Search Results (267)

The adoption of exhaust gas cleaning systems (scrubbers) in maritime transport generates a complex metal-laden washwater that may pose a noteworthy threat to marine ecosystems. This study assessed the acute toxic effects (LC₅₀, 48 h) of four prevalent metals detected in scrubber washwater—vanadium (V), iron (Fe), nickel (Ni), and zinc (Zn)—both individually and as a realistic mixture. For this purpose, multiple life stages of Artemia franciscana (nauplii, juveniles, and adults) and the rotifer Brachionus plicatilis have been tested under laboratory conditions. All metals induced concentration-dependent toxicity, but sensitivities varied through life stages and species tested. The sensitivity to contaminants generally decreased as the organism’s developmental stage progressed. Consequently, three different orders of toxicity can be detected. The order of metal toxicity (from highest to lowest toxicity, based on 48 h LC₅₀ values) was V > Fe > Ni > Zn for nauplii; V > Zn > Fe > Ni for juveniles and adults; and Fe > V > Zn > Ni for B. plicatilis. The Cumulative Toxic Unit (CTU) approach was utilized to compare the predicted additive effect with observed mixture toxicity. This analysis revealed a complex, life stage-dependent interaction; while antagonism dominated in nauplii (suggesting chemical mitigation), juveniles and adults of A. franciscana and the rotifer (B. plicatilis) exhibited significant synergism, amplifying the total toxicity beyond prediction. This study demonstrates that early life stages and small zooplankton are the most sensitive bioindicators of scrubber-related metal contamination, highlighting the potential ecological risk posed by metal-rich, acidic scrubber discharges that may enhance metal bioavailability and toxicity in marine environments. Full article

Background: Toxic epidermal necrolysis (TEN) is a rare but life-threatening complication that may occur in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in the context of extensive drug exposure. In this population, TEN can closely resemble severe acute graft-versus-host disease (GVHD), making diagnosis and management challenging. Case presentation: We report the clinical course of an allo-HSCT recipient who developed a rapidly progressive skin rash early after transplantation, and we analyzed the clinical features, histopathology, treatment and outcome. Results: The patient developed rapidly progressive epidermal detachment with severe oral, ocular, and genital mucosal involvement shortly after exposure to trimethoprim/sulfamethoxazole (TMP-SMX). Disease severity was reflected by a SCORTEN score of 5, corresponding to a very high predicted mortality risk. The clinical picture raised concern for both TEN and severe acute GVHD, while histopathological findings favored TEN but were not definitive. Management included systemic corticosteroids, intravenous immunoglobulin, ruxolitinib, and intensive supportive care. The patient gradually re-epithelialized and recovered without long-term sequelae. Conclusions: This case underscores the diagnostic difficulty of distinguishing TEN from severe acute GVHD in the early post-transplant period. Careful assessment of drug exposure, clinical evolution, and multidisciplinary evaluation are essential to guide timely and appropriate management. Full article

M8OI is a cytotoxic methylimidazolium ionic liquid solvent through its binding to the ubiquinone binding site on complex I of the mitochondrial electron transport chain. Given the overlap in terms of toxic mechanism of action with the pesticide rotenone, the potential neurotoxic effects of M8OI were examined. In vitro, cytotoxicity and mitochondrial function were assessed in SH-SY5Y cells by measuring MTT reduction and oxygen consumption/extracellular acidification using a Seahorse analyser. SH-SY5Y cells were sensitised to M8OI toxicity by replacing medium glucose with galactose. Glucose protected the cells from M8OI toxicity, whereas galactose showed no clear dose–response protection. M8OI induced a dose-dependent reduction in oxygen consumption rate with a compensatory increase in extracellular acidification rate, consistent with inhibition of mitochondrial oxidative phosphorylation and a shift toward glycolysis. In vivo, rats were orally exposed via drinking water for 20 weeks and assessed using behavioural tests. In addition, the concentrations of M8OI and its metabolites were quantified by LC–MS in rat brain and other tissues. In rats, M8OI concentrations were ~30-fold higher in kidney than brain, and brain levels were at least 100-fold lower than the concentrations that affected SH-SY5Y cell viability in vitro. However, based on open field tests, M8OI exposure suppressed motor activity without any anxious behaviours. The cytotoxicity of M8OI in SH-SY5Y neuroblastoma cells was associated with metabolic mitochondrial dysfunction. However, the neurobehavioural changes observed in orally exposed rats occurred at significantly lower brain concentrations than would be predicted to lead to neural cell death. Nevertheless, direct comparisons between acute in vitro exposures and chronic in vivo outcomes should be interpreted cautiously. Full article

Essential oils obtained from Siparuna plants, e.g., S. guianensis and S. gesnerioides, have potential for use as biorational insecticides. However, the activities of S. gesnerioides oils remain largely unexplored compared to S. guianensis oils. Using an integrative approach combining toxicological bioassays, geometric morphometrics, and in silico modeling, we assessed the adulticidal potential, selectivity, and the effects of early-life exposure to these oils on the larval susceptibility and adult wing morphometry of Aedes aegypti. Adulticidal assays revealed high toxicity, with S. guianensis (LC₅₀ = 15.0 nL/mL) being 15-fold more potent than S. gesnerioides (LC₅₀ = 233.0 nL/mL). Beyond acute lethality, early-life (i.e., eggs to L2 larvae) exposure to sublethal concentrations (S. guianensis = 7.4 nL/mL and S. gesnerioides = 118.0 nL/mL) was associated with wing morphometric disruptions and increased fluctuating asymmetry in Ae. aegypti adults, especially in those exposed to S. gesnerioides essential oil. Furthermore, early-life exposure to S. gesnerioides modulated L4 larvae susceptibility, which was associated with lower mortality in subsequent exposures. Selectivity assays demonstrated low acute oral toxicity in initial laboratory screenings with Apis mellifera, while molecular docking approaches predicted higher affinity of bicyclogermacrene and α-copaene for Ae. aegypti TRPV channels. Collectively, while S. gesnerioides oil was less acutely toxic, early-life sublethal exposures reduced fourth instar larvae (L4) susceptibility, which may have contributed to developmental instability and morphological alterations in adults. Our findings highlight the potential of Siparuna essential oils in mosquito management by impacting mosquito fitness beyond acute mortality. Full article

Research on oxazolones, particularly 4-alkynyloxazolones, has garnered increasing interest due to the presence of an alkynyl group, which facilitates molecular conjugation and enables diverse chemical modifications. In this study, three representative 4-alkynyloxazolone derivatives (L1–L3) were synthesized and structurally characterized through single-crystal X-ray diffraction and computational analysis to obtain a reliable structure of L1–L3 to subsequently predict in silico interactions with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein. The crystallographic results revealed high molecular planarity and multifurcated hydrogen bonding. Considering the obtained crystallographic structure, theoretical descriptors such as HOMO–LUMO energy gaps and electrostatic potential maps indicated that these compounds exhibit favorable electronic reactivity, particularly for L3, with favorable drug-like predictions. The lack of methoxy groups in L2 and L3 makes these compounds have lower predicted toxicity parameters than L1. Molecular docking calculations targeting SARS-CoV-2 spike glycoprotein in three different feasible conformations in a biological matrix, i.e., three receptor-binding domains (RBD) in down conformation, two RBD in down and one in up conformation, as well as RBD bound to the human receptor angiotensin-converting enzyme 2 (ACE2), suggested strong binding affinities and specific interactions with the RBD moiety, mainly in the up conformation. Overall, this work integrates crystallographic and computational approaches to establish the structural and in silico evaluation of spike-binding properties of early substituted 4-alkynyloxazolones, suggesting L3 as a candidate for future in vitro antiviral assays. Full article

Background: Post-remission cytarabine consolidation is a cornerstone of therapy for acute myeloid leukemia (AML), but the optimal dosing strategy in older adults (≥60 years) remains unclear. High-dose cytarabine (HiDAC) is often avoided due to toxicity concerns, and data guiding cumulative dosing are limited. Methods: We conducted a single-center retrospective cohort study of 111 patients aged ≥60 years with AML who achieved complete remission after standard 7 + 3 induction and received at least one cycle of cytarabine consolidation between 2012 and 2024. A 90-day landmark analysis excluded early relapses or deaths. Results: The median age was 65 years; 41% proceeded to allogeneic hematopoietic stem cell transplantation (allo-SCT). Cytarabine consolidation was well tolerated, with no neurotoxicity and only one instance of reversible nephrotoxicity. Patients were stratified by median cumulative cytarabine dose into low-intensity (<18 g/m², LIC) and high-intensity (≥18 g/m², HIC) groups. HIC was associated with improved overall survival compared with LIC (median OS: 31 vs. 13 months, p = 0.02), particularly among non-transplanted patients (25 vs. 7 months, p = 0.01). On multivariable analysis, HIC (HR 0.71, 95% CI 0.51–0.82, p = 0.01) and allo-SCT (HR 0.58, 95% CI 0.44–0.79, p = 0.03) independently predicted superior survival. Conclusions: Higher cumulative cytarabine consolidation is safe, feasible, and associated with improved survival in older AML patients, especially among patients ineligible for transplant. Prospective studies are warranted to define the optimal dosing strategy in this population. Full article

Quantitative structure–activity relationship (QSAR) modeling has conventionally relied on expert-designed molecular descriptors to encode chemical structures. DeepSnap is a descriptor-free QSAR approach that converts prepared three-dimensional molecular conformers into image representations and feeds them directly into convolutional neural networks for activity prediction. This focused narrative review traces DeepSnap from its introduction in 2018 to its current state and places it within the broader landscape of descriptor-based QSAR, topology-based and 3D-aware graph neural networks, and related image-based or semi-image-based molecular representation approaches. Previous studies applied DeepSnap to Tox21 nuclear receptor and molecular initiating event endpoints, rat hepatic clearance, blood–brain barrier penetration, acute oral toxicity, and cosmetics–pharmaceutical compound classification. Across the DeepSnap series, image-based and descriptor-based predictions have provided complementary information, particularly in ensemble or consensus models. However, high or near-ceiling ROC–AUC values reported for selected endpoints should not be interpreted as indicating deterministic or universally generalizable predictions; rather, they should be considered in the context of endpoint-specific model development, image-rendering parameter optimization, possible class imbalance, split dependence, limited matched external replication, and incomplete benchmarking against modern molecular representation models. Limitations include a dependence on nonphysical rendering parameters, single- or representative-conformer input, incomplete matched benchmarking against 2D and 3D molecular representation models, and an interpretability gap addressed in part by CAM-family visualization in the AI-based Substance Hazard Integrated Prediction System (AI-SHIPS) and S-COPHY (a model developed by Shiseido for cosmetics–pharmaceutical compound classification). Future directions include standardized image-generation protocols, conformer-ensemble extensions, systematic interpretability analysis, matched benchmarking, and potential integration with graph-based and 3D-aware molecular learning approaches. Full article

Background: Safer analgesic strategies are needed to reduce the adverse effects associated with prolonged use of nonsteroidal anti-inflammatory drugs. The dry juice extract of Agave tequilana (ESPA), a chemically complex matrix with anti-inflammatory potential, may represent a promising adjuvant for modulating inflammatory pain. Objective: This study evaluated the antinociceptive activity of ESPA and its pharmacological interaction with diclofenac in the formalin test. Methods: BALB/c mice received ESPA or diclofenac orally 30 min before pain induction, and nociceptive behavior was quantified by counting paw flinches during the neurogenic and inflammatory phases. The GC–MS-detectable fraction of ESPA was chemically characterized, while the pharmacokinetic and bioactivity profiles of selected compounds were explored in silico using SwissADME and PASSonline. Molecular docking with COX-1 and COX-2 was performed using AutoDock Vina. Acute toxicity was evaluated according to OECD Guideline 423, and the ESPA–diclofenac interaction was examined using isobolographic analysis. Results: ESPA produced significant antinociceptive effects during the inflammatory phase. Although diclofenac exhibited greater potency, ESPA showed consistent efficacy in reducing inflammatory nociceptive behavior. GC–MS analysis identified several compounds within the detectable volatile/lipophilic fraction, including n-hexadecanoic, octadecanoic, and oleic acids. In silico evaluations suggested favorable predicted oral absorption and potential bioactivities related to inflammatory mediator regulation. Docking studies showed moderate predicted affinities for COX-1 and COX-2, lower than those observed for diclofenac. Isobolographic analysis demonstrated a synergistic interaction between ESPA and diclofenac, allowing dose reduction while maintaining antinociceptive efficacy. Acute toxicity testing indicated no signs of toxicity at the evaluated dose. Conclusions: These findings suggest that ESPA may act as a potential adjuvant in diclofenac-based analgesic strategies for inflammatory pain; however, further studies are required to clarify the active constituents and underlying mechanisms. Full article

Dissolved organic matter (DOM) in algae-laden micro-polluted source water is highly complex, posing major challenges to drinking water treatment and risk control. However, the molecular fate of DOM and its associated toxicity consequences under different treatment processes remains insufficiently understood. In this study, a multi-scale characterization approach combined with toxicity prediction was used to systematically compare the effects of coagulation, ozonation, and adsorption on the molecular transformation and toxicity evolution of DOM. FT-ICR MS analysis assigned 1092 DOM molecular formulae in the raw water, while 741 and 800 assigned formulae remained after coagulation and adsorption, respectively. Both processes showed distinct molecular selectivity: saturated molecules were preferentially removed by both treatments, whereas coagulation showed a stronger preference for oxidized molecules. By comparison, ozonation achieved limited COD_Mn and DOC reduction but markedly reduced UV₂₅₄ and increased the number of assigned molecular formulae to 1500. The ozonated effluent was characterized by diverse transformation products, especially oxidized saturated small molecules, accompanied by enhanced bio-origin fluorescence signals and more prominent low-molecular-weight neutral and biopolymer fractions. In addition, ozonation increased the numbers of highly acute and highly chronic toxic molecules by 53.60% and 42.25%, respectively, whereas coagulation and adsorption reduced these high-risk molecules. These findings reveal the process-specific molecular transformation and toxicity evolution of DOM under three classical water treatment processes, providing a theoretical basis for process optimization and ecological risk control. Full article

This study evaluates volatile extracts (HE1 and HE2) from the lichen Pseudevernia furfuracea as eco-friendly agents to control algal proliferation, specifically targeting the cyanobacterium Microcystis aeruginosa and the green microalga Chlorella sorokiniana. Both extracts exhibited potent anti-microalgal activity against the two species with a minimum inhibitory concentration (MIC) ranging from 375 to 750 µg/mL. Furthermore, both extracts reduced cell density by more than 98% after eight days of treatment. Chlorophyll a and protein levels decreased significantly (>80%) in both species, indicating suppression of pigment synthesis. However, their physiological responses were distinct: M. aeruginosa underwent early acute oxidative stress and severe membrane damage, while C. sorokiniana exhibited delayed oxidative activation and a negative growth rate, suggesting non-lytic metabolic inhibition. An in silico study by molecular docking of the most abundant compounds identified in these volatile extracts, such as terpenoids (abietatriene, δ-cadinene) and a phenolic compound (atraric acid), showed that these compounds interact with vital cellular targets in M. aeruginosa and C. sorokiniana and likely contribute to the effects observed in these two species. Predictive toxicity by applying the ADMET framework confirmed the favorable bioavailability and low acute toxicity of these volatile compounds. Therefore, P. furfuracea volatiles are promising, species-specific, and environmentally safe candidates for mitigating aquatic algal proliferation through targeted oxidative and metabolic interference. Full article

Leishmaniasis remains a major neglected tropical disease with limited therapeutic options, challenged by drug toxicity and emerging resistance to current treatments like miltefosine. In this study, a virtual library of approximately 150 azole-derived compounds was screened in silico to identify promising thiazole and imidazole scaffolds, leading to the rational design of novel hybrid molecules. Molecular docking against thioredoxin reductase (PDB ID: 4CBQ), a key enzyme in the redox metabolism of Leishmania mexicana, showed improved binding affinity compared to miltefosine, with compound 3f showing the most favourable interaction profile. Among the synthesized series 3a–f, compound 3f (4-NO₂Ph) exhibited the most favourable predicted binding parameters within the series (∆G = −16.08, Ki = 0.0019 nM). Biological evaluation was performed against L. mexicana promastigotes as an early-stage phenotypic screening model to identify active compounds with potential relevance during the initial infective phase, and a markedly improved in vitro inhibitory effect (IC₅₀ = 22.41 µM) compared to miltefosine (IC₅₀ = 132.42 µM), representing a six-fold increase in molar potency. Furthermore, hybrid thiazolyl–imidazole systems (series 3) consistently outperformed single-core analogues, likely due to enhanced molecular planarity and lipophilicity provided by the imine linkage. Cytotoxicity assays in Vero cells revealed a high safety margin for the lead compounds, with compound 3f achieving a Selectivity Index (SI) of around 89, significantly outperforming the reference drug. Acute toxicity studies (LD₅₀) in murine models further confirmed the safety profile, with values exceeding 2000 mg/kg for the most active derivatives. These findings identify thiazolyl–imidazole hybrids as promising early-stage scaffolds for antileishmanial drug discovery, particularly for early infection/prophylactic screening. Full article

Pterostilbene (Pts), a small molecule stilbenoid and a dimethyl analogue of the star molecule resveratrol, exerts significant blood–brain barrier protection on cerebral ischemia-reperfusion injury and has received extensive attention. This study performed structural optimizations on Pts to obtain a series of derivatives and investigated their anti-ischemic activities both in vitro and in vivo, aiming to identify candidates with high safety and improved efficacy compared with Pts. The ADMET method was used to predict the drug-likeness of a series of Pts derivatives, and in vitro MTT cell viability analysis was conducted on neuroblastoma cells (SH-SY5Y) and brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation/reperfusion (OGD/R) injury. On the basis of the cytotoxicity results, four derivatives (NO. 1, NO. 3, NO. 5, and NO. 7) were selected for subsequent in vitro and in vivo biological activities evaluation. These compounds exhibited significantly higher TI values (18.29–30.61) in OGD/R-injured hBMECs compared with Pts (7.63) and effectively suppressed apoptosis, promoted cell migration, and enhanced tube formation capacity. In vivo, NO. 3 (5 mg/kg, ip., 7 d) demonstrated superior efficacy compared to Pts in improving cerebral blood flow, reducing infarction volume, enhancing neurological function, and modulating serum biomarker levels in middle cerebral artery occlusion/reperfusion (MCAO/R) rats, whereas NO. 1 and NO. 7 showed comparable efficacy to Pts. The acute intraperitoneal toxicity of NO. 3 was conducted and showed that the LD₅₀ of NO. 3 was estimated to be more than 300 mg/kg. In this study, the rational design and comprehensive evaluation of Pts derivatives were reported. Compound NO. 3 demonstrated superior pharmacological efficacy to Pts both in vitro and in vivo, and it may be a promising therapeutic candidate for ischemic stroke intervention. Full article

Spi-1 Proto-Oncogene (SPI1) encodes Purine-rich box 1 Transcription Factor (PU.1), a transcription factor of the ETS family that regulates hematopoietic lineage commitment and immune cell differentiation. Alteration of PU.1 dose or ETS domain integrity may interfere with transcriptional programs, which adds to hematopoietic dysregulation and leukemogenesis. Even though changes in SPI1 expression have been associated with acute myeloid leukemia (AML), the structural and regulatory effects of missense mutations at the PU.1 ETS domain have not been entirely studied, and targeting the PU.1 ETS domain by ligands is an area of computational analysis that should be further pursued. To computationally describe deleterious missense variants of SPI1 in terms of structural stability, evolutionary conservation, post-translational modification (PTM) context and interaction networks, and to measure ADMET-mediated molecular docking of cinnamic acid with the PU.1 ETS domain (8EQG) as a potential modulator. Missense nsSNPs were obtained through Ensembl and narrowed down by consensus prediction of pathogenicity (PredictSNP, combining SIFT, PolyPhen, SNAP and PhD-SNP and other tools). InterPro/UniProt was used for domain mapping. SWISS-MODEL was used to produce wild-type and mutant PU.1 versions, which were analyzed on the structural alignment and Cα–Cα displacement parameters in UCSF Chimera (v1.19). The estimation of stability change was carried out with I-Mutant and MUpro. Prediction of PTM sites was done using MusiteDeep and exploration of functional partners was done using STRING. Human, mouse and zebrafish orthologue conservation was measured by means of MAFFT alignment. GEPIA2 was used to compare the expression of SPI1 in AML (TCGA-LAML) and normal tissues (GTEx). AutoDock Vina (grid center 6, −2, −9 A; 20 × 20 × 20 A; 16 exhaustiveness) was used to prepare cinnamic acid and dock it into the PU.1 ETS domain (8EQG), with SwissDock being used for consistency checks. SwissADME and ADMETlab 2.0 were used to predict drug-likeness, pharmacokinetics, and toxicity. Nine missense mutations were routinely considered as deleterious with the majority of them being located in or near the ETS DNA-binding domain. Structural comparisons showed local perturbations of the structure and I189F and H211P yielded the greatest conformational changes between prioritized variants whereas other forms had minimal movements. A predominantly destabilizing trend was supported by stability prediction whereby V241G had the strongest destabilization signal with further destabilizations being predicted in I189F and R259C. PTM mapping revealed several potential regulatory residues (phosphorylation, acetylation, ubiquitination, and methylation), which indicated that there could be crosstalk between the sequence variation and the transcriptional regulation. The SPI1 was placed in a central hematopoietic transcriptional module (containing RUNX1, CEBP members, GATA1 and IRF factors) by the STRING network. The cross-species alignment showed that there was high conservation of a number of the mutation sites, which would support functional constraint at the ETS region. The expression analysis revealed that the level of SPI1 mRNA in AML was significantly elevated compared to normal tissues. Docking also indicated a slight and reproducible interaction of cinnamic acid with the ETS domain (top affinity −4.27 kcal/mol), with a solitary leading polar anchor and supportive hydrophobic interactions, which is akin to interaction between fragments. The ADMET profiling revealed the likelihood of success in the oral drug-likeness and low CYP inhibition liability, as well as signifying the presence of a possible hepatotoxicity signal that needs further confirmation through experiments. Comprehensive computational studies suggest that certain pathogenic variants of SPI1 missense defects, especially in the ETS domain, can result in loss of PU.1 structural stability and regulatory environment, which are in line with the disturbed hematopoietic regulation and AML-related dysregulation. Cinnamic acid demonstrates moderate yet reproducible binding to the PU.1 ETS domain and has an overall favorable developability profile, which indicates that it is better considered as a starting scaffold, as opposed to an active inhibitor. The results give a logical basis of focused biochemical validation and structure-directed optimization of ETS domain modulators in hematologic disease settings. Full article

The combination of thiopurine and methotrexate (MTX) is a standard co-therapy regimen for acute lymphoblastic leukemia (ALL). Despite its efficacy, this regimen is constrained by a narrow therapeutic window and considerable inter-individual variability, which heightens the risk of drug-induced liver injury (DILI). MTX-induced metabolic strain further destabilizes cytokine-sensitive thiopurine detoxification pathways during systemic inflammation. Conventional pharmacogenetic (PGx) testing for TPMT and NUDT15 variants is effective in predicting myelosuppression, but often fails to detect hepatotoxicity as an adverse effect, suggesting a clinically significant genotype-phenotype difference. This review examines the molecular determinants of DILI, emphasizing the role of secondary metabolic pathways and transporter dynamics as key modulators of risk. The study describes cytokine-mediated (IL-6, TNF-α) transcriptional suppression of cytochrome P450 enzymes and hepatic transporters (SLCO1B1, ABCC2/4) not merely as secondary modulators, but as the primary determinants of localized, tissue-specific drug exposure through disrupted nuclear receptor signaling (PXR, CAR, HNF4α). This mechanism promotes functional phenoconversion and toxic molecular shunting, leading to increased intrahepatic drug exposure. It synthesizes the current knowledge on the metabolism of thiopurine and MTX, focusing on the genetic and non-genetic factors influencing toxicity and their interactions. The review also critically evaluates the limitations of static PGx-guided dosing. It highlights the need for comprehensive, real-time risk assessment that integrates gene-environment interactions, multi-omics data, and clinical monitoring to improve precision therapy for ALL. This approach combines extended PGx profiling, transcriptomic monitoring, and clinical biomarker assessment to provide a transformative strategy for precision drug delivery. Full article

Schoenoplectus californicus, a macrophyte from Peruvian marine–coastal wetlands, is traditionally used for medicinal purposes, yet its pharmacological potential remains insufficiently explored. This study evaluated the chemical profile, antioxidant capacity, psychopharmacological effects, and analgesic activity of a hydroethanolic extract from its rhizomes. Phytochemical screening and LC–MS/MS analyses were performed to characterize secondary metabolites. Antioxidant activity was assessed using DPPH and ABTS assays, while in vivo anxiolytic, sedative, and analgesic effects were evaluated in Balb/c mice through open field, elevated plus maze, rotarod, analgesimeter, tail-flick, and hot plate tests, with diazepam and tramadol as reference drugs. In silico PASS and BOILED-Egg analyses were used to predict pharmacological mechanisms and central nervous system permeability. The extract contained flavonoids, phenolic compounds, and stilbenes and exhibited notable antioxidant activity (IC₅₀: 0.7319 mg/mL for DPPH and 0.6207 mg/mL for ABTS). Anxiolytic effects were observed at 50 mg/kg, sedative effects at 200 mg/kg, and significant analgesic activity at 50 mg/kg. Several compounds were predicted to cross the blood–brain barrier, with inhibition of GABA aminotransferase suggested as a potential mechanism. Acute toxicity was detected (LD₅₀ > 2000 mg/kg). These findings support S. californicus as a promising source of neuroactive and analgesic compounds, although further mechanistic and dose-optimization studies are required. Full article