Unraveling the Antibacterial Mechanisms of Bletilla striata: A Synergistic Approach Combining Network Pharmacology, Molecular Docking, and In Vitro Validation.

In silico evaluation of novel metabolites from Tricholoma pardinum: Insights into drug-likeness, toxicity and target interactions via molecular docking and dynamics.

Six previously uncharacterized metabolites isolated from the poisonous mushroom Tricholoma pardinum are investigated using an integrated in silico approach to evaluate their therapeutic potential, highlighting the potential of metabolites from T. pardinum as novel scaffolds for developing anticancer agents targeting PARP1 and PIP4K2γ.

In-silico study of active phytochemicals and molecular mechanism of Hydrocotyle javanica Thunb.in treating MDR enterobacterial infection

It is highlighted that phytocompounds from Hydrocotyle javanica exhibit significant binding affinity toward key enterobacterial targets, along with favorable ADME and toxicity profiles, which suggest their potential as promising lead molecules for anti-enterobacterial drug development, warranting further experimental validation.

Elucidating the Therapeutic Mechanism of Puhuaiyin in Rosacea: An Integrated Study Based on Network Pharmacology, Bioinformatics, Molecular Docking, and Molecular Dynamics Simulations.

BACKGROUND Rosacea is a chronic inflammatory skin disorder with limited therapeutic options. Puhuaiyin (PHY), a traditional Chinese medicinal formula, shows clinical efficacy, but its multi-component mechanisms remain unclear. METHODS Chemical constituents of PHY were identified by UPLC-Q-TOF-MS. Network pharmacology was used to predict potential targets, which were intersected with rosacea-associated genes. Bioinformatics analyses (differential expression, WGCNA, and machine learning) were applied to the GEO dataset GSE65914 to refine core targets. Molecular docking and molecular dynamics simulations were conducted to validate the binding modes and stability between key active constituents and the core targets. RESULTS A total of 59 chemical constituents were identified in PHY, with five key active components subsequently screened: quercetin, emodin, kushenol N, physcion, and palmitic acid. Network pharmacology analysis revealed 44 intersecting targets, which were significantly enriched in inflammation-related pathways, such as MAPK, NF-κB, and JAK-STAT signaling. Integrated bioinformatics and machine learning approaches identified MMP9 and IL1B as core targets, both of which were markedly upregulated in rosacea lesions and demonstrated prominent diagnostic value (AUC = 0.999 for MMP9, 0.964 for IL1B). Molecular docking indicated strong binding affinity between the core components and MMP9/IL1B. Molecular dynamics simulations confirmed stable complex conformations over 200 ns, with MM/PBSA binding free energies of -15.54 Kcal/mol (quercetin-MMP9) and -15.57 Kcal/mol (quercetin- IL1B). DISCUSSION This study, through a multidisciplinary approach, systematically elucidates the "multi-component, multi-target, and multi-pathway" mode of action of PHY in the treatment of rosacea. However, the computational predictions remain to be further validated by in vivo and in vitro experiments. Future research should focus on verifying its therapeutic efficacy in animal or cellular models, as well as elucidating the regulatory effects of key active components on the MMP9 and IL1B targets. CONCLUSION These computational predictions suggest that PHY may exert therapeutic effects against rosacea via quercetin and other components targeting MMP9 and IL1B, thereby modulating MAPK, NF-κB, and JAK-STAT pathways. The proposed mechanisms include inhibition of inflammation, regulation of the immune microenvironment, attenuation of vascular dilation, and promotion of skin barrier recovery. These findings provide a theoretical basis for future experimental validation.

Computational Discovery of Phytochemicals Targeting InhA of Mycobacterium tuberculosis: Insights from Molecular Docking, MMGBSA, ADME Profiling, and Molecular Dynamics Simulations.

INTRODUCTION Tuberculosis (TB) is one of the most serious global health issues, with the increasing number of multidrug-resistant TB cases emphasizing the need for new therapeutic approaches. Phytochemicals, with their diverse structures and favorable safety profiles, are a largely unexplored area for anti-TB drug development. METHODS An ethnobotanical study and literature analysis identified 310 medicinal plants traditionally used to treat respiratory infections, which produced 4,087 phytochemicals. Their structures were obtained from PubChem or drawn using ChemDraw, and pharmacokinetic properties were analyzed using QikProp. Enoyl-acyl carrier protein reductase (InhA, PDB ID: 4TRO), an important enzyme involved in mycolic acid biosynthesis, was selected as the target protein. Molecular docking was performed using Glide, followed by MMGBSA calculations, and the best hits were validated by 300 ns molecular dynamics simulations using the GROMACS pipeline. RESULTS Binding affinities showed that four phytochemicals, namely Patuletin, skimmin, flavonol- 3-O-D-glycoside, and salicin, had significantly higher binding affinity scores (-10.06 to -8.82 kcal/mol) than first-line anti-TB drugs isoniazid (-6.35 kcal/mol) and pyrazinamide (-4.22 kcal/mol). Patuletin and skimmin had MM-GBSA binding affinity scores of -74.89 and -71.76 kcal/mol, respectively. MD simulations of the top 3 compounds and control showed that the protein-ligand complexes were stable, as indicated by the RMSD, RMSF, Radius of gyration, SASA, and HBONDS. DISCUSSION Patuletin and Skimmin demonstrated strong binding affinity and structural stability against the InhA enzyme (PDB: 4TRO), indicating their potential as promising lead compounds for anti-tuberculosis effects. Derived from ethnomedicinal plants, these phytochemicals not only target key mycobacterial pathways but may also offer hepatoprotective and immunomodulatory benefits. The findings support the exploration of plant-derived compounds as safer and effective alternatives or adjuncts to conventional anti-TB therapies. CONCLUSION The combination of virtual screening, ADME studies, and MD simulations enabled the identification of phytochemicals with promising interactions toward InhA, an established anti-TB target. The findings are based solely on computational analysis and should be interpreted as preliminary evidence of target engagement rather than confirmed inhibitory activity or therapeutic efficacy. These natural products may serve as potential lead compounds for further anti-tubercular drug discovery, warranting subsequent biochemical, cellular, and in vivo validation to establish their inhibitory potential, safety, and pharmacological effectiveness.

Metabolomics-guided network pharmacology and molecular modeling suggest bioactive components of Chiliadenus montanus associated with multi-target anticancer and anti-inflammatory activities

In Silico Pharmacological Evaluation and ADME Profiling of Berberine and Rosmarinic Acid as Potential Inhibitors of Escherichia Coli Dihydrofolate Reductase

Antimicrobial resistance has increased the need to identify alternative antibacterial scaffolds targeting established bacterial pathways. Dihydrofolate reductase (DHFR) is an established antimicrobial target involved in bacterial folate metabolism. This study evaluated selected natural compounds as potential inhibitors of Escherichia coli DHFR (ecDHFR) using molecular docking followed by in silico drug-likeness and pharmacokinetic profiling. Ten natural compounds were screened against ecDHFR using the CB-Dock platform, and their predicted binding scores were compared with the reference inhibitor trimethoprim. The two highest-ranked compounds were subsequently evaluated using SwissADME. Rosmarinic acid and berberine demonstrated the most favorable predicted docking scores, with Vina scores of −9.0 and −8.8 kcal/mol, respectively. Both compounds showed zero violations of Lipinski's rule of five. Rosmarinic acid demonstrated low predicted gastrointestinal absorption, whereas berberine showed high predicted gastrointestinal absorption and predicted inhibition of CYP2C9 and CYP3A4. These findings identify berberine and rosmarinic acid as natural-product scaffolds worthy of further investigation against ecDHFR. However, the computational findings do not establish direct enzyme inhibition or antibacterial efficacy. Experimental enzyme inhibition, antibacterial susceptibility, pharmacokinetic, and safety studies are required to validate these predictions.