Interaction Of Active Compounds Research Articles

Exploring the anti-inflammatory and immunomodulatory potential of licochalcone B against psoralidin-induced liver injury

Ethnopharmacological relevanceHerb-induced liver injury (HILI) represents an exacerbated inflammatory response, with Psoraleae fructus (PF) and its preparations recently associated with hepatotoxicity. Licorice, historically recognized as a detoxifying herbal remedy, is considered to possess hepatoprotective properties. Our previous research identified bavachin, bakuchiol, and psoralidin (PSO) as potential toxic constituents in PF, while licochalcone B (LCB) and echinatin were identified as bioactive components in licorice. However, evidence regarding the interactions of active compounds in herbs and their underlying mechanisms remains limited. Aim of the studyThe objective of this study is to assess the potential mechanisms through which LCB modulates immunological and anti-inflammatory responses to treat PSO-induced liver injury by using human hepatocyte cells (L02) and LPS-primed mice. MethodsThe ameliorative effects of LCB and echinatin on bavachin, bakuchiol, and PSO-induced liver injury were demonstrated in L02 cells. Subsequently, the efficacy of LCB on PSO-induced idiosyncratic liver injury was further validated in C57BL/6 mice under moderate inflammatory stress induced by LPS priming. The mechanisms were preliminarily explored with an integrated strategy of molecular docking, RT-PCR verification, and untargeted metabolomics. ResultsThe study shows that LCB significantly reduced cell injury induced by the three chemicals in PF and provided substantial protection against PSO-induced hepatic damage, as indicated by the levels of ALT, AST, and LDH. LCB normalized liver function and remarkedly alleviated hepatic lesions and inflammation caused by PSO in mice under moderate inflammatory stress. The mRNA profiles of both L02 cells and mice liver tissue revealed that LCB mitigated PSO-induced hepatotoxicity by regulating the gene expression of pro-inflammatory cytokines IL1B and TNF, as well as immunoinflammatory genes PIK3CA, AKT1, NFKB1, and NLRP3. Furthermore, untargeted metabolomics of liver tissue indicated that LCB could reverse the abnormal expression of 11 discriminatory metabolites, with the interrelationship between differential metabolites and target genes primarily clustering in glycerophospholipid metabolism, arachidonic acid metabolism, and phosphatidylinositol signaling system. ConclusionLCB demonstrated a superior anti-inflammatory and immunomodulatory effect on PSO-induced hepatotoxicity by modulating the inflammatory response and metabolic signaling system. Key interactive targets included phosphatidylcholine, phosphatidic acid, and subunit isoforms of PI3K.

Direct Oral FXa Inhibitors Binding to Human Serum Albumin: Spectroscopic, Calorimetric, and Computational Studies.

Direct FXa inhibitors are an important class of bioactive molecules (rivaroxaban, apixaban, edoxaban, and betrixaban) applied for thromboprophylaxis in diverse cardiovascular pathologies. The interaction of active compounds with human serum albumin (HSA), the most abundant protein in blood plasma, is a key research area and provides crucial information about drugs' pharmacokinetics and pharmacodynamic properties. This research focuses on the study of the interactions between HSA and four commercially available direct oral FXa inhibitors, applying methodologies including steady-state and time-resolved fluorescence, isothermal titration calorimetry (ITC), and molecular dynamics. The HSA complexation of FXa inhibitors was found to occur via static quenching, and the complex formation in the ground states affects the fluorescence of HSA, with a moderate binding constant of 104 M-1. However, the ITC studies reported significantly different binding constants (103 M-1) compared with the results obtained through spectrophotometric methods. The suspected binding mode is supported by molecular dynamics simulations, where the predominant interactions were hydrogen bonds and hydrophobic interactions (mainly π-π stacking interactions between the phenyl ring of FXa inhibitors and the indole moiety of Trp214). Finally, the possible implications of the obtained results regarding pathologies such as hypoalbuminemia are briefly discussed.

Dual-target affinity analysis and separation of α-amylase and α-glucosidase inhibitor from Morus alba leaves by magnetic bifunctional immobilized enzyme system.

Morus alba leaves is a natural product with great anti-diabetic potential. However, the therapeutic efficacy of natural product is usually achieved through the interaction of active compounds with specific targets. Among them, active compounds with multi-target therapeutic functions are more effective than single target enzyme. In this study, a bienzyme system was constructed by co-immobilizing α-amylase and α-glucosidase onto Fe3 O4 for affinity screening of dual-target active component in the complex extract from M. alba leaves. As a result, a potential active compound was selectively screened by ligand fishing, separated by HSCCC using a solvent system of ethyl acetate-n-butanol-water (3:2:5, v/v), and identified as rutin. In addition, the result of molecular docking showed that rutin could interact with the active center of α-amylase and α-glucosidase through multiple hydrogen bonds, van der Waals forces, etc. to play an inhibitory role. These results demonstrated the effectiveness of polydopamine magnetically immobilized bienzyme system for dual-target affinity screening of active substance. This study not only revealed the chemical basis of the antidiabetic activity of M. alba leaves from a dual-target perspective, but also promoted the progress of multi-target affinity screening.

Identification Pharmacodynamic Interactions of Active Compounds of Diabetes Mellitus Type 2 Herbal Plants Using the Random Forest Method

Drug-drug interactions is defined as the modification of the effect of a drug as a result of another drug given simultaneously or with an interval or when two or more drugs interact so that the effectiveness or toxicity of one or more drugs changes. Pharmacodynamic interactions are one type of interaction that needs special attention because these interactions work directly on the body's physiological systems and compete on the same receptors so that they can be antagonistic, additive, or synergistic. The use of medicinal plants is becoming an alternative because in addition to their relatively safer side effects, medicinal plants consisting of active compounds are appropriate in treating degenerative metabolic diseases triggered by mutations in many genes. As in the case of polypharmacies, interactions of active compounds in medicinal plants can also lead to phapharmodynamic interactions. Therefore, it is also necessary to identify the active compounds so that it can then be known whether the interaction of the compounds will be beneficial or detrimental. In this study, pharmacodynamic identification was applied to Diabetes Mellitus Type 2 medicinal plant compounds by using the independent variables Target Protein Connectedness (TPC), Side Effect Similarity (SES), and Chemical Similarities (CS) using Random Forest classification method. From a search of various databases, 21 active compounds were obtained and then only 100 compound interactions could be calculated as independent variables. With an accuracy value and AUC of 0,96, there were 93 pairs of compounds that interacted pharmacodynamically and the remaining 7 did not interact.

Profil Metabolit Daun Kesambi (Schleichera oleosa) Berdasarkan Analisis Histokimia dan In Silico

Kesambi (Schleichera oleosa) is a plant belonging to the Sapindaceae familia. This study aims to determine the secondary metabolite compounds found in kesambi leaves through histochemical analysis and derivatives of active compounds in silico. Descriptive experimental research method was conducted in January using samples of kesambi plants that grow on the island of Madura. Histochemical analysis was carried out by preparing fresh leaves through lower leaf incisions with secondary metabolite detection reagents (CuSO4, FeCl3, Wagner, Sudan III, AlCl3 & FeCl3+NaCO3) then microscopic color changes were observed. In silico testing aims to determine the interaction of active compounds with ER? as a target for ER + breast cancer therapy through molecular docking. Supporting software used is KNApSAcK, Pubchem, Pass Online, PDB ID, PyRx, PyMol and Chimera 1.14. The results showed that through histochemical analysis six secondary metabolite compounds were identified, namely terpenoids, flavonoids, alkaloids, tannins, lipophils and phenols. While in silico analysis, the active compound is scopoletin which is derived from phenol, beta-sitosterol, betulin, betulinic acid, lupeol, lupeol acetate, schleicheol 1&2, schleicherastatin 1-7 which are derivatives of terpenoids. Based on the results of molecular docking, there are interactions of active compounds with 3ERT protein, the compounds that provide the most effective results as candidates for breast cancer drugs are lupeol acetate with a value of Root Mean Square Deviation (RMSD) lb 1,588 Å and ub 2,219 Å . Lupeol acetate compound is predicted to have activity as an Er? inhibitor against ER+ breast cancer.
 Keywords: Kesambi (Schleichera oleosa), histochemistry, molecular docking and ER?.

Inhibition Profiling of Urease and Carbonic Anhydrase II by High- Throughput Screening and Molecular Docking Studies of Structurally Diverse Organic Compounds

Background:: Structurally diverse organic compounds and available drugs were screened against urease and carbonic anhydrase II in a formulation acceptable for high-throughput screening. Objective: The study was conducted to find out potential inhibitors of urease and carbonic anhydrase II. Methods:: Quantification of the possible HITs was carried out by determining their IC50 values. Results: The results of several screened compounds, including derivatives of oxadiazole, coumarins, chromane-2, 4-diones and metal complexes of cysteine-omeprazole showed promising inhibitory activities with IC50 ranging from 47 μM to 412 μM against the urease. The interactions of active compounds with active sites of enzymes were investigated through molecular docking studies which revealed that (R)-1-(4-amino-4-(5-(thiophen-2-yl)-1,3,4-oxadiazol-2-yl) butyl) guanidine possessing IC50 of 47 μM interacts with one of the nickel metal atoms of urease besides further interactions as predictable hydrogen bonds with KCX490, Asp633, His492, His407 and His409 along with Ala440 and 636. Bi-ligand metal complexes of 4-aminoantipyrine based Schiff bases showed activation of urease with AC50 ranging from 68 μM to 112 μM. Almost 21 compounds with varying functional groups including pyrimidines, oxadiazoles, imidazoles, hydrazides and tin based compounds were active carbonic anhydrase II inhibitors presenting 98 μM to 390 μM IC50 values. Several N-substituted sulfonamide derivatives were inactive against carbonic anhydrase II. Conclusion:: Among all the screened compounds, the highly active inhibitor of carbonic anhydrase II was (4-(3-hydroxyphenyl)-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl) methanone with IC50 of 98.0 μM. This particular compound showed metallic interaction with Zn ion of carbonic anhydrase II through the hydroxyl group of the phenyl ring.

An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma.

Aims. Abundant evidences in traditional Chinese medicine (TCM) supported the therapeutic value of herbal medicine Yinchen in hepatocellular carcinoma (HCC), but the underlying mechanism remains to be investigated. Main Methods. The intersection of immune gene set, module genes, HCC-associated genes, and target genes of Yinchen was employed for further analyses. The module genes were identified by weighted gene coexpression network analysis, and the other three gene sets were obtained from public databases. Subsequently, we further explored the clinical value and immunoregulation of the hub gene of intersection. The relevant pathways related to hub gene expression were investigated by gene set enrichment analysis. Finally, the interaction of active compounds and target genes was validated by molecular docking. Key Findings. Thirteen active compounds and 90 target genes of Yinchen were included. After constructing the network among Yinchen, target genes, and HCC, BIRC5 was identified as the hub gene. Significant difference was found between the high-expressed group and the low-expressed group in survival and stage. Different immune subtypes also presented significant difference in BIRC5 expression. Moreover, NK cell and T cell (CD4+ effector memory and CD4+ memory resting) were negatively correlated with BIRC5 expression, while CTLA4 and LAG3 were positively correlated. The results of molecular docking further validated a good binding activity of quercetin-BIRC5 interaction. Significance. In summary, our research identified for the first time a novel underlying association among herbal medicine Yinchen, BIRC5, immunotherapy, and HCC. We speculated that Yinchen may target the immune checkpoints (CTLA4 and LAG3) and activate the immune cells by suppressing BIRC5.

Molecular dynamics and bio-synthesis of phoenix dactylifera mediated Mn3O4 nanoparticles: Electrochemical application

The study reports computational and experimental synthesis of Mn3O4 nanoparticles using extracts of Phoenix dactylifera otherwise known as date pits for electrochemical applications. The interaction of active compounds which are Gallic acid, L-Glutamic acid, and Sinapic acid contained in date pits serving as reducing agents with the Mn3O4 nanoparticle is investigated using molecular dynamics (MD). The MD analysis enabled to guess the behaviour of the active compounds with the Mn3O4 nanoparticles. Analysis of the density maps and Radial Distribution Function (RDF) showed that, L-Glutamic acid has the most hydrophilicity and the less affinity to interact with the Mn3O4 nanoparticle compare to Gallic and Sinapic acids. By experimental analysis via UV-Vis absorbance, the presence of the active compounds is confirmed at absorbance peaks of 280 and 330 nm. Subsequently, the aqueous extracts obtained from date pits are used to bio-synthesized Mn3O4 nanoparticles.Un-annealed Mn3O4 nanoparticles are thermally oxidized in air for 2 h at 500 °C and 700 °C and subsequently characterized using Diffuse reflectance, XRD, FTIR, HRTEM, HRSEM, and EDS. As direct application, electrochemical properties of Mn3O4 nanoparticles are evaluated using Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS).XRD analysis revealed plenty of diffraction peaks which are harmonized to Hausmannite Mn3O4 phase. Meanwhile the crystallinity of samples with increasing annealing temperature was evaluated from SAED images characterized by the presence of scattered bright diffractions spots. The electrochemical analysis exhibited an excellent voltammetry response and good electrochemical performance making Hausmannite Mn3O4 nanoplatelets a promising material for electrochemical applications.

Synthesis, Anti-inflammatory Activity and in silico Studies of Some Novel Morpholine Based Carboxamides

Two series of carboxamides were synthesized from 3-fluoro-4-morpholinoaniline and different substituted aromatic/heterocyclic carboxylic acids. All the compounds were characterized by IR, 1H NMR, 13C NMR and mass spectral data. The newly synthesized amide derivatives were screened for anti-inflammatory activity by following carrageenan induced rat paw edema method. Among the compounds screened, compound 6e was found to be highly potent. Molecular docking interaction of active compounds revealed that effective binding was observed in the pocket of COX-I and COX-II proteins.

Interaction of active compounds from Aegle marmelos CORREA with histamine-1 receptor

The aim of this study is to determine the affinity of six active compounds of Aegle Marmelos Correa, they are (E, R)-Marmin, skimmianine, (S)-aegeline, aurapten, zeorin, and dustanin as antihistamines in histamine H1 receptor in comparison to cetirizin, diphenhydramine and chlorpheniramine as ligands comparison. Previously, in the in vitro study marmin obviously antagonized the histamine H1 receptor in a competitive manner. Methods: molecular docking to determine the interaction of ligand binding to its receptor. Lower docking score indicates more stable binding to that protein. Results: Marmin, skimmianine, aegeline, aurapten, zeorin, and dustanin were potential to develop as antihistamine agents, especially as histamine H1 receptor antagonists by interacting with amino acid residues, Asp107, Lys179, Lys191, Asn198, and Trp428 of histamine H1 receptor. Conclusions: Based on molecular docking, Amino acid residues involved in ligand protein interactions were Asp107, Lys179, Lys191, Asn198, and Trp428.

Synthesis and Anti-HBV Activity of Novel Dihydropyrimidine Analogs

Fourteen novel dihydropyrimidine analogs were synthesized from aromatic nitriles through ammonolysis, acetylation, catalytic hydrogenation and cyclization procedures. All the compounds were characterized by 1H NMR, MS and elemental analysis and the antiviral activity was tested in transfected HepG2.2.15 cells. The results show that some compounds had effective activity. The IC50 of compounds 5c and 5n were 0.87 and 0.67 μmol/L, respectively. The structure-activity relationship of 2-heteroaryl was discussed and the interaction of active compounds with capsid was studied by size exclusion chromatography.