of this computational research affirm the effectiveness of high-altitude’s traditional drinks in healing high-altitudinal stresses.

Network pharmacology and molecular docking to study the potential molecular mechanism of Qi Fu Yin for diabetic encephalopathy

Diabetic encephalopathy is a chronic complication of diabetes that lacks an optimized treatment strategy. The present study sought to elucidate the potential molecular mechanism of Qi Fu Yin in improving diabetic encephalopathy through network pharmacology. The active components and target information of Qi Fu Yin were obtained from the TCMSP and Swiss target databases, while the target information of diabetic encephalopathy was sourced from Gene cards, OMIM, and Pharm Gkb databases. Enrichment analyses of KEGG and GO were conducted utilizing drug-disease common targets, while protein-protein interactions were predicted through the utilization of the STRING database platform. Subsequently, molecular docking was executed via Auto Dock Vina to authenticate the interaction between core components and core targets. The findings revealed that Qi Fu Yin exhibited 178 common targets with diabetic encephalopathy, and the enrichment analyses demonstrated that these targets were associated with lipid and atherosclerosis, AGE-RAGE signaling pathways, and other related pathways. The findings of the molecular docking indicated a favorable binding affinity between the active components of drug and the core targets, with EGF and quercetin exhibiting the most notable docking score. Additionally, the molecular dynamics simulation corroborated this high affinity. These results suggested that the active ingredients of Qi Fu Yin, including quercetin and kaempferol, may modulated the expression of genes such as IL10, TNF, EGF, and MMP2, thereby activating the AGE-RAGE signaling pathways and potentially serving as a therapeutic intervention for diabetic encephalopathy. Communicated by Ramaswamy H. Sarma

A comprehensive compatibility study of ganciclovir with some common excipients

Objectives: The aim of the present study is to illustrate compatibility testing of ganciclovir (GCV) with some common excipients that would be used to manufacture solid oral dosage forms. Different spectroscopy techniques were utilized to see the interaction of GCV with excipients such as lactose, microcrystalline cellulose (MCC), magnesium stearate, and talc, and dicalcium phosphate. Further, a molecular docking study was also done to know the interaction of GCV with excipients. In vitro study of a physical mixture of GCV with excipients was performed to get the release of drug. Material and Methods: A number of analytical techniques (differential scanning calorimetry [DSC] using DSC-Q20, TA instruments, Fourier-transform infrared spectroscopy [FTIR] spectroscopy using Spectrum RX 1, nuclear magnetic resonance [NMR] using Bruker Advance Neo 500 MHz NMR spectrometer, etc.) have been used to explore the drug-excipient compatibility. Further, a suspected interaction was evaluated by thin-layer chromatography (TLC). In vitro dissolution studies in different sets of experiments were accomplished to determine the influence of hydrophobic and hydrophilic attributes of excipients (MCC, lactose, dicalcium phosphate, and talc) on the dissolution profile of GCV using USP1-type dissolution apparatus. Furthermore, in silico molecular docking studies were also performed to evaluate any probable molecular interactions among drugs and excipients using Auto Dock VINA 1.2.0 software and GROMACS 5.0 software. Results: Comparing FTIR and 1H NMR spectra of GCV and physical mixtures of GCV and excipients, no significant deviation of characteristic peaks in infrared spectroscopy and 1H NMR signals was observed. The DSC of GCV showed two sharp endothermic peaks at 238.82°C and 255°C. The endothermic peak of GCV in DSC thermogram of physical mixtures was observed in nearly the same position except with lactose and dicalcium phosphate. A slightly deviated peak of GCV with a physical mixture of drug and lactose and dicalcium phosphate indicated that there were suspected interactions between the drug with lactose and dicalcium phosphate. These interactions were evaluated by thin-layer chromatography (TLC) and it confirmed that there was no interaction between drugs and excipients. In vitro dissolution studies determined the influence of hydrophobic and hydrophilic attributes of excipients on the dissolution profile of GCV. The physical mixture of GCV with MCC displayed a maximum amount (66.48%) of drug release in 10 min. On the other hand, a physical mixture of GCV with talc showed a minimum amount (12.08%) of drug release in 10 min. Docking study predicted that the number of interactions were more between GCV and lactose (four nos.) in comparison to GCV and MCC (two nos.). This interaction supported the in vitro drug release of a physical mixture of GCV with MCC which was higher than a mixture of GCV with lactose. Conclusion: Compatibility testing of GCV with used excipients by analytical techniques confirmed that GCV should be compatible with used excipients. Drug dissolution of GCV and physical mixture of MCC exhibited the maximum amount of drug release whereas a mixture of GCV with talc released the minimum amount of drug for both short (10 min.) and long (60 min.) periods. Docking studies disclosed that the lactose complex showed less deviation with less root mean square deviation value in comparison to the microcrystalline complex. Thus, the lactose complex has more hydrogen bonds and it was more stable as compared with the MCC complex. GCV indicates that the total energy of the MCC complex is less than that of the lactose complex. This indicates that GCV is more soluble when combined with the microcrystalline complex. Therefore, GCV and used excipients could be used for solid dosage formulations.

Repurposing of monacolin K decorated BN nanoparticle on inhibition of HMG-CoA reductase: In silico approach

To identify a novel inhibitor of 3‑hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the current perspective has shifted toward a B12N12 nanocage that also has cardioprotective properties. Therefore, this study identified the bioactive complexes derived from monacolin K and BN nanoparticle and determines their potential for inhibiting HMG-CoA reductase, hypolipidemic activity, and anti-apoptotic properties via molecular docking. A molecular docking study was conducted with the Auto Dock Vina software on a complex of monacolin K and the B12N12 fullerene using an in silico docking approach. The protein structures of selective HMG-COA reductase, as well as peroxisome proliferator-activated receptor-α (PPAR-α) and others, were obtained from Protein Data Bank (PDB). The binding affinity between key residues involved in the binding mode of the targets and selective complexes is identified via in silico molecular docking. A further evaluation of the ADMET properties of the selective complexes has also been carried out. B12N12 nanoparticles and monacolin K complex (A) showed higher inhibitory potential for HMG-CoA reductase than monacolin K alone. These complexes seemed to be selective to the PPAR-α and caspase3 domains. Meanwhile, complex B had the highest binding affinity to the active site of SGK, TNF- α, NF-Kβ and AMPK receptors. Furthermore, both complex A and B could inhibit inflammatory targets more efficiently. The selective B12N12 nanoparticles were assessed for their drug-likeness and ADMET analysis, confirming that the selective B12N12 nanoparticles met the Lipinski and drug-likeness criteria. It was revealed that B12N12 fullerene and monacolin K complexes have potential inhibitory HMG-COA reductase and anti-apoptotic properties, as well as activating PPAR-α and AMPK. Consequently, these cardioprotective effects lead to improved cardiovascular health.

Network pharmacology and molecular docking study on the treatment of polycystic ovary syndrome with angelica sinensis- radix rehmanniae drug pair.

This study aimed to investigate the angelica sinensis - radix rehmanniae (AR) role in polycystic ovary syndrome (PCOS), employing network pharmacology and molecular docking techniques for active ingredient, targets, and pathway prediction. AR active components were obtained through TCMSP platform and literature search. The related targets of AR and PCOS were obtained through the disease and Swiss Target Prediction databases. An "active ingredient-target" network map was constructed using Cytoscape software, and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis was conducted through Hiplot. Finally, Auto Dock Tools software was used to conduct molecular docking between active ingredients and core targets. The main bioactive ingredients of AR in the treatment of PCOS are acteoside, baicalin, caffeic acid, cistanoside F, geniposide, etc. These ingredients involve 10 core targets, such as SRC, HSP90AA1, STAT3, MAPK1, and JUN. The effect of AR on anti-PCOS mainly involves the AGE-RAGE signaling pathway, Relaxin signaling pathway, TNF signaling pathway, and ErbB signaling pathway. Molecular docking results showed that the main active components and key targets of AR could be stably combined. AR can improve hyperandrogen status, regulate glucose homeostasis, and correct lipid metabolism and other physiological processes through multi-component, multi-target, and multi-pathway. Thus, it could play a significant role in PCOS treatment. The results of our study provide a scientific foundation for basic research and clinical applications of AR for the treatment of PCOS.

Potential energy surface, effect of solvents in molecular level, experimental spectra (FTIR, Raman, UV–visible & NMR), electronic, and dynamics simulation of isobavachalcone –Anti tuberculosis agent

The spectroscopic characteristics, molecular structure, and biological characteristics of the Isobavachalcone (IBC) structure have been studied using computational techniques utilizing the usual B3LYP/6-311++G (d,p). PED (Potential Energy Distribution) is used throughout process of assigning the fundamental wave-numbers of IBC. In this work, we have reported the correlation between experimental and computed examination of molecular configuration, FT:IR & Raman, UV–Visible absorption, and NMR (Nuclear Magnetic Resonance) spectrum of the title compound. Potential energy scan (PES) analysis of IBC was enhanced in the initial stage with same basis set. FMO (Frontier Molecular Orbital), MEP (Molecular Electrostatic Potential), local reactivity and quantum chemical descriptors has also been analyzed. Furthermore, drug-likeness and ADMET predictions of the present ligand shows good pharmacological activity. ELF (Electron Localised Function), LOL (Localised Orbital Locator) and RDG (Reduced Density Function) enacted for both the gas and solvents phases. A docking simulation performed with the 2FUM receptor using the Auto Dock software showed that the IBC compound has inhibitory activity against Mycobacterium tuberculosis disease. All our results suggest that the IBC molecule could have a great effect in the treatment of tuberculosis disease. MD simulations been executed over 100 ns to predict the RMSD, RMSF, and the radius-of gyration analyses.

Identification of biomarkers of acne based on transcriptome analysis and combined with network pharmacology to explore the therapeutic mechanism of Jinhuang ointment.

The incidence of acne is on the rise due to unhealthy diet and living habits. Jinhuang ointment (JHO) is a classic prescription composed of 10 kinds of commonly used Chinese herbal medicine, which has been widely used in clinical prevention and treatment of skin inflammatory diseases since ancient times. However, the pharmacological mechanism and target of JHO are not clear. The acne microarray dataset was downloaded from gene expression omnibus database to identify differentially expressed genes (DEG). Immune infiltration was analyzed by CiberSort algorithm. HUB gene was identified by protein-protein interaction network. The gene expression omnibus dataset validates the biomarkers of acne with high diagnostic value. The potential active components and targets of JHO were obtained through Traditional Chinese Medicine Systems Pharmacology database, and the therapeutic targets were obtained by crossing with disease targets. R-packet is used for enrichment analysis. Molecular docking using Auto Dock Tools. A total of 202 DEGs were identified from 12 skin samples in the GSE6475. Immune infiltration analysis showed that there were a large number of macrophages and mast cells in acne skin. Gene set enrichment analysis analysis showed that DEGS was mainly involved in bacterial reaction, inflammatory reaction and so on. Six central genes and gene cluster modules were identified by Cytoscape software. A total of 185 JHO active components and 220 targets were obtained, of which 10 targets were potential targets for JHO in the treatment of acne. Kyoto encyclopedia of genes and genomes enrichment analysis showed that JHO treatment of acne was mainly related to Toll-like receptors, IL-17 and other signal pathways. The results of molecular docking showed that 5 active compounds in JHO had strong binding activity to the core protein receptor. IL-1 β, CXCL8, toll-like receptor 2, CXCL2, LCN2, and secretory phosphoprotein 1 may be potential biomarkers for early diagnosis of acne. JHO active components may regulate skin cell metabolism and inflammatory response and improve cellular immune microenvironment by acting on core targets (CXCL8, ESR1, IL-1 β, MMP1, MMP3, secretory phosphoprotein 1), thus achieving the purpose of treating acne. This is the result of the joint action of multiple targets and multiple pathways. It provides an idea for the development of a new combination of drugs for the treatment of acne.

Network Pharmacology-Based Prediction of Active Ingredient and Mechanisms of Astragalus membranaceus and Panax notoginseng Coupled- Herbs Against Diabetic Neuropathic Pain

Background: Diabetic neuropathic pain seriously affects the quality of a patient’s life. To predict molecular mechanism based on network pharmacology and verify the interaction between the active ingredient of Astragalus membranaceus and Panax notoginseng coupled-herbs (AP) and target genes related to Diabetic neuropathic pain (DNP) molecular docking assay was performed. AP and their target genes related to DNP were analyzed based on network pharmacology followed by experimental validation. Methods: TCMSP, PubMed and CNKI websites were used to acquire active components in AP. OMIM, DrugBank database and DisGeNET database were used to collect and analyze target genes related to DNP. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) analysis were conducted in the DAVID database. The protein-protein interaction (PPI) network model was constructed by introducing the selected components-disease common target into the string database. Auto- Dock Vina 1.1.2 was used to dock receptor proteins with small ligand molecules. VonFrey’s statement was used to detect mechanical allodynia of DNP rats. Potential targets were detected by Western blot assay. Results: We decided that 22 and 9 chemical compositions possessed the fair ability of absorption, distribution, metabolism and excretion in Astragalus membranaceus and Panax notoginseng, respectively. These active compositions act on 70 target genes related to DNP. The core gene in the protein-protein interaction network are CAT, ESR1, HMOX1, IL1β, IL6, NFE2L2, NOS2, PPARG, PTGS2 and TNF, etc. Furthermore, GO, and KEGG pathway enrichment analyses indicated that DNP related target genes regulated by AP exist in multiple signaling pathways, including insulin resistance, PI3K-Akt signaling, HIF-1 signaling pathway, Fluid shear stress and atherosclerosis, and AGE-RAGE signaling pathway etc. AP inhibited mechanical hyperalgesia and reduced SERPINE1, FN1, IL1β, and IL6 expression of diabetic neuropathic rats in a dose-dependent manner. Conclusion: We first confirm that AP possess an anti-DNP effect through multiple signaling pathways based on network pharmacology. These results provide a theoretical basis for us to further research on the molecular mechanism of AP in the treatment of DNP.

Isolation and Characterization of Chemical Compounds from Terminalia Chebula for Anti-Diabetic Evaluation Through In-Silico Approach

Diabetes is a chronic metabolic disorder affecting millions of people and needs to be addressed. Alternativestrategies are required for better diabetes management, as evidenced by the high costs of modern medicines. The field of herbalmedicine research has been gaining significant importance in the last few decades, and the demand to use natural products in thetreatment of diabetes is increasing across the globe. Traditional plant medicines are used worldwide for a range of diabeticcomplications. Terminalia chebula is one of the widely used traditional medicine by diabetic patients. In this present work,Terminalia chebula fruits were used for the potential of anti-diabetic activity. The phytochemical investigation revealed that itsfruit contains high amounts of tannins, alkaloids, flavonoids, terpenoids, and glycosides. The percolation method was followed byusing T. chebula fruit for the extraction, further fractionating with different solvents, n-Hexane, Ethyl acetate, n- Butanol, andwater. When ethyl acetate extract of T. chebula was tested, it was found to have significant effects on blood glucose levels. Itsuggests that it can be used as an antidiabetic agent. Gallic acid and quercetin were compounds identified by NMR, MS, andUPLC analysis. Molecular docking studies of designed compounds were carried out through Auto Dock Vina [1.1.2] toinvestigate the interaction with PPAR-γ associated with diabetes, and pkCSM software was used for ADMET analysis. Thus, theresult of the study proved that the ethyl acetate extract of T. chebula had good potential as an antidiabetic, and this plant can beused to discover natural bioactive compounds that may serve for the advances of novel pharmaceutical development. Moreover,the compounds found in the extract could be used to develop new pharmaceuticals for diabetes treatment.

Tannin derived from Uncaria gambir Roxb. as potential Enterococcus faecalis UDP-N-Acetylenolpyruvoyl-Glucosamine Reductase (Mur Benzyme) inhibitor: In-silico antibacterial study

The high prevalence of pulp and periapical disease is an important problem for dental and oral health in dentistry. Treatment of pulp and periapical disease is generally carried out utilizing root canal treatment, but the results of the treatment are often not as expected. Enterococcus faecalis is a bacterium that plays a role in the failure of root canal treatment. E. faecalis are Gram-positive bacteria that use the Muramidase B (MurB) enzyme in the biosynthesis of peptidoglycan, which will build bacteria cell walls and play an important role in protecting bacteria. Gambir (Uncaria gambir Roxb.) is an herbal plant that is used in the field of medicine and contains tannin compounds that have antibacterial activity. The purpose of this study was to predict the antibacterial activity of Gambir extracts against the MurB enzyme compared with chlorhexidine through in silico approach. The Mur B enzyme was obtained from the Protein Data Bank (PDB), and the structure of the compound (tannins and chlorhexidine) was obtained from Pubchem. Using Auto dock tools from Pyrx software for docking between the two compounds (tannin and chlorhexidine) with the MurB enzyme, and visualize using Pymol and 3D analysis using Biovia. The results showed that tannins had a binding affinity of more than -7.4 kcal.mol-1 to the MurB enzyme and chlorhexidine had a higher binding affinity than tannins. Both tannins and chlorhexidine have hydrogen bonds with the same three amino acids, that is ARG 159, GLY 123, and ASN 233. The results showed that tannins interacted with the MurB enzyme and could inhibit the action of the MurB enzyme.

In silico analysis of RPS4X (X-linked ribosomal protein) with active components from black seed (Nigella sativa) for potential treatment of multiple sclerosis

Multiple sclerosis is a complex disorder that is caused by demyelination and loss of axonal parts in the central nervous system. It is caused by many environmental and genetic factors. Various genetic markers such as HLA-DRB1, myelin basic protein, oligodendrocytic glycoprotein, caspase 1, interleukin-1, CD-20, Gap-43 protein, RPS4X (X-linked ribosomal protein), and fibrinogen are some of the factors involved in multiple sclerosis. The ribosomal protein S4 is upregulated in the MS brain. This disease is treated with several synthetic medicines and stem cell therapies which are associated with various side effects. Nigella sativa possesses neuroprotective, antioxidant, and anti-inflammatory properties with no potential side effects which make this plant a potential candidate for the treatment of multiple sclerosis in animal models as well as humans. However, its implications in MS are mainly limited to thymoquinone application. Thus, the present study is an attempt to investigate the role of bioactive molecules other than thymoquinone. Using Auto Dock vina, we investigated the interaction between the RPS4X gene protein of both quail and mouse with the herbal components. Although thymoquinone is the main active component of this herb, it was excluded due to its higher binding energy (-5.0 kcal/mol mouse, -5.3 kcal/mol quail) for the RPS4X gene. Out of 56 components quercetin (-7.0 kcal/mol mouse, -6.9 kcal/mol quail), and kaempferol (-6.7 kcal/mol mouse, -6.5 quail) were identified as the most potent components antioxidant based on their affinity values. Both of them have low toxicity and based on Density Functional Theory (DFT) Calculation kaempferol was the more reactive while quercetin was more stable. The molecular dynamic simulations showed stable binding interaction and flexibility of docked complexes confirming kaempferol and quercetin as potential binders for the proteins. Our data support the interaction between gene and active components of Nigella sativa and suggest their potential involvement in multiple sclerosis treatment.

In-Silico Validation of Niazinin-A Against Proinflammatory Mediator: Anti-Proliferative Potential

Background: Cancer is one of the most dreaded human diseases, that has become an ever-increasing health problem and is a prime cause of death globally. Munga, also known as Moringa oleifera Lam., is one of the most significant plants grown extensively in India. This plant, Moringa oleifera Lam, is used extensively as a dietary supplement and has valuable pharmacological properties including anti-asthmatic, anti-diabetic, hepatoprotective, anti-inflammatory, anti-cancer, antimicrobial, anti-oxidant, cardiovascular, anti-ulcer, CNS activity, anti-allergic, wound healing, analgesic, and antipyretic action. This plant has great therapeutic properties in every area. It is a good source of milk protein, vitamin A, and vitamin C. Alkaloids, protein, quinine, saponins, flavonoids, tannin, steroids, glycosides, fixed oil, and lipids are only a few examples of the several active phytoconstituents that are present. Aim: The current work sought to elucidate the molecular basis for Niazinin A antiproliferative activity against the VEGF-1 &amp; AURKA, which functions as a proinflammatory factor in proliferation. Method: A molecular docking method was employed in the current work to look for VEGFR-1 &amp; AURKA protein inhibitors. The binding was determined by the Auto Dock software utilising a grid-based docking method. Results: The molecular docking result revealed that Niazinin A showed encouraging docking score. The docking score found to be -7&amp; -6.11 for VEGF-1 &amp; AURKA kcal mol–1 respectively. Conclusion: The interaction of ligand hits to targeted site and docking score finding it can be predicted that Niazinin A found in the plants Moringa exhibited good inhibitor of VEGF-1 &amp; AURKA protein.

Human Centromere associated protein (CENP-A, B, S, N, E) binding potentials of Nitrile compounds: An in silico study

In the present investigation, different nitrile compounds synthesized earlier using one pot synthesis method were studied for Human Centromere Protein (CENP’s) binding potentials in silico so as to treat different types of cancers. An advanced auto dock 4.2 version was used for the study. Among 12 nitrile compounds studied, compound 2 (4-chloro,3cyano cumarin) and compound 11 (2-nitrile chromone) exhibited highest binding affinity to CENP-A,B,S and E proteins while rest of the nitrile compounds under study showed moderate degree of binding to CENP’s. Among 4.0 proteins studied, highest biding affinity of the compound 2 and 11 was recorded with protein A followed by B and E while least binding of the nitrile compounds was found to the protein S. Hence, from the above results viz. binding scores, hydrogen bond, Van der waals interactions of the nitrile compounds with the CENP’s, it can be concluded that the compounds 2 and 11 have the potential to develop as drugs for treating cancers targeting CENP proteins. However, further in vitro and in vivo investigations are required to develop as final drug.