Adina-Elena Segneanu

Plant-derived extracellular vesicles (PDEVs), engineered phytosomes, bioinspired polymeric plant-based nanoparticles (PBNPs), hybrid phyto-inorganic nanocomposites, green-synthesized metal nanoparticles, self-assembled nanoarchitectures, and multifunctional composites represent a rapidly advancing class of sustainable, nature-inspired nanocarriers. These platforms combine exceptional biocompatibility, negligible immunogenicity, and renewable sourcing with tunable drug loading, targeted delivery, and controlled release properties. This review synthesizes translational advances from 2020 to 2026, covering scalable isolation/bioprocessing (bioreactors, elicitation), multi-parametric physicochemical/multi-omics characterization, rational engineering/hybridization, and rigorous in vitro/in vivo assessments of uptake, biodistribution, pharmacokinetic (PK), and efficacy. Phytosomes and PBNPs markedly enhance oral bioavailability and targeted delivery of lipophilic phytochemicals, while PDEVs offer unique immunomodulatory, anti-inflammatory, and gene-regulatory activities. Hybrid and green-synthesized systems provide structural stability, redox modulation, and synergistic effects, and self-assembled/multifunctional composites address solubilization barriers with stimuli-responsive design. Early-phase human studies on grapefruit-, ginger-, turmeric-, and ginseng-derived PDEVs report excellent short-term safety, favorable PK, and preliminary bioactivity signals, with no observed immunogenicity or dose-limiting toxicities; however, these trials remain exploratory, constrained by small sample sizes and safety-focused endpoints. Despite challenges, including methodological heterogeneity, variable yields, long-term safety uncertainties (notably for inorganic hybrids), and regulatory ambiguities, emerging strategies such as clustered regularly interspaced short palindromic repeats (CRISPR)-engineered plant line; artificial-intelligence-driven process optimization; standardized guidelines, and integrated clinical, intellectual property, and commercialization frameworks are progressively addressing these barriers. Collectively, these advances position plant-derived nanocarriers as immunologically privileged, eco-friendly alternatives to synthetic and mammalian platforms, laying the foundation for a sustainable era of precision phytomedicine.

Galeopsis tetrahit L. (Lamiaceae) is a traditional European medicinal species rich in phenolic compounds, among which verbascoside is a key bioactive marker with strong antioxidant potential. This study reports the standardization of a G. tetrahit leaf extract in verbascoside using a fully validated UHPLC–PDA method developed according to ICH Q2(R2) requirements. Leaves of wild-grown G. tetrahit collected from southwest Romania flora were extracted with 70% ethanol, yielding 17.28% dry extract. Chromatographic identification of verbascoside was confirmed by retention time, UV–PDA spectra, and QDa mass spectrometry (m/z 623.3 [M–H]⁻). The method showed excellent performance, including high specificity, linearity over 1.875–60 μg/mL (r = 0.999955), low LOD and LOQ (0.2649 and 0.8028 μg/mL, respectively), and robust precision and accuracy. Dry extract contained 345.8 ± 28.3 mg verbascoside per g (34.6%, w/w), corresponding to approximately 59.8 mg/g in dried leaves. Antioxidant assays (DPPH, ABTS, FRAP), TPC and TFC confirmed notable radical scavenging and reducing activity, with pure verbascoside showing markedly stronger effects, supporting its major contribution to the extract’s antioxidant potential. These results demonstrate a reliable analytical approach and establish a verbascoside-based standardization framework for G. tetrahit extracts of documented Romanian origin.

Galeopsis tetrahit L. (Lamiaceae) is a traditional European medicinal species rich in phenolic compounds, among which verbascoside is a key bioactive marker with strong antioxidant potential. This study reports the standardization of a G. tetrahit leaf extract in verbascoside using a fully validated UHPLC–PDA method developed according to ICH Q2(R2) requirements. Leaves of wild-grown G. tetrahit collected from southwest Romania flora were extracted with 70% ethanol, yielding 17.28% dry extract. Chromatographic identification of verbascoside was confirmed by retention time, UV–PDA spectra, and QDa mass spectrometry (m/z 623.3 [M–H]^–). The method showed excellent performance, including high specificity, linearity over 1.875–60 μg/mL (r = 0.999955), low LOD and LOQ (0.2649 and 0.8028 μg/mL, respectively), and robust precision and accuracy. Dry extract contained 345.8 ± 28.3 mg verbascoside per g (34.6%, w/w), corresponding to approximately 59.8 mg/g in dried leaves. Antioxidant assays (DPPH, ABTS, FRAP), TPC and TFC confirmed notable radical scavenging and reducing activity, with pure verbascoside showing markedly stronger effects, supporting its major contribution to the extract’s antioxidant potential. These results demonstrate a reliable analytical approach and establish a verbascoside-based standardization framework for G. tetrahit extracts of documented Romanian origin.

Geranium spp. are recognized as rich sources of phenolic metabolites, with potential health benefits, yet comparative evaluations remain limited. We assessed four wild-grown Geranium spp. (G. dissectum—G1, G. lucidum—G2, G. pusillum—G3, and G. robertianum—G4), from southwestern Romanian flora, using complementary antioxidant (DPPH, ABTS, and FRAP) and phytochemical (TPC and TFC) assays. Targeted UHPLC/UV with MS confirmation quantified eight phenolic acids. FRAP provided the strongest discrimination between species, and mirrored TPC, with the highest values in G4 sample. ABTS and DPPH supported the same ranking, and TFC varied only modestly, but differences were narrower and not significant between species. Caffeic acid was highest in G1 sample, and chlorogenic acid was selectively elevated in G3 sample. Gallic and protocatechuic acids were highest in G4 sample, both tracking the FRAP/TPC gradient. Syringic acid and vanillic acid were enriched in weaker antioxidant species. Distinctive signatures included high p-coumaric acid in G4 sample and chlorogenic and ferulic acids in G3 sample. Antioxidant potential among Geranium spp. is best explained by TPC, particularly hydroxybenzoic acids, with FRAP emerging as the most sensitive discriminator. These findings provide a comparative benchmark for Geranium spp. phytochemistry and a framework for future pharmacological studies.

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a systemic condition with neuropsychiatric comorbidities, including depression. Growing evidence for the neuroprotective, antidepressant, and anxiolytic potential of Portulaca oleracea (PO) extract, provides a compelling rationale for investigating its effects in the interaction between dietary models of NAFLD and vulnerability to stress-related disorders. Fifty-four 14- to 18-week-old male and female C57BL/6N mice were distributed in two equal groups and fed either a methionine- and choline-deficient diet (MCD) or a methionine- and choline-controlled diet (MC). Subsequently, half of each group was subjected to chronic unpredictable mild stress (CUMS) and PO treatment. MCD caused significant weight loss, whereas MC promoted weight gain. Behaviorally, MCD induced anhedonia- and anxiety-like behaviors, worsened by CUMS. MC diet reduced CUMS-induced anhedonia, though anxiety-like behavior emerged only under stress. Recognition memory was impaired in stressed MCD-fed mice, while MC-fed mice showed enhanced novel object preference. At the cellular level, MCD suppressed hippocampal microglia and caused cortical astrocyte dysfunction, whereas the MC diet promoted cortical neurogenesis potentiated through PO, abolished by chronic stress. These findings underscore the impact of dietary composition on PO’s systemic effects under chronic stress and support a mechanistic link between NAFLD-related dysfunction and depression-like phenotypes.

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a systemic condition with neuropsychiatric comorbidities, including depression. Growing evidence for the neuroprotective, antidepressant, and anxiolytic potential of Portulaca oleracea (PO) extract, provides a compelling rationale for investigating its effects in the interaction between dietary models of NAFLD and vulnerability to stress-related disorders. Fifty-four male (n = 27) and female (n = 27), 14- to 18-week-old C57BL/6N mice were fed either a methionine- and choline-deficient diet (MCD) or a methionine- and choline-controlled diet (MC) and half of the total were subjected to added chronic unpredictable mild stress (CUMS) and PO. MCD caused significant weight loss, whereas MC promoted weight gain. Conductually, MCD induced anhedonia- and anxiety-like behaviors, worsened by CUMS. MC diet reduced CUMS-induced anhedonia, though anxiety-like behavior emerged only under stress. Recognition memory was impaired in stressed MCD-fed mice, while MC-fed mice showed enhanced novel object preference. At cellular level, MCD suppressed hippocampal microglia and caused cortical astrocyte dysfunction, whereas MC diet promoted cortical neurogenesis potentiated through PO, abolished by chronic stress. These findings underscore the impact of dietary composition on PO’s systemic effects under chronic stress and support a mechanistic link between NAFLD-related dysfunction and depression-like phenotypes.

Background/Objectives: This study presents the development and characterization of a novel thermoresponsive hydrogel composed of hyaluronic acid (HA), poloxamer 407, cannabidiol (CBD), and colloidal silver (Ag), designed for topical antimicrobial therapy. Methods: The Ag-CBD complex was first synthesized and subsequently incorporated into a HA–poloxamer gel matrix to produce a stable, sprayable formulation with suitable physicochemical properties for dermal applications. Results: The HA-Ag-CBD hybrid gel exhibited a physiological pH, a gelation temperature compatible with skin surface conditions, and favorable rheological behavior, including thixotropy and shear thinning—critical for uniform application and retention under dynamic conditions. Release studies confirmed a sustained delivery profile, supporting prolonged local activity of CBD and colloidal Ag. Antimicrobial assays demonstrated that the HA-Ag-CBD hybrid gel retained potent activity against Staphylococcus aureus and Candida albicans, with minimum inhibitory and bactericidal concentrations (MIC/MBC) statistically comparable to those of the unencapsulated Ag-CBD complex. Against E. coli, the HA-Ag-CBD hydrogel exhibited primarily bacteriostatic activity, with a low MIC (9.24 μg/mL) but a substantially higher MBC (387.35 μg/mL), consistent with the intrinsic structural resistance of Gram-negative bacteria. In contrast, bactericidal activity was more pronounced against Gram-positive strains, reflecting differential susceptibility related to bacterial envelope properties. CBD consistently demonstrated superior antimicrobial efficacy to colloidal Ag, while the Ag-CBD combination produced slightly enhanced, mainly additive effects, likely due to complementary membrane disruption and intracellular Ag⁺ ion activity. Cytotoxicity assays on normal human dermal fibroblasts confirmed that the HA-Ag-CBD hybrid gel maintained >70% cell viability at therapeutically relevant concentrations, in accordance with ISO 10993-5:2009 guidelines, and effectively mitigated the inherent cytotoxicity of the Ag-CBD complex. Conclusions: The HA-Ag-CBD hybrid gel demonstrates strong potential as a biocompatible, multifunctional topical formulation for the treatment of infected wounds and skin lesions. Future work will focus on in vivo evaluation, assessment of skin permeation, and further development to support translational applications.

Geranium spp. are recognized as rich sources of phenolic metabolites, with potential health benefits, yet comparative evaluations remain limited. We assessed four wild-grown Geranium spp. (G. dissectum – G1, G. lucidum – G2, G. pusillum – G3, and G. robertianum – G4), from southwestern Romanian flora, using complementary antioxidant (DPPH, ABTS and FRAP) and phytochemical (TPC and TFC) assays. Targeted UHPLC/UV–MS quantified eight phenolic acids. FRAP provided the strongest discrimination between species, and mirrored TPC, with the highest values in G4 sample. ABTS and DPPH supported the same ranking, and TFC varied only modestly, but differences were narrower and not significant between species. Caffeic acid was highest in G1 sample, and chlorogenic acid was selectively elevated in G3 sample. Gallic and protocatechuic acids were highest in G4 sample, both tracking the FRAP/TPC gradient. Syringic acid and vanillic acid were enriched in weaker-antioxidant species. Distinctive signatures included high p-coumaric acid in G4 sample and chlorogenic and ferulic acids in G3 sample. Antioxidant potential among Geranium spp. is best explained by TPC, particularly hydroxybenzoic acids, with FRAP emerging as the most sensitive discriminator. These findings provide a comparative benchmark for Geranium spp. phytochemistry and a framework for future pharmacological studies.

The latest technologies utilizing nanostructured materials with varied shapes and unique physical properties have a wide range of applications in the biomedical field, including targeted drug delivery, diagnosis, tissue regeneration, and treatment. Recent studies have concentrated on enhancing carbon nanotubes (CNTs) surfaces with metallic nanoparticles (NPs) to improve the physical properties of the hybrid material. This encompasses bolstering mechanical and thermal stability, electrical properties, bioavailability, therapeutic effects, and mitigating immune responses despite previous reports of CNTs toxicity in living organisms. Hybrid materials derived from multi-walled CNTs and silver NPs, or zinc NPs demonstrated strong antibacterial properties and could represent potential candidates against antibiotic resistance. Furthermore, nanostructures derived from CNTs and gadolinium NPs, or gold NPs display antitumoral properties and potential utility in drug delivery, medical imaging, phototherapy, and more. The functionalization of CNTs with hydrogel-type materials gives rise to a novel category of hybrid materials that may pave the way for advancements in molecular recognition, drug discovery, catalysis, and molecule-specific chemobiosensing. These new tailored scaffolds can be developed through ex situ methods, which involve preparing the inorganic component separately and then modifying the carbon surface through non-covalent or electrostatic interactions. In alternative approaches, in situ methods entail the preparation of the inorganic component in the presence of initial or functionalized CNTs. CNTs structure modification with natural polysaccharides (cellulose, chitin, alginate, chitosan, etc.) results in the development of a distinct category of biomaterials characterized by exceptional biocompatibility. These biomaterials hold significant promise for applications in tissue regeneration and medical implants.

Inonotus obliquus, a medicinal mushroom valued for its bioactive compounds, has not been previously characterized from Romanian sources. This study presents the first comprehensive chemical and biological screening of I. obliquus, introducing novel polymer-based encapsulation systems to enhance the stability and bioavailability of its bioactive constituents. Two distinct delivery systems were designed to enhance the functionality of I. obliquus extracts: (i) microencapsulation in maltodextrin (MIO) and (ii) a sequential approach involving preparation of silver nanoparticle-loaded I. obliquus (IO–AgNPs), followed by microencapsulation to yield the hybrid MIO–AgNP system. Comprehensive metabolite profiling using GC–MS and ESI–QTOF–MS revealed 142 bioactive constituents, including terpenoids, flavonoids, phenolic acids, amino acids, coumarins, styrylpyrones, fatty acids, and phytosterols. Structural integrity and successful encapsulation were confirmed by XRD, FTIR, and SEM analyses. Both IO–AgNPs and MIO–AgNPs demonstrated potent antioxidant activity, significant acetylcholinesterase inhibition, and robust antimicrobial effects against Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli. Cytotoxicity assays revealed pronounced activity against MCF-7, HCT116, and HeLa cell lines, with MIO–AgNPs exhibiting superior efficacy. The synergistic integration of maltodextrin and AgNPs enhanced compound stability and bioactivity. As the first report on Romanian I. obliquus, this study highlights its therapeutic potential and establishes polymer-based nanoencapsulation as an effective strategy for optimizing its applications in combating microbial resistance and cancer.