Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Analysis Reveal Insights into the Molecular Mechanism of Cordia myxa in the Treatment of Liver Cancer.

Traditional treatments of cancer have faced various challenges, including toxicity, medication resistance, and financial burdens. On the other hand, bioactive phytochemicals employed in complementary alternative medicine have recently gained interest due to their ability to control a wide range of molecular pathways while being less harmful. As a result, we used a network pharmacology approach to study the possible regulatory mechanisms of active constituents of Cordia myxa for the treatment of liver cancer (LC). Active constituents were retrieved from the IMPPAT database and the literature review, and their targets were retrieved from the STITCH and Swiss Target Prediction databases. LC-related targets were retrieved from expression datasets (GSE39791, GSE76427, GSE22058, GSE87630, and GSE112790) through gene expression omnibus (GEO). The DAVID Gene Ontology (GO) database was used to annotate target proteins, while the Kyoto Encyclopedia and Genome Database (KEGG) was used to analyze signaling pathway enrichment. STRING and Cytoscape were used to create protein-protein interaction networks (PPI), while the degree scoring algorithm of CytoHubba was used to identify hub genes. The GEPIA2 server was used for survival analysis, and PyRx was used for molecular docking analysis. Survival and network analysis revealed that five genes named heat shot protein 90 AA1 (HSP90AA1), estrogen receptor 1 (ESR1), cytochrome P450 3A4 (CYP3A4), cyclin-dependent kinase 1 (CDK1), and matrix metalloproteinase-9 (MMP9) are linked with the survival of LC patients. Finally, we conclude that four extremely active ingredients, namely cosmosiin, rosmarinic acid, quercetin, and rubinin influence the expression of HSP90AA1, which may serve as a potential therapeutic target for LC. These results were further validated by molecular dynamics simulation analysis, which predicted the complexes with highly stable dynamics. The residues of the targeted protein showed a highly stable nature except for the N-terminal domain without affecting the drug binding. An integrated network pharmacology and docking study demonstrated that C. myxa had a promising preventative effect on LC by working on cancer-related signaling pathways.

Biogenic zinc selenide nanoparticles fabricated using Rosmarinus officinalis leaf extract with potential biological activity.

Zinc selenide nanoparticles (ZnSe) are semiconductor metals of zinc and selenium. ZnSe NPs are advantageous for biomedical and bio-imaging applications due to their low toxicity. ZnSe NPs can be used as a therapeutic agent by synthesizing those using biologically safe methods. As a novel facet of these NPs, plant-based ZnSe NPs were fabricated from an aqueous extract of Rosmarinus officinalis L. (RO extract). Physiochemical analyses such as UV-visible and FTIR spectroscopy, SEM-EDX and TEM Imaging, XRD and DLS-Zeta potential analyses confirmed the biological fabrication of RO-ZnSe NPs. Additionally, Ro-ZnSe NPs were investigated for their bioactivity. There was an apparent peak in the UV-visible spectrum at 398 nm to confirm the presence of ZnSe NPs. FTIR analysis confirmed RO-extract participation in ZnSe NPs synthesis by identifying putative functional groups associated with biomolecules. TEM and SEM analyses revealed that RO-ZnSe NPs have spherical shapes in the range of 90-100 nm. According to XRD and EDX analysis, RO-ZnSe NPs had a crystallite size of 42.13 nm and contain Se and Zn (1:2 ratio). These NPs demonstrated approximately 90.6% antioxidant and antibacterial activity against a range of bacterial strains at 100 µg/ml. Antibiofilm activity was greatest against Candida glabrata and Pseudomonas aeruginosa at 100 g/ml. Accordingly, the IC50 values for anticancer activity against HTB-9, SW742, and HF cell lines were 14.16, 8.03, and 35.35 g/ml, respectively. In light of the multiple applications for ZnSe NPs, our research indicates they may be an excellent option for biological and therapeutic purposes in treating cancers and infections. Therefore, additional research is required to determine their efficacy.

Structural Dynamics of P-Rex1 Complexed with Natural Leads Establishes the Protein as an Attractive Target for Therapeutics to Suppress Cancer Metastasis.

Phosphatidylinositol 3,4,5-trisphosphate- (PIP3-) dependent Rac exchanger 1 (P-Rex1) functions as Rho guanine nucleotide exchange factor and is activated by synergistic activity of Gßγ and PIP3 of the heterotrimeric G protein. P-Rex1 activates Rac GTPases for regulating cell invasion and migration and promotes metastasis in several human cancers including breast, prostate, and skin cancer. The protein is a promising therapeutic target because of its multifunction roles in human cancers. Herein, the present study attempts to identify selective P-Rex1 natural inhibitors by targeting PIP3-binding pocket using large-size multiple natural molecule libraries. Each library was filtered subsequently in FAF-Drugs4 based on Lipinski's rule of five (RO5), toxicity, and filter pan assay interference compounds (PAINS). The output hits were virtually screened at the PIP3-binding pocket through PyRx AutoDock Vina and cross-checked by GOLD. The best binders at the PIP3-binding pocket were prioritized using a comparative analysis of the docking scores. Top-ranked two compounds with high GOLD fitness score (>80) and lowest AutoDock binding energy (< -12.7 kcal/mol) were complexed and deciphered for molecular dynamics along with control-P-Rex1 complex to validate compound binding conformation and disclosed binding interaction pattern. Both the systems were seen in good equilibrium, and along the simulation time, the compounds are in strong contact with the P-Rex1 PIP3-binding site. Hydrogen bonding analysis towards simulation end identified the formation of 16 and 22 short- and long-distance hydrogen bonds with different percent of occupancy to the PIP3 residues for compound I and compound 2, respectively. Radial distribution function (RDF) analysis of the key hydrogen bonds between the compound and the PIP3 residues demonstrated a strong affinity of the compounds to the mentioned PIP3 pocket. Additionally, MMGB/PBSA energies were performed that confirmed the dominance of Van der Waals energy in complex formation along with favorable contribution from hydrogen bonding. These findings were also cross-validated by a more robust WaterSwap binding energy predictor, and the results are in good agreement with a strong binding affinity of the compounds for the protein. Lastly, the key contribution of residues in interaction with the compounds was understood by binding free energy decomposition and alanine scanning methods. In short, the results of this study suggest that P-Rex1 is a good druggable target to suppress cancer metastasis; therefore, the screened druglike molecules of this study need in vitro and in vivo anti-P-Rex1 validation and may serve as potent leads to fight cancer.

Preparation of Zinc Oxide Nanoparticles Assisted by Okra Mucilage and Evaluation of its Biological Activities.

BACKGROUND: In this study, zinc oxide nanoparticles (ZnO-NPs) were biologically synthesized from Abelmoschus esculentus L. (Okra) mucilage fraction (OM). METHODS: Analytical techniques were employed to study the formation and properties of OM-ZnO NPs, including their morphology, shape, size distribution, and surface charges. Additionally, OM-ZnO NPs were assessed for their antimicrobial, antioxidant, and cytotoxic properties. RESULTS: UV-visible spectroscopy confirmed the formation of OM-ZnO NPs, evident by the appearance of an SPR peak at 368.8 nm. The FTIR spectroscopy demonstrated that OM functional groups contribute to the formation and stability of the NPs. Micrographs from TEM and SEM showed that OM-ZnO NPs ranged from 15-40 nm in diameter, whereas hydrodynamic diameter and surface charge values obtained from Zeta and DLS were 72.8 nm and 14.6 mv, respectively. XRD analysis indicated the OM-ZnO NPs were crystalline with a wurtzite structure and a crystallite size of 27.3 nm, while EDX revealed a zinc: oxygen ratio of 67.5:34. Further, the OM-ZnO NPs demonstrated significant antimicrobial activity in response to different types of bacteria. In the antioxidant assay, the OM-ZnO NPs scavenged DPPH with 68.6% of the efficiency of ascorbic acid (100%). CONCLUSION: The present study demonstrated the cytotoxic efficacy of MO-ZnO NPs against MCF7 cells with an IC50 of 43.99 µg/ml. Overall, the green synthesis of ZnO NPs by OM was successful for many biological applications, such as antimicrobial, antioxidant, and anticancer. Moreover, OM-ZnO NPs can be applied as a biologically-derived nanotherapeutic agent.