Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by cholinergic dysfunction, oxidative/nitrosative stress, and neuroinflammation. Marine green algae Caulerpa racemosa are rich in neuroactive lipids and fatty acid derivatives with reported antioxidant and anti-inflammatory properties. However, their integrated mechanistic potential against AD remains largely underexplored. This study aimed to elucidate the neuroprotective mechanisms of C. racemosa metabolites against AD using integrative metabolomics, network pharmacology, molecular docking, and in vitro validation assays. Untargeted LC–HRMS profiling was performed to identify major metabolites in the ethanolic extract of C. racemosa. Neuroprotective targets were predicted via TargetNet, STRING, and Cytoscape (MCODE, CytoNCA). Functional enrichment was conducted using KEGG, GO (BP, MF, CC), and ClueGO. Molecular docking (CB-Dock2) validated compound–target interactions with ACHE, CHRM1, NOS1, and NOS2. Antioxidant (DPPH) and cholinesterase (AChE/BChE) inhibitory activities were evaluated in vitro. Metabolomic profiling identified lipid-dominant metabolites—oleamide, hexadecanamide, palmitoyl ethanolamide, α-linolenic acid, α-eleostearic acid, and 9-oxo-octadecadienoic acid. Network analysis revealed key AD-related hubs (ACHE, CHRM1, NOS1, NOS2) enriched in cholinergic regulation, arachidonic-acid metabolism, oxidative stress response, and nitric oxide signaling. Docking showed moderate multi-target affinities (−6.0 to −8.4 kcal/mol), with α-linolenic acid, α-eleostearic acid, and oxidized C18 lipids exhibiting the strongest interactions—particularly with ACHE and NOS isoforms. In vitro assays showed moderate antioxidant activity (IC₅₀ = 120.97 ± 10.93 µg/mL) and cholinesterase inhibition (AChE IC₅₀ = 136.48 ± 1.70 µg/mL; BChE IC₅₀ = 145.98 ± 3.28 µg/mL), aligning with predicted multi-target interactions. C. racemosa extract exhibits neuroprotective potential through a synergistic combination of cholinergic modulation, antioxidant activity, NOS-mediated nitrosative stress reduction, and suppression of arachidonic-acid inflammatory pathways. These findings support C. racemosa as a promising marine-derived multi-target candidate for AD intervention, warranting further mechanistic and in vivo evaluation.

Oyster mushroom ( Pleurotus ostreatus ) is recognized as a functional food due to its bioactive compounds content which have therapeutic potential, particularly in metabolic disorder management. This study aims to explore the bioactive profile of oyster mushroom flour (OMF) using a multi-omics approach to evaluate its antioxidant, antiobesity, and antidiabetic properties. A comprehensive multi-omics approach has been employed, integrating metabolomics and proteomics profiling using LC-HRMS and Orbitrap mass spectrometry. In vitro assays assessed antioxidant capacity through ABTS and superoxide dismutase (SOD) activity, antiobesity potential via lipase inhibition and 3T3-L1 adipocyte assays, and antidiabetic effects via α-glucosidase, α-amylase, and dipeptidyl peptidase-4 (DPP-4) inhibition tests. In silico analysis further mapped molecular interactions and pathways. Metabolomic profiling identified 376 unique compounds and 13 peptides, including antioxidants, and enzyme inhibitors, contributing to antiobesity and antidiabetic effects. Proteomic analysis revealed peptides targeting metabolic pathways associated with oxidative stress and glucose regulation. γ-tocotrienol, estriol, kynurenic acid, and palmitoylcarnitine exhibited strong binding affinities with key metabolic targets, suggesting their potential as natural inhibitors for diabetes and obesity management. In vitro assays confirmed the oyster mushroom radical scavenging activity, lipase inhibition, and enzymatic modulation capabilities, with strong support from in silico analyses mapping molecular targets and pathways. These findings suggest P. ostreatus as a natural resource for managing metabolic disorders and developing evidence-based functional foods. This research bridges the gap between compound discovery and therapeutic application, paving the way for its broader utilization in nutraceuticals and precision nutrition strategies.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder requiring safe, multitarget therapeutic strategies. Marine macroalgae represent an underexplored source of bioactives with pleiotropic metabolic effects. This study investigated the antidiabetic potential of an ultrasound-assisted ethanolic extract of Caulerpa racemosa (UAECr) and its key phytosterol, campesterol, through an integrative framework combining metabolomics, network pharmacology, molecular docking, molecular dynamics simulation, and in vitro validation. Untargeted ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC–HRMS) metabolomics characterized UAECr constituents, followed by in silico bioactivity prediction, target-network analysis, molecular docking, and 100 ns molecular dynamics simulation of the peroxisome proliferator-activated receptor gamma (PPARγ)–campesterol complex. Functional validation was performed in differentiated 3T3-L1 adipocytes assessing glucose uptake, PPARγ expression, dipeptidyl peptidase 4 (DPP-4) inhibition, and cytotoxicity. Metabolomics identified campesterol as a prominent bioactive. Network pharmacology highlighted PPARγ as a central hub, supported by strong docking affinity of campesterol toward PPARγ (−11.4 kcal/mol) and DPP-4 (−8.3 kcal/mol). Molecular dynamics simulations demonstrated stable PPARγ–campesterol interactions, with preserved protein compactness and low residue fluctuation. In vitro, UAECr and campesterol significantly enhanced glucose uptake (up to 134% vs. control, p < 0.001), upregulated PPARγ expression (4-fold, p < 0.0001), and moderately inhibited DPP-4 activity (p < 0.01) without cytotoxicity. C. racemosa-derived extracts and campesterol exert antidiabetic effects primarily via stable PPARγ-mediated insulin sensitization with complementary DPP-4 modulation, supporting its potential as a marine-derived functional food candidate.

Osteosarcoma remains the most common primary malignant bone tumor in adolescents and is characterized by aggressive metastasis, resistance to therapy, and extensive bone microenvironment remodeling. Therefore, the identification of novel multi-target therapeutic agents capable of simultaneously inducing ferroptosis and disrupting tumor-supportive signaling is urgently needed. This study employed a multi-omics-guided approach to investigate the anti-osteosarcoma potential of metabolites derived from the sea cucumber Holothuria scabra. LC–MS/MS profiling identified major bioactive constituents, including holothurins, scabrasides, fucosterol, desmosterol, and 24-methylenecholesterol. Integrated transcriptomic analysis of the GSE42352 dataset revealed key ferroptosis- and bone microenvironment-associated targets, including CXCR4, CTSK, RUNX2, VEGFA, and TFRC. In silico pharmacological prediction and molecular docking demonstrated favorable anticancer properties and strong binding affinities of several metabolites toward these targets, with fucosterol and holothurin A exhibiting the most promising interactions. Functional validation in MG-63 osteosarcoma cells showed concentration-dependent reductions in cell viability and migration following H. scabra treatment. Furthermore, treatment decreased GPX4, NRF2, and GSH levels while increasing TFRC and MDA, indicating activation of ferroptotic cell death. In a MG-63/RAW264.7 co-culture model, H. scabra suppressed RANKL, VEGFA, MMP9, and TRAP-positive osteoclast formation, suggesting inhibition of osteoclastogenesis, angiogenesis, and metastatic potential. Collectively, these findings identify H. scabra as a promising marine source of multi-target compounds for osteosarcoma management through coordinated induction of ferroptosis and remodeling of the bone tumor microenvironment.

The argan tree (Argania spinosa) is an endemic Moroccan species known for its primary product, argan oil, which possesses exceptional nutritional and medicinal properties. The current study aimed to evaluate and compare the antidiabetic and antioxidant activities of argan oil obtained from the introduced and native argan tree in eastern Morocco, to analyze its chemical composition using HPLC-DAD and GC-MS, and to investigate the molecular mechanisms behind the obtained pharmacological activities through an in silico pharmacological networking and molecular docking study. The results revealed that argan oil from all three regions of Morocco (Oujda, Agadir, and Chouihya) is rich in oleic and linoleic acids as major constituents, along with the presence of significant tocopherols. Regarding the antioxidant assays, including DPPH radical scavenging and iron-reducing power tests, argan oil from Oujda exhibited the highest activity, with the lowest IC₅₀ values of 15.25 ± 0.022 mg/mL and 28.5 ± 1.7 mg/mL, respectively. Concerning the antidiabetic activity, we found that oil from Chaouihya showed the strongest α-amylase inhibition, while Oujda oil had the highest antiglycation activity, indicating that even introduced argan trees retain potent bioactivity. The results of the in silico investigation suggested that tocopherols may contribute to the antioxidant and antidiabetic potential of argan oil, showing predicted antioxidant activity (Pa = 0.843–0.967) and favorable binding affinities toward iNOS (ΔG = −9.3 kcal mol⁻¹) and α-glucosidase (ΔG = −8.2 kcal mol⁻¹). The identified fatty acids also showed predicted insulin-promoting activity (Pa = 0.59–0.75) and moderate enzyme-binding potential. Pharmacological network analysis identified 51 shared genes associated with antioxidant, antidiabetic, and argan-related targets, with enrichment of the AGE–RAGE signaling pathway. These computational findings provide possible molecular associations that may help explain the observed biological activities, although they remain predictive and require experimental validation. Overall, the in silico analysis suggests that tocopherols could be among the contributors to the multi-target profile of Argania spinosa oil, while fatty acids may provide complementary effects related to glycemic regulation.