Caffeine is a widely consumed psychoactive compound known to influence drug metabolism and efficacy through interactions with key enzymes such as cytochrome P450 3A4 (CYP3A4). This study investigates the molecular impact of caffeine on the binding behavior of imatinib, a first-line BCR-ABL tyrosine kinase inhibitor, using molecular docking simulations. Structural optimization and lipophilicity analyses were conducted using HyperChem, while docking was performed with HEX software (Version 8.0.0) against the CYP3A4 receptor (PDB ID: 1W0E). Two administration scenarios were evaluated: concurrent caffeine–imatinib complex formation and sequential administration with caffeine pre-bound to CYP3A4. The caffeine–imatinib complex exhibited a predicted increase in lipophilicity (logP = 3.09) compared to imatinib alone (logP = −1.29), which may indicate the potential for enhanced membrane permeability and tissue distribution. Docking simulations revealed stronger binding affinity of the complex to CYP3A4 (−350.53 kcal/mol) compared to individual compounds, and improved imatinib binding when CYP3A4 was pre-complexed with caffeine (−294.14 kcal/mol vs. −288.19 kcal/mol). Frontier molecular orbital analysis indicated increased reactivity of the complex (ΔE = 7.74 eV), supporting the hypothesis of altered pharmacodynamic behavior. These findings suggest that caffeine may modulate imatinib’s metabolic profile and therapeutic efficacy by enhancing receptor binding and altering drug distribution. The study underscores the importance of evaluating dietary components during drug development and therapeutic planning, particularly for agents metabolized by CYP3A4.

Peripheral nerve injuries, particularly those involving the sciatic nerve, remain a major clinical challenge due to incomplete functional recovery and the limited translation of preclinical advances into effective therapies. This review synthesizes current evidence on the phase-specific evaluation of sciatic nerve regeneration in preclinical models, integrating behavioral, sensory, electrophysiological, and morphological approaches across the acute, subacute (Wallerian degeneration), early regenerative, and late regenerative phases. By mapping functional readouts onto the underlying biological events of each phase, we highlight how tools such as the Sciatic Functional Index, Beam Walk test, Rotarod test, nerve conduction studies, and nociceptive assays provide complementary and often non-interchangeable information about motor, sensory, and neuromuscular recovery. We further examine emerging therapeutic strategies, including intraoperative electrical stimulation, immunomodulation, platelet-rich plasma, bioengineered scaffolds, conductive and piezoelectric conduits, exosome-based hydrogels, tacrolimus delivery systems, and small molecules, emphasizing the importance of aligning their mechanisms of action with the dynamic microenvironment of peripheral nerve repair. Despite substantial advancements in experimental models, an analysis of publication trends and registries reveals a persistent translational gap, with remarkably few clinical trials relative to the high volume of preclinical studies. To illustrate how mechanistic insights can be complemented by molecular-level characterization, we also present a targeted computational analysis of alpha-lipoic acid (ALA,) including frontier orbital energies, physicochemical descriptors, and docking interactions with IL-6, TGF-β, and a growth-factor receptor—performed solely for this molecule due to its documented structural availability and relevance. By presenting an integrated, phase-specific framework for functional assessment and therapeutic evaluation, this review underscores the need for standardized, biologically aligned methodologies to improve the rigor, comparability, and clinical relevance of future studies in sciatic nerve regeneration.

The aim of this study was to investigate the molecular interactions of heparin, diclofenac, and their supramolecular complexes with cyclooxygenase enzymes (COX-1 and COX-2) using computational docking techniques. Diclofenac is a widely used nonsteroidal anti-inflammatory drug (NSAID) that inhibits COX isoforms, whereas heparin is a polyanionic glycosaminoglycan with established anticoagulant and emerging anti-inflammatory properties. Supramolecular association between these agents may modulate their physicochemical behavior and target engagement. Molecular modeling, dual-drug docking, and molecular dynamics (MD) simulations were employed to characterize the interactions of heparin, diclofenac, and pre-formed heparin–diclofenac complexes with COX-1 and COX-2. Geometry optimization and lipophilicity (logP) estimates were obtained using HyperChem, while protein–ligand docking was performed in HEX using crystallographic COX structures from the Protein Data Bank. Docking poses were analyzed in Chimera, and selected complexes were refined through short MD simulations. Pre-formed heparin–diclofenac assemblies exhibited markedly enhanced docking scores toward both COX isoforms compared with single ligands. Binding orientation strongly influenced affinity: for COX-1, the heparin–diclofenac configuration yielded the most favorable interaction, whereas for COX-2 the diclofenac–heparin configuration was preferred. Both assemblies adopted binding modes distinct from free diclofenac, suggesting cooperative electrostatic and hydrophobic contacts at the enzyme surface. Supramolecular complexation also altered calculated logP values relative to the individual compounds. MD simulations supported the relative stability of the top-ranked complex–COX assemblies. These findings indicate that heparin–diclofenac assemblies may enhance and reorganize predicted COX interactions in a configuration-dependent manner and illustrate the utility of dual-drug docking for modeling potential synergistic effects. Such insights may inform the design of localized or topical formulations, potentially incorporating non-anticoagulant heparin derivatives, to achieve effective COX inhibition with reduced systemic exposure. However, the results rely on simplified heparin fragments, legacy docking tools, and short MD simulations, and should therefore be interpreted qualitatively. Experimental studies will be essential to confirm whether such supramolecular assemblies form under physiological conditions and whether they influence COX inhibition in vivo.

The incorporation of plant-derived oils into cosmetic formulations has attracted increasing interest due to their natural origin, skin compatibility, and multifunctional formulation roles. Argan and castor oils are widely used in cosmetic products as emollient lipid components with intrinsic antioxidant properties. However, limited studies have systematically evaluated the physicochemical stability and antioxidant performance of emulsions combining these two oils. The aim of this study was to develop and comprehensively characterize a stable oil-in-water (O/W) cosmetic emulsion based on argan and castor oils using a natural non-ionic emulsifier (C14–22 Alcohol (and) C12–20 Alkyl Glucoside). Particular emphasis was placed on formulation stability, as it represents a critical prerequisite for further product evaluation. Stability was investigated through thermal stress testing (4–37 °C), centrifugation assays, droplet size analysis, and zeta potential measurements. Complementary physicochemical and structural characterization was performed using rheological analysis and Fourier transform infrared (FT-IR) spectroscopy. The formulated emulsion exhibited good physical stability with no phase separation under the tested conditions, a skin-compatible pH, a uniform droplet size distribution (4.15 ± 0.68 µm), and pseudoplastic, moderately thixotropic rheological behavior. Antioxidant capacity was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, yielding an IC₅₀ value of 19.21 ± 1.02 mg/mL. Overall, this study provides a formulation-oriented framework for the development and evaluation of stable natural oil-based O/W emulsions intended for cosmetic applications, supporting future optimization and biological validation.

This study provides a comparative evaluation of two Salvia species, the widely cultivated Salvia sclarea L. and the comparatively underexplored wild species Salvia pratensis L., integrating phytochemical profiling, chemical safety assessment, and biological activity investigation. Dried hydroethanolic extracts and essential oils obtained from aerial parts were analysed. HPLC–PDA analysis revealed distinct phenolic acid profiles, with S. sclarea characterized by higher levels of rosmarinic and protocatechuic acids, whereas S. pratensis contained greater amounts of hydroxycinnamic acids such as caffeic, p-coumaric, and ferulic acids. The total phenolic content was higher in S. pratensis (79.22 mg GAE/g dry extract) than in S. sclarea (52.50 mg GAE/g). GC–MS analysis showed that the essential oil of S. sclarea was dominated by oxygenated monoterpenes, mainly linalyl acetate and linalool, while S. pratensis exhibited a linalool-rich profile accompanied by sesquiterpene derivatives. Chemical safety assessment indicated minimal contamination, with pesticide residues detected only in S. sclarea at levels below regulatory limits and low concentrations of cadmium and lead in both species. The extracts showed strong antioxidant activity (DPPH IC₅₀ values of 6.67 µg/mL for S. sclarea and 3.16 µg/mL for S. pratensis) and moderate broad-spectrum antimicrobial activity (MIC 312.5–2500 µg/mL). In vitro assays on HEK 293 and HaCaT cells confirmed low cytotoxicity, with no evidence of membrane damage or pro-inflammatory effects. Overall, the results highlight the significant bioactive potential of the less studied S. pratensis, demonstrating that this wild species represents a promising alternative source of natural antioxidant and antimicrobial compounds comparable to the widely cultivated S. sclarea.

Multifunctional dressings capable of maintaining a moist environment, supporting tissue regeneration, and delivering bioactive compounds are increasingly being explored as promising strategies for burn wound management. In this study, alginate-based emulgel patches incorporating hydrophilic and lipophilic plant extracts were developed by extrusion-based 3D printing as potential topical systems for burn wound applications. The formulation included sodium alginate, hyaluronic acid, and hydroglyceric extracts of Calendula officinalis, Matricaria chamomilla, and Plantago major, as well as oily extracts of Hippophae rhamnoides and Hypericum perforatum. The emulgel was evaluated for pH, rheological behaviour, spreadability, physical stability, apparent hydrodynamic size distribution, zeta potential, total polyphenol content, and antioxidant activity. Following Ca²⁺-induced crosslinking, uniform and flexible 3D-printed patches were obtained and further characterised for pharmacotechnical, physicochemical, structural, functional, and biological properties. The emulgel exhibited suitable characteristics for extrusion-based printing, while the resulting patches showed good dimensional uniformity, flexibility, swelling capacity, water vapour transmission, and surface pH compatible with topical application. FTIR, DLS, SEM, and SEM–EDX analyses supported the formation of a Ca²⁺-crosslinked alginate network and confirmed the presence of structurally heterogeneous domains with homogeneous calcium distribution. The patches retained plant-derived bioactive compounds, with a total polyphenol content of 0.2878 ± 0.016 mg GAE/g hydrated patch, and showed improved antioxidant activity compared with the corresponding emulgel. In vitro release studies indicated the time-dependent diffusion of polyphenols over 24 h, with cumulative release reaching 64.42%. The patches also exhibited a water vapour transmission rate of 1270 ± 93 g/m²/24 h, indicating adequate moisture regulation. HaCaT cell viability remained above 90% at lower tested concentrations, demonstrating a favourable biocompatibility profile. Overall, the developed 3D-printed alginate emulgel patches represent promising multifunctional systems for potential burn wound management and warrant further preclinical investigation.