Search Results (361)

Aim of the Study: The aim of this study was to characterize the volatile phytochemical composition of Cannabis sativa L. essential oil (CSEO) and evaluate its in vitro inhibitory activity against selected digestive enzymes and its antiglycation activity. Molecular docking and ADMET analyses were additionally performed to explore the possible interactions and predicted pharmacokinetic properties of the major identified constituents. Materials and Methods: The chemical composition of CSEO was characterized by Gas Chromatography–Mass Spectrometry (GC-MS). Its in vitro inhibitory activity was evaluated against α-amylase, α-glucosidase, and pancreatic lipase, while its antiglycation activity was assessed by monitoring the formation of glycation products at different stages of the glycation process. Molecular docking simulations were performed to investigate the potential interactions of major identified terpenes with the active sites of the investigated enzymes. In addition, ADME analysis was conducted to predict selected pharmacokinetic and drug-likeness properties of the major constituents. Results: gc-ms analysis revealed a complex terpenoid profile, with β-caryophyllene as the major constituent, followed by selina-3,7(11)-diene (8.00%), cubenol (6.62%), γ-eudesmol (6.57%), epiglobulol (6.04%), and valencene (5.80%). CSEO showed significant in vitro inhibitory activity against α-amylase, α-glucosidase, and pancreatic lipase. The essential oil also exhibited antiglycation activity, with inhibition observed at different stages of glycation-product formation. Molecular docking analysis indicated that several major sesquiterpenes could interact with the investigated enzyme targets through different binding interactions. ADME analysis provided predicted pharmacokinetic and drug-likeness profiles for the major constituents. Conclusions: The findings demonstrate that Cannabis sativa L. essential oil possesses in vitro digestive-enzyme inhibitory and antiglycation activities. The docking results provide molecular-level insights into possible interactions between major essential-oil constituents and the investigated enzyme targets. These findings support further investigation of CSEO and its major constituents using appropriate in vivo and mechanistic studies to determine their biological relevance and potential applications. Full article

Acne vulgaris is a multifactorial inflammatory disorder involving bacterial colonization, oxidative stress, and lipid-mediated inflammation, necessitating a comprehensive multitarget approach. This study evaluated the anti-acne potential of five morphological parts of Limonia acidissima L. using an integrated in vitro and in silico approach. Ultrasound-assisted extracts were evaluated for antibacterial activity against Cutibacterium acnes and Staphylococcus epidermidis, antioxidant activity using DPPH and ABTS assays, and total phenolic and flavonoid contents (TPC and TFC). TOPSIS was applied to minimize selection bias and identified the leaf extract as the optimal candidate (closeness coefficient = 0.88325). LC-MS/MS tentatively identified major metabolites, including vitexin, quercetin, cyanidin-3-O-galactoside, caffeate, methyleugenol, indole, and linolenic acid. Molecular docking predicted favorable interactions of linolenic acid with C. acnes KAS III (Rerank Score = −78.470) and 15-lipoxygenase (15-LOX) (Rerank Score = −101.025), as well as cyanidin-3-O-galactoside with S. epidermidis (Rerank Score = −109.588) and KEAP1 (Rerank Score = −132.253). SwissADME analysis further suggested favorable drug-likeness and skin-permeation profiles. Collectively, these findings support the potential of L. acidissima leaf extract as a promising multitarget anti-acne candidate. Full article

The triterpenoid and polysaccharide constituents of Ganoderma lucidum (GL) are believed to influence key pathogenic pathways in Alzheimer’s disease (AD). This study first examined the molecular rationale for GL’s neuroprotective properties by subjecting its principal triterpenoids, Ganoderic Acid A&B, to computational profiling. Molecular docking was performed against human acetylcholinesterase (AChE), TNF-α, COX-2, IL-6, caspase-3, Bcl-2, and the Keap1–Nrf2 complex using CB-Dock2, alongside SwissADME-based physicochemical and ProTox-3.0-based toxicological screening. These targeted pathways were then biologically validated in an in vitro AD model induced by Aβ_1–42 toxicity in SH-SY5Y cells, assessing AChE activity, apoptosis, ROS levels, mitochondrial membrane potential (MMP), and cytokine expression (COX-2, TGF-β1, IL-6, TNF-α, IL-10). Docking revealed high binding affinities of both triterpenoids toward all seven targets (Vina scores: −7.3 to −10.4 kcal/mol), predicting strong modulation of cholinergic, inflammatory, apoptotic, and antioxidant pathways. Consistent with these predictions, GL extract significantly reduced TNF-α, COX-2, and IL-6 mRNA and protein levels, attenuated ROS accumulation, preserved MMP except at 500 µg/mL, and exerted a concentration-dependent antiapoptotic effect. IL-10 and TGF-β1 showed complex, dose-dependent patterns, reflecting indirect regulatory responses. Together, these findings support GL’s neuroprotective potential against Aβ-induced toxicity through direct engagement of cholinergic, inflammatory, apoptotic, and antioxidant regulatory proteins. Full article

Folate-mediated one-carbon metabolism supports nucleotide biosynthesis, methylation reactions, and redox homeostasis, and the mitochondrial enzyme MTHFD2 has emerged as a cancer-associated metabolic target. However, the development of MTHFD2-preferential inhibitors remains challenging because MTHFD2 is structurally and functionally related to other folate-metabolism enzymes, including the cytosolic enzyme MTHFD1 and the mitochondrial isoenzyme MTHFD2L. In this study, a curated library of 115 phytochemicals was screened against the folate/substrate-binding pockets of MTHFD2 and MTHFD1 using a redocking-controlled molecular-docking protocol. Three compounds, dehydrotrametenolic acid, eburicoic acid, and rutaecarpine, met the docking-based prioritization criteria for predicted MTHFD2-preferential binding. Subsequent ADME, drug-likeness, and toxicity profiling indicated that the two triterpenoids had unfavorable physicochemical and pharmacokinetic properties and were therefore not advanced to biochemical testing, whereas rutaecarpine showed the most balanced predicted profile. In vitro enzyme-inhibition assays showed that rutaecarpine inhibited both MTHFD2 and MTHFD1 in a concentration-dependent manner. Rutaecarpine inhibited MTHFD2 with an apparent IC₅₀ of 31.35 μM and MTHFD1 with an apparent IC₅₀ of 54.20 μM, corresponding to a modest 1.73-fold preference for MTHFD2. In contrast, the reference antifolate LY345899 preferentially inhibited MTHFD1. These findings identify rutaecarpine as a natural-product scaffold with statistically supported but modest MTHFD2-preferential activity and support its further structure-guided optimization, including future profiling against MTHFD2L. These results should be interpreted as evidence of exploratory scaffold-level activity rather than identification of a potent, optimized, or broadly validated MTHFD2 inhibitor. Full article

Background: Catheter ablation is the most effective rhythm-control strategy for symptomatic atrial fibrillation (AF). A fluoroless approach eliminates ionizing radiation exposure for patients, operators, and laboratory staff and removes the ergonomic burden of leaded protective garments. Pulsed field ablation (PFA) is a predominantly non-thermal energy modality with a distinct safety profile, now addressed in dedicated international consensus documents. Several PFA catheters are natively integrated with three-dimensional electroanatomical mapping (3D EAM) platforms and are therefore well suited to fluoroscopy-free workflows. This review is confined to two of them—Sphere-9 (Affera/Medtronic) and VARIPULSE (Biosense Webster)—with which the authors have direct procedural experience. Objective: This study seeks to describe a practical, expert- and experience-based approach to zero-fluoroscopy AF ablation with these two catheters, to review the harms of radiation exposure, and to synthesize the currently available and still limited evidence for fluoroless PFA. The workflow presented is explicitly not an evidence-validated or broadly generalizable algorithm, and each procedural step is labeled according to whether it rests on comparative data, device-specific studies or instructions for use, or institutional practice and expert opinion. Methods: This is a structured narrative review. PubMed/MEDLINE was searched to 30 June 2026 (final search 30 June 2026), with no lower date restriction, using controlled vocabulary and free-text terms for atrial fibrillation, catheter ablation, zero or minimal fluoroscopy, pulsed field ablation, Sphere-9, Affera, and VARIPULSE. English-language randomized trials, cohorts, registries, systematic reviews, and society documents reporting procedural or clinical outcomes were eligible; reference lists were hand-searched. Conference abstracts, preprints, and non-peer-reviewed manufacturer reports were excluded from all numerical statements. Results: Four meta-analyses report comparable acute success, arrhythmia recurrence, and complication rates between zero-fluoroscopy and fluoroscopy-guided AF ablation, with procedural feasibility of 95.1% and a crossover rate of 1.26%. These are pooled observational comparisons without pre-specified non-inferiority designs or margins, and they should not be read as establishing formal non-inferiority. Differences between them reflect ablation technology, imaging strategy, study period, operator experience, and heterogeneous definitions of “zero fluoroscopy”. Randomized evidence comparing PFA with thermal ablation shows comparable 12-month efficacy and major complication rates and shorter procedure duration but no consistent reduction in fluoroscopy time—a finding that bears directly on the present topic. Sheath visualization is the decisive enabler: in a randomized trial of 100 patients, left atrial fluoroscopy time was 0 s (IQR 0–0) with a visualizable steerable sheath. In a nonrandomized subgroup analysis of the AdmIRE trial, 12-month freedom from AF was similar across zero- (72.1%), low- (75.4%) and conventional-fluoroscopy (73.6%) strategies. Conclusions: Integration of PFA with 3D EAM and intracardiac echocardiography makes a fluoroless workflow practical in experienced hands. The supporting evidence remains predominantly observational; no randomized trial has compared zero-fluoroscopy with fluoroscopy-guided PFA, and the approach described here should be regarded as expert practice rather than a standard of care. Patient safety, not the absolute avoidance of fluoroscopy, must remain the governing principle. Full article

This study investigated the neuroprotective potential of Xanthoceras sorbifolium Bunge (XSB) seed oil through fatty acid profiling, antioxidant assays, and in silico targeting of FABP7. Among the solvent-to-solid ratios tested, 1:20 (w/v) gave the highest oil yield (72.91%) and the strongest ABTS, DPPH, and FRAP activities. GC-MS identified 17 fatty acids from the 1:20 (w/v) oil extract, with linoleic acid (38.93%) and oleic acid (31.3%) as the major constituents. Following GC-MS fatty acid profiling, lipid structural characterization was performed using ¹H NMR and FT-IR. ADME/T prediction and BOILED-EGG analysis suggested favorable pharmacokinetic properties and BBB permeability for the selected fatty acids. Molecular docking and simulation revealed strong and stable interactions of five compounds with FABP7: nervonic acid (−6.1 kcal/mol), erucic acid (−6.002 kcal/mol), eicosadienoic acid (−6.08 kcal/mol), oleic acid (−6.03 kcal/mol), and linoleic acid (−6.00 kcal/mol), outperforming the native ligand, oleic acid (−5.8 kcal/mol). These findings indicate that XSB seed oil contains bioactive lipids with promising FABP7-targeted neuroprotective potential and warrant further investigation as therapeutic leads for neurodegenerative diseases. Full article

Background: Building on earlier work with methoxy-, dimethoxy-, bromo-, and nitro-substituted salicylaldehyde benzoylhydrazones, we synthesized and evaluated new 4-chloro- and 5-chloro derivatives bearing an additional chlorine substituent on the hydrazide-derived phenyl ring to further explore the impact of halogenation on cytotoxic activity. Methods: Chloro-hydrazones were obtained through a one-step condensation of 4- or 5-chlorosalicylaldehyde with benzhydrazide or 2-, 3-, and 4-chlorobenzhydrazides. Their physicochemical, pharmacokinetic, ADME, lead-likeness, and drug-likeness profiles were evaluated in silico using SwissADME, ACD/Labs v9.10, and MDL QSAR v2.2.0.0.446. The synthesized compounds were structurally characterized by IR, ¹H NMR, ¹³C NMR, and HR ESI–MS, and their cytotoxic activity was subsequently assessed by the MTT assay in selected cancer cell lines. Molecular docking was performed against ABL1 tyrosine kinase (ABL1 TK), a potential molecular target relevant to two of the investigated leukemia cell lines, using GOLD v.5.2.2 (CCDC Ltd., Cambridge, UK). Results: The chloro-substituted salicylaldehyde benzoylhydrazones exhibited pronounced, cell-type-dependent cytotoxicity, with leukemia cells being substantially more sensitive than breast carcinoma cells. Most derivatives showed low- to sub-micromolar IC₅₀ values against SKW-3 human T-cell prolymphocytic leukemia, K-562 human chronic myeloid (myelogenous) leukemia, and BV-173 human BCR::ABL1-positive leukemia cells, with K3 and K4 exhibiting the highest activity in SKW-3 cells (IC₅₀ = 0.5 ± 0.1 µM). K5 showed particularly strong activity against K-562 and BV-173 cells (IC₅₀ = 0.7 ± 0.1 and 0.9 ± 0.1 µM, respectively), compared with 26.9 ± 2.4 and 21.5 ± 3.3 µM for imatinib. HL-60 human acute promyelocytic leukemia cells showed intermediate sensitivity (IC₅₀ = 1.3–13.9 µM), whereas the activity against MCF-7 estrogen receptor-positive and MDA-MB-231 triple-negative breast carcinoma cells was more variable (1.5–32.1 and 4.1–62.5 µM, respectively). The derivatives showed high selectivity toward malignant cells relative to non-malignant CCL-1 non-malignant mouse fibroblasts, with lower-bound SI values frequently exceeding 50 and reaching >200 in SKW-3 cells. Conclusions: The chloro-substituted salicylaldehyde benzoylhydrazones exhibited pronounced and selective cytotoxicity, particularly toward leukemia cell lines, identifying this scaffold as a promising starting point for further anticancer drug-discovery studies. Full article

The persistent global threat posed by emerging and re-emerging RNA viruses, including SARS-CoV-2, influenza A(H1N1)pdm09, DENV-2, and CHIKV, highlights the critical need for novel and broad-spectrum antiviral agents. Building upon the established antiviral activity of the quinoline scaffold, this study employed a molecular hybridization strategy to design and synthesize a novel series of 1,2,3-triazole–quinoline derivatives (compounds 4a–4h). This approach strategically fused the bioactive quinoline nucleus with the pharmaceutically favorable 1,2,3-triazole ring. The new compounds were synthesized efficiently in three steps with moderate-to-high yields, and their structures were subsequently determined. Their inhibitory capacities against the four viruses and cytotoxicity across relevant cell lines were evaluated in vitro. The initial screening demonstrated that compounds 4a–4h possessed broad-spectrum antiviral activity, showing high inhibition percentages at 10 µM against SARS-CoV-2, DENV-2, and CHIKV. Notably, compounds 4c and 4e, substituted with methoxy and ethyl groups, respectively, displayed exceptional potency and safety against SARS-CoV-2, yielding high selectivity indices (SI: 1896.5 and 1265.8, respectively). Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) and molecular docking calculations suggested favorable drug-likeness profiles, including improved lipophilicity and non-P-glycoprotein substrate feasibility. The findings validate the molecular hybridization strategy, establishing this new class of compounds as promising, multi-target antiviral prototypes for further preclinical exploration against prevalent viral pathogens. Full article

Background: Paclitaxel is a cornerstone chemotherapeutic agent widely used in breast cancer treatment, primarily through the stabilization of microtubule dynamics. Beyond its canonical tubulin-targeting activity, increasing evidence suggests that paclitaxel may engage additional molecular targets, contributing to its complex pharmacological profile. In this study, an integrated computational workflow was applied to evaluate the structural compatibility between paclitaxel and the neurokinin-2 receptor (NK2R), a G protein-coupled receptor involved in tumor-associated inflammatory and proliferative signaling pathways. Physicochemical profiling and target prediction were performed using SwissADME and SwissTargetPrediction, followed by molecular docking and molecular dynamics simulations using AutoDock Vina and GROMACS 2024.1. Paclitaxel exhibited physicochemical properties consistent with transient interactions in hydrophobic transmembrane environments. Docking analysis identified a plausible binding mode within the NK2R transmembrane cavity, primarily stabilized by hydrophobic contacts. Molecular dynamics simulations over 100 ns revealed stable ligand occupancy and overall complex stability, while MM-PBSA calculations indicated a favorable transient association. The predicted interaction is consistent with secondary or non-canonical receptor engagement. While NK2R is not established as a pharmacological target of paclitaxel, the results support the structural feasibility of a previously uncharacterized receptor interaction and provide a reproducible computational framework for exploring GPCR-associated effects of cytotoxic agents. Full article

Background/Objectives: Human carbonic anhydrase (CA) isoforms are clinically relevant zinc metalloenzymes, but their highly conserved catalytic Zn²⁺ site makes isoform-selective inhibitor design challenging. This study developed an explainable multi-isoform QSAR workflow for prioritizing selective inhibitors of human CA I, CA II, CA IX, and CA XII, integrating PubChem experimental concordance and applicability-domain (AD) analysis to distinguish model-supported candidates from exploratory extrapolative hypotheses. Methods: Curated ChEMBL K_i datasets were standardized to pK_i and modeled in KNIME using 4185 two-dimensional descriptors, Random Forest-based feature selection, and H2O.ai AutoML stacked ensembles. A matched 3200-compound four-isoform matrix supported direct selectivity profiling. Potent ChEMBL inhibitors (K_i < 10 nM) seeded 90% PubChem similarity expansion; analogues were scored across all four isoform-specific models, while PubChem records were filtered to retain only human isoform-specific K_i evidence. AD was calibrated using Morgan fingerprint similarity, descriptor-space distance, and leverage analysis. Candidates were prioritized by predicted potency, selectivity, SAR plausibility, SwissADME profile, structural alerts, and AD membership. Results: Models achieved held-out R² values of 0.727, 0.719, 0.652, and 0.607 for CA I, CA II, CA IX, and CA XII, respectively. PubChem concordance identified 1098 prioritized compounds with assay records, including 847 with direct K_i evidence and 428 with complete four-isoform coverage; same-target agreement showed Pearson r > 0.86 and linear-fit R² > 0.74. Test-set error rose from very-high-AD to low/out-of-domain classes. Conclusions: The workflow integrates QSAR prediction, PubChem concordance, explainable SAR, ADME triage, and AD-based reliability assessment. CA II and CA XII candidates showed the strongest support, CA IX showed intermediate support, and CA I candidates require cautious interpretation as low-domain exploratory hypotheses. Full article

The search for sustainable feed ingredients has increased interest in insect-derived proteins for livestock production. This study evaluated the effects of replacing 3% soybean meal with house cricket (Acheta domesticus) meal on carcass traits, meat quality, proximate composition, and fatty acid profile of growing rabbits. Twenty-four weaned New Zealand White rabbits were assigned to either a control (CNT) or a cricket meal diet (ADM) from 35 to 85 days of age. Physical meat quality was evaluated in the Longissimus thoracis et lumborum (LTL), while proximate composition and fatty acid profile were determined in LTL and thigh muscles. Carcass performance was not affected by dietary treatment, whereas the cricket meal diet increased adiposity, resulting in greater scapular and perirenal fat deposition (p < 0.001) and a higher fat proportion in the hind leg (p = 0.011). Physical meat quality traits were unaffected, except for higher cooking loss in ADM-fed rabbits (p = 0.039). Cricket meal increased crude fat and modified the fatty acid composition by increasing n-6 PUFA (p = 0.013) and reducing n-3 PUFA (p < 0.001), resulting in a less favorable n-6/n-3 ratio. Overall, cricket meal modified lipid deposition and fatty acid composition without compromising carcass performance, although its greater lipid contribution should be considered when interpreting these effects. Full article

Although Atractylodes macrocephala Koidz. (AM) exhibits various pharmacological properties, its molecular effects and active constituents regarding anagen entry and physiological hair cycle progression remain uncharacterized. This study aimed to investigate the hair growth-promoting efficacy of AM and identify its bioactive compounds and underlying molecular mechanisms. We evaluated AM extract using human dermal papilla cells (DPCs) and a synchronized depilation-induced C57BL/6 mouse model, employing RT-PCR, Western blotting, immunofluorescence, and SwissADME-based pharmacokinetic profiling. AM significantly enhanced DPC proliferation and migration while upregulating paracrine factors (HGF, VEGF, and FGF7). Mechanistically, AM activated Akt, ERK, and p38 MAPKs, leading to GSK3β phosphorylation (Ser9) and subsequent β-catenin stabilization. In vivo, oral AM (60 mg/kg) markedly accelerated the telogen-to-anagen transition, increasing dermal thickness, follicle count, and hair shaft quality without systemic toxicity. Furthermore, cell-based screening and SwissADME prioritized atractylenolide I and III as the chief bioactive sesquiterpenoids driving DPC activation. In conclusion, AM and its key atractylenolides promote anagen entry and hair regrowth, in association with GSK3β phosphorylation and β-catenin stabilization, representing promising natural candidates for promoting physiological hair cycle progression. Full article

This study investigated the effects of terpene compounds from Schinus molle fruit essential oil (EO) against osteoarthritis (OA) using integrated network pharmacology, molecular docking, and molecular dynamics. The EO, obtained by steam distillation (yield: 6.95%), was characterized by GC-MS, detecting 55 peaks (98.61% of the total), of which 49 were identified and dominated mainly by monoterpene hydrocarbons (73.93%), with α-phellandrene (20.35%), camphene (11.36%), and Z-β-ocimene (8.69%) as the major constituents. Additionally, seven compounds with favorable ADME profiles and low predicted toxicity were selected for the target prediction. Overlap analysis between compound targets and osteoarthritis-related genes (Os-teoDIP) revealed 171 common genes that triggered inflammatory pathways, including PI3K-Akt, HIF-1, and NOD-like receptor signaling. Protein–protein interaction network analysis identified 11 hub genes, including TLR4, HSP90AA1, PTGS2, and MAPK1. Molecular docking revealed that γ-cadinene exhibited the best binding affinities, particularly against HSP90AA1 (−6.38 kcal/mol) and TLR4 (−5.87 kcal/mol). A 200 ns molecular dynamics simulation confirmed the stability of the γ-cadinene–TLR4 complex through persistent hydrophobic contacts with residues F379, C391, F409, I310, and F377, with contact occupancy of up to 0.95. The receptor backbone RMSD plateaued between 2.5 and 3.5 Å after equilibration, and the ligand remained in the binding pocket throughout the trajectory. These findings suggest that the terpenes of S. molle EO, particularly γ-cadinene, may modulate the inflammatory pathways related to OA. However, it is necessary to complement experimental validation in vitro and in vivo. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder involving metabolic impairment, neuroinflammation, synaptic failure, and comorbidities. Hence, therapeutic development for AD is rapidly shifting from a single-target approach, centred on amyloid-beta (Aβ) reduction, to multi-target strategies. In this study, we investigated the neuroprotective profile of two acetanilide derivatives, SG-22 and SG-23, originated from the halogen-free thyronamine-like lead compound SG-2. Their efficacy was evaluated through an integrated approach combining in vitro cellular models, in vivo phenotypic screening in a Caenorhabditis elegans AD model, and comprehensive ADME-Tox profiling. In U87MG cells, both SG-22 and SG-23 effectively prevented Aβ_25–35-induced cytotoxicity and restored autophagy-related gene expression, including LC3, SIRT1, and SIRT6, while reducing mTOR and SIRT5 levels. Furthermore, all compounds exhibited anti-inflammatory effects in activated HMC3 microglial cells, reducing IL-6 and increasing IL-10 levels, with evidence suggesting partial involvement of TAAR1 signalling. ADME-Tox analyses revealed improved safety and metabolic profiles for the tested compounds, particularly SG-22, which showed reduced hERG liability and enhanced cytochrome P450 stability. However, in vivo studies demonstrated that only SG-2 and SG-23 improved motility and fitness in the C. elegans AD model, consistent with their ability to activate autophagy, whereas SG-22 was ineffective due to limited organismal uptake. Ultimately, the monoacetylated analogue SG-23 emerges as a promising candidate, balancing neuroprotective efficacy and drug-like properties, and supporting thyronamine-like analogues as multi-target agents for AD. Full article

Background/Objectives: Sphagneticola trilobata is a phytochemically rich medicinal plant, yet its antioxidant-active fractions and redox-related mechanisms remain incompletely characterized. This study combined metabolite profiling, antioxidant screening, network pharmacology, pharmacokineticprediction, and molecular docking to characterize active flower and leaf fractions and prioritize antioxidant-related targets. Methods: Petroleum ether, methylene chloride, and ethyl acetate fractions of S. trilobata flowers and leaves were analyzed by ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC–ESI–MS/MS). The predominant metabolite was isolated and spectroscopically characterized. Antioxidant activity was assessed using 2,2′-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and ferric reducing antioxidant power (FRAP). Metabolites from the most active fractions were investigated by target prediction, protein–protein interaction (PPI) analysis, enrichment analysis, SwissADME, and docking. Results: UPLC–ESI–MS/MS tentatively identified 59, 18, and 16 metabolites in the petroleum ether, methylene chloride, and ethyl acetate fractions, respectively, including diterpenes, phenolic acids, flavonoids, fatty acids, triterpenes, and coumarin-related metabolites. Butein was isolated as the predominant metabolite from the ethyl acetate flower fraction, which showed the strongest antioxidant activity, with IC₅₀ values of 5.85 ± 0.14 µg/mL in ABTS and 9.11 ± 0.75 µg/mL in FRAP, followed by the ethyl acetate leaf fraction. Network analysis identified 61 and 82 antioxidant-relevant targets for the flower and leaf ethyl acetate fractions, respectively, with enrichment in inflammation-, apoptosis-, transcription-, hypoxia-, lipid stress-, and kinase-related pathways. Docking suggested fraction-specific compatibility with EGFR/PTGS2/STAT3 for flower metabolites and AKT1/PTGS2 for leaf metabolites. Conclusions: S. trilobata ethyl acetate fractions, particularly the flower fraction, represent promising antioxidant sources with experimentally supported activity and computationally prioritized redox-related hypotheses requiring further validation. Full article