Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and dysregulated chemokine signaling. Kaempferia parviflora (KP) has long been valued for its medicinal properties; however, its specific role in psoriasis treatment remains unclear. This study investigates the anti-psoriatic potential of methoxyflavones derived from KP through an integrated approach combining network pharmacology, molecular docking, and experimental validation. A total of 232 target genes were identified as being associated with KP bioactive compounds, of which 64 overlapped with psoriasis-related genes implicated in chemokine signaling pathways. Molecular docking analyses revealed that key methoxyflavones interact with pivotal proteins such as protein kinase B (AKT1 or AKT), proto-oncogene tyrosine-protein kinase (SRC), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), suggesting their potential involvement in modulating inflammation. Experimental results confirmed that 5,7,4′-trimethoxyflavone and 3,5,7-trimethoxyflavone significantly inhibited keratinocyte proliferation, migration, and macrophage activation, key processes in psoriasis progression. Additionally, both compounds reduced nitric oxide production, supporting their anti-inflammatory effects. Western blot analysis further demonstrated that these compounds tended to decrease the phosphorylation levels of AKT and SRC, supporting their role in influencing inflammatory signaling pathways. These findings suggest that methoxyflavones from KP act through multi-target mechanisms, offering potential as natural therapeutic agents for psoriasis. Further, in vivo studies are needed to validate their efficacy and explore their clinical applications.

MicroRNA (miRNA)-guided gene silencing depends on the accurate assembly and regulation of the RNA-induced silencing complex (RISC), in which Argonaute-2 (Ago2) interacts with accessory proteins to facilitate complex stability and catalytic activity. Staphylococcal nuclease domain-containing protein 1 (SND1) is an important component of the RISC and a transcriptional co-regulator implicated in multiple cancers; however, the structural consequences of disease-associated SND1 mutations remain poorly understood. In this study, an integrated computational workflow combining protein–protein docking, molecular dynamics simulations, and free energy analyses was employed to investigate the potential structural effects of the SND1 S781F mutation on the SND1–Ago2 interaction. The wild-type complex was predicted to maintain a stable interaction network involving the Tudor domain of SND1 and methylated arginine residues of Ago2. In contrast, the S781F substitution was associated with altered intermolecular hydrogen bonding patterns, reduced predicted interaction stability, increased structural flexibility, altered correlated residue motions, and a broader free energy landscape, suggesting a less stable protein–protein interface. Although the mutant complex sampled a larger number of distinct intermolecular hydrogen bond interactions, these interactions exhibited lower occupancies and reduced persistence than those in the wild-type complex. Collectively, these computational findings suggest that the S781F mutation could act as a potential modulator of the local physicochemical environment, interaction stability, and conformational dynamics of the SND1–Ago2 surface. This study provides atomistic insights into the structural consequences of the S781F mutation and establishes a computational framework for future experimental validation of its role in miRNA-mediated gene regulation and cancer biology.

Ultraviolet B (UVB) irradiation is a major environmental factor contributing to skin photoaging by inducing oxidative stress, apoptosis, inflammation, and extracellular matrix degradation in dermal fibroblasts. This study investigated the photoprotective effects of Thua Nao, a Thai fermented soybean, against UVB-induced human dermal fibroblast damage, and explored its underlying mechanisms. The dichloromethane fraction of Thua Nao (TN-DC) most effectively mitigated UVB-induced cell death. HPLC analysis identified daidzein and glycitein as the major constituent isoflavones in TN-DC that protect fibroblasts against UVB-induced cellular damage. Mechanistically, they reduced apoptosis by suppressing caspase-9 and poly (ADP-ribose) polymerase activation and preserving mitochondrial membrane potential. Additionally, they suppressed inflammatory mediators including interleukin-6, interleukin-8, inducible nitric oxide synthase, and cyclooxygenase-2 and prevented collagen loss. These protective outcomes correlated with decreased intracellular reactive oxygen species and upregulated endogenous antioxidant enzymes including superoxide dismutase 1 and heme oxygenase. Signaling pathway analysis revealed that TN-DC activated the pro-survival extracellular-signal-regulated kinase and Akt pathways in UVB-exposed cells. Conversely, daidzein and glycitein selectively attenuated c-Jun N-terminal kinase activation, downregulating downstream pro-inflammatory cytokines and mediators. Collectively, these findings demonstrate that TN-DC protects human dermal fibroblasts against UVB-induced photoaging primarily by enhancing endogenous antioxidant defense, thereby preserving cellular homeostasis through coordinated regulation of oxidative stress-responsive signaling pathways.

The increasing prevalence of multidrug-resistant Staphylococcus aureus (MRSA) has necessitated the development of alternative therapeutic strategies targeting bacterial virulence factors. This study employed an integrated in silico approach to identifying potential inhibitors of the iron-regulated surface determinant B Near-iron Transporter domain, a key protein involved in heme acquisition and pathogenicity. Virtual screening and molecular docking identified certain similarity-selected small molecules possessing strong binding affinities, with (4-(1-oxoisoindolin-2-yl)benzoic acid (TOP1) and (4-(2-oxochromen-3-yl)benzoic acid (TOP2) exhibiting the most favorable binding energies at −12.0 and −11.8 kcal/mol, respectively. Molecular dynamics simulations over 200 ns confirmed stable protein–ligand interactions that yielded reduced structural fluctuations in ligand-bound complexes when compared with the apo form. Molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) analysis revealed that van der Waals interactions were the primary contributors to binding, with TOP1 showing a more favorable overall binding energy. Drug-likeness and pharmacokinetic predictions indicated compliance with Lipinski’s rule of five and moderate bioavailability, although limited intestinal absorption was observed. Toxicity predictions indicated that both compounds are non-mutagenic but may exhibit hepatotoxicity. Notably, TOP1 exhibited potential nephrotoxicity, cardiotoxicity, and carcinogenicity, whereas TOP2 demonstrated a more favorable safety profile. These findings highlight a trade-off between binding affinity and safety, suggesting that TOP2 emerged as a computationally prioritized candidate for future experimental validation. Because the present findings represent computational predictions only, further orthogonal computational analyses and experimental studies are required to confirm the proposed binding modes, biological activity, and therapeutic potential of the identified compounds.

Osteoporosis is a prevalent skeletal disorder characterized by excessive bone resorption and an increased risk of fragility fracture. Cathepsin K (CatK), a lysosomal cysteine protease predominantly expressed in osteoclasts, is an established target for anti-resorptive drug development. Here, an integrated computational workflow comprising virtual screening, molecular docking, 300 ns molecular dynamics (MD) simulations, molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) calculations, and drug-likeness/ADMET prediction was used to prioritize natural product-derived CatK ligands from the MEGxM database. Among approximately 6500 screened compounds, TOP1 (PubChem ID: 97043052) and TOP2 (PubChem ID: 135765825) showed docking scores of −8.2 and −7.8 kcal/mol, respectively, compared with −6.6 kcal/mol for the comparative reference ligand (STD). Both compounds satisfied Lipinski’s rule of five; however, their predicted ADMET profiles were mixed, including negative predictions for human intestinal absorption for both compounds and compound-specific metabolic and toxicity liabilities. The 300 ns MD trajectories indicated broadly stable CatK ligand complexes. TOP1 showed slightly lower mean RMSD)/RMSF values than TOP2. In contrast, TOP2 exhibited more favorable MM/PBSA binding free energies than TOP1 at both analyzed intervals (−83.45 ± 10.06 and −80.74 ± 10.18 kJ/mol for TOP2 versus −74.28 ± 10.08 and −57.21 ± 15.04 kJ/mol for TOP1), while STD showed the most favorable MM/PBSA binding free energies overall. Collectively, TOP1 and TOP2 exhibited complementary computational profiles and should therefore be regarded as candidates for biochemical and cellular validation rather than confirmed CatK inhibitors or orally suitable drug leads.