Globally, lung cancer remains one of the leading causes of cancer-related mortality, warranting the exploration of novel and effective therapeutic approaches. Soy-fermented food products have long been associated with potential health benefits, including anticancer properties. There is still a lack of understanding of the active components of these drugs as well as their underlying mechanistic pathways responsible for their anti-lung cancer effects. In this study, we have undertaken an integrated approach combining network pharmacology and molecular docking to elucidate the mechanism of action of soy-fermented food products against lung cancer through simulation and in vitro validation. Using network pharmacology, we constructed a comprehensive network of interactions between the identified isoflavones in soy-fermented food products and lung cancer-associated targets. Molecular docking was performed to predict the binding affinities of these compounds with key lung cancer-related proteins. Additionally, molecular simulation was utilized to investigate the stability of the compound–target complexes over time, providing insights into their dynamic interactions. Our results identified daidzein as a potential active component in soy-fermented food products with high binding affinities towards critical lung cancer targets. Molecular dynamic simulations confirmed the stability of the daidzein–MMP9 and daidzein–HSP90AA1 complexes, suggesting their potential as effective inhibitors. Additionally, in vitro validation experiments demonstrated that treatment with daidzein significantly inhibited cancer cell proliferation and suppressed cancer cell migration and the invasion of A549 lung cancer cells. Consequently, the estrogen signaling pathway was recognized as the pathway modulated by daidzein against lung cancer. Overall, the findings of the present study highlight the therapeutic potential of soy-fermented food products in lung cancer treatment and provide valuable insights for the development of targeted therapies using the identified bioactive compounds. Further investigation and clinical studies are warranted to validate these findings and translate them into clinical applications for improved lung cancer management.

Background/Objectives: This study presents a novel and comprehensive investigation into the anti-colorectal cancer (CRC) effects and underlying mechanisms of Eruca sativa (E. sativa) using an integrated approach combining network pharmacology, molecular docking and molecular dynamics simulation. Methods: Using an integrated approach, six bioactive compounds and 40 potential targets were identified. A compound–target network was constructed, and enrichment analysis was performed to explore the key pathways influenced by E. sativa. Molecular docking analysis was used to evaluate the binding interactions between the identified compounds and key CRC-related targets (AKT1, PGR, MMP9, and PTGS2). Furthermore, molecular dynamics simulation was utilized to confirm the stability and reliability of these interactions. Results: The study found that E. sativa exhibits strong anticancer potential, particularly through major compounds such as β-ionone, 1-octanol, isorhamnetin, 2-hexenal, propionic acid, and quercetin. Molecular docking revealed favorable binding interactions between these compounds and key CRC targets, with quercetin and isorhamnetin showing the highest binding affinities. Additionally, molecular dynamics simulations validated the stability of these interactions, reinforcing their therapeutic relevance. Conclusions: This study provides valuable insights into the pharmacological mechanisms of E. sativa against CRC, highlighting its potential as a natural anticancer agent. These findings pave the way for future clinical studies to validate the efficacy and safety of E. sativa and its bioactive compounds, potentially contributing to the development of novel, plant-based therapeutic strategies for CRC treatment.

Breast cancer remains a significant global health challenge, necessitating the exploration of novel therapeutic options. The present study employs an integrated approach encompassing network pharmacology, molecular docking, molecular dynamics simulations, and in-vitro validation to investigate the potential of Selaginella bryopteris in breast cancer treatment. Initial network pharmacology analysis revealed different potential targets and pathways associated with breast cancer that could be modulated by S. bryopteris phytochemical constituents. Molecular docking and dynamics simulations further elucidated the stability and dynamics of protein-ligand complexes (lanaroflavone–EGFR and sequoiaflavone-CTNNB1). The in-vitro assays demonstrated the ability of S. bryopteris crude extract to inhibit cancer cell growth (IC₅₀ - 78.34 μg/mL) migration and invasion, supporting the computational predictions. The integrated approach employed in the present study offers a robust framework for the systematic exploration of S. bryopteris in drug discovery as a promising candidate for breast cancer treatment.

The present work set out to examine the antidiabetic capacity of Abelmoschus esculentus (okra) fruit extract through a combined experimental and computational framework. Enzyme inhibition assays were carried out against four metabolic targets, and IC₅₀ values stood at 7.66 ± 0.31 mg/mL for alpha-glucosidase, 5.21 ± 0.18 mg/mL for alpha-amylase, 2.11 ± 0.15 microg/mL for DPP-4, and 9.17 ± 0.54 mg/mL for pancreatic lipase. The extract showed moderate-to-weak activity relative to standard inhibitors acarbose, sitagliptin, and orlistat. Sixteen drug-like phytochemicals obtained from the IMPPAT 2.0 database were docked against the crystal structures of all four tested enzymes (PDB: 8CB1, 5E0F, 2ONC, 1LPB). Alpha-Carotene, Vitamin E, and Spiraeoside emerged as the top-ranked compounds across all targets, with alpha-Carotene recording the strongest binding affinity of −11.1 kcal/mol against pancreatic lipase, which was 4.2 kcal/mol more negative than the positive control orlistat (−6.9 kcal/mol). PLIP-based interaction profiling mapped out hydrogen bonds, hydrophobic contacts, pi-stacking, and salt bridges at the atomic level. Absorption, distribution, metabolism, and excretion (ADME) and toxicity screening of alpha-Carotene returned a favourable pharmacokinetic profile with predicted LD₅₀ of 1510 mg/kg (Class 4) and inactivity across most toxicity endpoints. A 100 ns molecular dynamics simulation of the pancreatic lipase-alpha–Carotene complex, alongside the orlistat control, showed stable root mean square deviation (RMSD) (0.15–0.22 nm), a consistent Rg (~1.97 nm), and sustained hydrogen bonding throughout the trajectory. Free-energy landscape analysis revealed a well-defined single energy basin for alpha-Carotene, suggesting a thermodynamically stable binding conformation. These findings lay the molecular basis for using okra phytochemicals as adjunctive agents in diabetes management, though in vivo validation remains necessary.

This study aims to investigate the potential anticancer effects of erucin, an isothiocyanate derived from Eruca sativa, in triple-negative breast cancer (TNBC) by predicting molecular targets and evaluating its in vitro effects on TNBC cell proliferation, apoptosis and cell cycle distribution. Potential protein targets of erucin were identified using SwissTargetPrediction, resulting in 117 targets, of which 84 overlapped with TNBC-related genes sourced from GeneCards, DisGeNET, and OMIM. Protein–protein interaction analysis was performed to identify key hub genes. In vitro experiments were conducted using MDA-MB-231 TNBC cells to assess dose-dependent effects on cell viability. Flow cytometry was employed to evaluate apoptotic cell populations and cell cycle distribution. Protein–protein interaction analysis identified ten hub genes, including AKT1, STAT3, EGFR, and MMP9, representing highly connected nodes within the predicted interaction network. In vitro studies showed dose-dependent reduction in MDA-MB-231 cell viability following erucin treatment, with an IC₅₀ of approximately 48.87 µg/mL. Flow cytometry revealed increased apoptotic cell population and G1 phase accumulation. These findings suggest that erucin is associated with cytotoxic and antiproliferative effects in TNBC cells and may interact with multiple cancer-related targets. However, the identified molecular targets and pathways are based on computational predictions and require further experimental validation. Overall, this study provides a preliminary integrated framework linking computational predictions with experimental observations, which may support future mechanistic and preclinical investigations of erucin in TNBC.