Search Results (287)

Advanced wound dressings should actively promote tissue repair while preventing microbial infection and excessive inflammation. In this study, multifunctional electrospun nanofibers composed of poly(vinyl alcohol)/chitosan/gelatin were developed by incorporating green-synthesized mesoporous silica nanoparticles (MSNs), Acacia gum, and Hypericum perforatum extract (HPE). Biological activity and safety were evaluated using disk-diffusion antimicrobial testing, MTT cell viability assays, nitric oxide measurement in LPS-stimulated RAW 264.7 macrophages, an L929 fibroblast scratch assay, and Ames and comet assays. The optimized nanofibers exhibited a uniform morphology with an average fiber diameter of approximately 400 nm and high encapsulation efficiencies (86–96%). MSN incorporation significantly prolonged hypericin release, producing a biphasic release profile with approximately 1.4-fold slower release than nanofibers without MSNs, while increasing Young’s modulus from 2.1 to 2.5 MPa. The hybrid nanofibers demonstrated broad-spectrum antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and Candida albicans, achieving approximately 70% of the efficacy of standard antimicrobial agents. In lipopolysaccharide-stimulated RAW 264.7 macrophages, the optimized formulation reduced nitric oxide production by approximately 51%, comparable to indomethacin and L-NAME. Although fibroblast migration was not significantly enhanced, the nanofibers exhibited acceptable cytocompatibility and showed no mutagenic or genotoxic effects in Ames and comet assays. These findings demonstrate that green-synthesized MSN-enhanced herbal nanofibers represent a safe and promising platform for sustained drug delivery and advanced wound-healing applications. Full article

Hyperforin, a polyprenylated acylphloroglucinol and major bioactive constituent of Hypericum perforatum L. (H. perforatum, St. John’s Wort), has attracted considerable interest because of its pleiotropic pharmacological properties. Although historically investigated primarily for its contribution to the antidepressant activity of H. perforatum, experimental studies have identified broader neuroprotective, anti-inflammatory, antioxidant, immunomodulatory, antimicrobial, metabolic, anticancer, and tissue-regenerative actions. However, the evidence remains heterogeneous, and an important distinction exists between findings obtained with purified hyperforin and those derived from multicomponent H. perforatum preparations. Unlike previous reviews that have primarily summarized the pharmacological activities of hyperforin, the present review adopts a translational evidence framework that distinguishes purified hyperforin from multicomponent H. perforatum preparations and evaluates the maturity of evidence from molecular mechanisms and preclinical models through pharmacokinetics, human studies, safety, and clinical development. A comprehensive narrative review was conducted according to the Scale for the Assessment of Narrative Review Articles (SANRA) recommendations. PubMed/MEDLINE, Scopus, Web of Science, Embase, and Google Scholar were searched from database inception through 25 July 2026. Mechanistic, in vitro, animal, translational, pharmacokinetic, and clinical studies, together with relevant systematic reviews and meta-analyses, were critically synthesized according to intervention type, disease-specific evidence, pharmacokinetic and formulation characteristics, safety, and translational relevance. Hyperforin acts as a pleiotropic signaling modulator affecting interconnected pathways involved in neurotransmission and neuroplasticity, inflammatory and redox regulation, mitochondrial and cellular homeostasis, immune function, and metabolism. Extensive cellular and animal evidence supports biological activity across neuropsychiatric, neurodegenerative, inflammatory, immune-mediated, cardiometabolic, oncological, gastrointestinal, infectious, dermatological, and other chronic disease settings. Nevertheless, evidence maturity differs markedly among indications. The strongest human evidence concerns standardized hyperforin-containing H. perforatum preparations for mild-to-moderate depression, whereas most other applications remain preliminary or predominantly preclinical. Adequately powered randomized controlled trials of purified hyperforin are lacking, preventing attribution of the clinical effects of H. perforatum preparations specifically to hyperforin. Translation is further constrained by poor aqueous solubility, chemical instability, variable bioavailability and formulation composition, limited compound-specific pharmacokinetic data, and clinically important herb–drug interactions, particularly through PXR-mediated induction of CYP3A4 and P-glycoprotein. Hyperforin is a pharmacologically promising multifunctional natural compound, but its experimental activity currently exceeds the strength of compound-specific clinical evidence. Future research should prioritize chemically defined and preferably purified formulations, rigorous pharmacokinetic and dose-finding studies, biomarker-supported target-engagement assessment, and adequately powered randomized controlled trials, together with long-term safety, interaction, standardization, and regulatory evaluation. Demonstrating predictable human exposure, biologically relevant target engagement, clinically meaningful efficacy, and an acceptable long-term safety profile will be essential for determining whether hyperforin can progress from experimental promise to evidence-based therapeutic application. Full article

Standard pharmacotherapy for mental disorders, including depression and anxiety, is supported by extensive clinical validation and international treatment guidelines. However, it is frequently associated with limitations such as adverse side effects, low patient adherence, and the risk of relapse. Conventional approaches rely primarily on antidepressants, anxiolytics, mood stabilizers, neuroleptics, and stimulants, which modulate monoaminergic, GABAergic, and dopaminergic neurotransmission. Recently, preclinical and emerging clinical studies have suggested that selected natural substances—specifically mushroom-derived compounds and well-established medicinal plants—may offer complementary therapeutic pathways. This narrative review critically evaluates the pharmacological efficacy, mechanisms of action, and safety profiles of selected natural compounds, including psilocybin-related tryptamines, Hericium erinaceus, ibotenic acid/muscimol from Amanita muscaria, ergothioneine, as well as notable botanical agents (e.g., Hypericum perforatum, Valeriana officinalis). We systematically distinguish between robust human clinical data (e.g., psilocybin-assisted therapy) and preliminary in vitro/in vivo findings. Particular attention is paid to their neurotrophic, anti-inflammatory, and neuromodulatory properties, while emphasizing substantial safety concerns, including intoxication risks associated with isoxazole derivatives, and potentially severe cytochrome P450-mediated drug–drug interactions. Ultimately, while certain natural compounds show promise as adjunctive interventions, most remain strictly investigational and cannot replace evidence-based conventional pharmacotherapy without further long-term, large-scale randomized controlled trials. Full article

Three previously undescribed phenolic dimers, including a pair of enantiomeric stilbene dimers (1a/1b) and one optically pure stilbene dimer (2), were separated from the fruits of the Miao medicine Hypericum patulum Thunb. Structural clarification and assignment of absolute configurations were achieved through 1D/2D NMR spectroscopy, optical rotation measurements, and analysis of experimental electronic circular dichroism (ECD) spectra. Their antioxidant and anti-α-glucosidase activities were evaluated. The new stilbene dimers exhibited potent antioxidant activity in both DPPH and ABTS free radical scavenging assays. Moreover, (−)-caesalstilbene C (1b) demonstrated the highest anti-DPPH and anti-ABTS activities among all isolated compounds. Compounds 1–2 also showed significant α-glucosidase-inhibitory activity, comparable to the positive control acarbose. These findings provide a foundation for developing novel antioxidants or α-glucosidase inhibitors as lead compounds in the search for new antidiabetic agents. Full article

Quantitative flowering phenotypes are needed to support breeding and harvest management in Hypericum perforatum L. (St. John’s wort), but manual flower assessment is slow and difficult to standardize under field conditions. UAV-Hyp is a multi-temporal UAV RGB dataset containing 12,653 high-resolution images acquired at 26 measurement dates across the complete flowering period of 15 H. perforatum accessions. The images represent variable illumination, soil moisture, weed pressure, and developmental stages. The dataset provides 59,163 plant bounding boxes and 107,054 flower bounding boxes. As an application example, cascaded YOLOv8 plant and flower detectors achieved mAP@0.50:0.95 values of 0.977 and 0.950, respectively. UAV-Hyp supports scalable flower quantification and the development of time-series phenotyping methods for genotype comparison and quality-oriented medicinal-plant breeding. Full article

Hypericum perforatum L. olive-oil macerate is a traditional topical remedy whose wound-healing efficacy is well documented, yet the phytochemical and mechanistic basis of its cosmetic-relevant activity remains poorly defined. This study provides an integrated experimental and in silico characterization of a traditionally prepared macerate of defined origin. The fatty acid composition, oxidative-stability indices, total phenolic and flavonoid contents, naphthodianthrone level, antioxidant capacity, and tyrosinase inhibition were determined, and the principal constituents were examined by molecular docking and in silico skin-permeation and toxicity profiling. The olive-oil matrix was oleic acid-dominated (73.9%) and oxidatively stable (iodine value 86.0; oxidizability index, COX, 1.84), while the macerate showed modest phenolic ($36.84 \mathsf{\mu }$g pyrocatechol equivalents, PCE/mg) and naphthodianthrone (0.044 mg/mL hypericin equivalents) contents. It showed limited antioxidant activity but moderate tyrosinase inhibition (38.75% at $200 \mathsf{\mu }$g/mL). Docking revealed that, despite high affinity scores, the naphthodianthrones lay 7–9 Å from the catalytic copper centre (an artefact of the scoring function), whereas fatty acids accessed the active site more closely, implicating the matrix in the observed activity. In silico profiling indicated that the photoactive naphthodianthrones are largely retained at the skin surface. These findings link this centuries-old preparation to a mechanistically informed understanding of its cosmetic potential. Full article

This study aimed to characterize the metabolomic profile of aqueous extracts of Hypericum perforatum (St. John’s wort) commercial samples using ¹H NMR spectroscopy, in order to evaluate their chemical composition as consumed in infusion form. Seven retail samples were extracted with water under conditions simulating tea preparation and analyzed using ¹H NMR. Metabolite identification and quantification were performed with Chenomx^® software, followed by multivariate statistical analyses including PCA and OPLS-DA. A total of 37 metabolites were identified, predominantly primary metabolites such as sugars (glucose, fructose), amino acids (glycine, asparagine), short-chain organic acids (malic, citric, and acetic acids), secondary metabolites (trigonelline, chlorogenic acid) and metabolism products (methanol, ethanol, acetic acid and acetone). Notably, key bioactive compounds traditionally associated with H. perforatum, such as hypericin and hyperforin, were not detected under the experimental conditions employed. Multivariate analyses revealed significant variability among samples, suggesting differences in composition likely related to origin, processing, or potential adulteration. These findings demonstrate that aqueous preparations of St. John’s wort differ substantially from extracts used in clinical trials, being dominated by primary metabolism rather than specialized bioactive compounds. This has important implications for the interpretation of its therapeutic effects when consumed as tea. Furthermore, the study highlights the utility of NMR-based metabolomics as a robust tool for quality assessment and authentication of herbal products. Full article

Background/Objectives: Hypericum perforatum L. is a medicinal plant containing diverse specialized metabolites, including flavonoids, naphthodianthrones, phloroglucinols, and phenolic acids. However, the relationship between its quantitative flavonoid composition and extract-level anti-inflammatory activity remains insufficiently characterized. This study aimed to profile the chemical constituents of H. perforatum extract (HPE), quantify selected flavonoid markers, and relate these data to nitric oxide (NO) inhibitory activity in LPS-stimulated RAW 264.7 macrophages. Methods: HPE was chemically characterized by LC–MS/MS, and selected flavonoid constituents were quantified using HPLC/PDA analysis. Cell viability and NO production were evaluated in RAW 264.7 macrophages using MTT and Griess assays, respectively. Results: LC–MS/MS profiling tentatively identified 36 compounds in HPE, with flavonoid-related metabolites representing the largest portion of the annotation list. Multiple quercetin-derived glycosides and conjugates were detected, indicating a flavonoid-rich phenolic profile. HPLC/PDA analysis showed that hyperoside (2) was the most abundant quantified marker at 12.44 mg/g extract, followed by rutin (1, 9.18 mg/g), quercetin (4, 6.64 mg/g), and avicularin (3, 5.55 mg/g), whereas amentoflavone (5) was detected only at trace level. At non-cytotoxic concentrations, HPE significantly suppressed LPS-induced NO production, iNOS protein expression, and the mRNA expression of the pro-inflammatory cytokines Tnf and Il6 in RAW 264.7 macrophages. Compounds 1–4 also reduced NO production and iNOS protein expression, although their effects on cytokine mRNA expression differed among compounds. Conclusions: HPE exhibited anti-inflammatory potential in LPS-stimulated macrophages, as shown by inhibition of NO production, downregulation of iNOS protein expression, and reduced Tnf/Il6 mRNA expression. However, extract-equivalent comparison indicated that the extract-level response could not be directly assigned to any single quantified flavonoid marker. The broader flavonoid-rich phenolic matrix may provide a plausible context for this response, but additive or synergistic interactions among constituents were not directly demonstrated and require further validation. Full article

Lung cancer represents a substantial global oncology burden, exhibiting mortality rates that surpass those of prostate, pancreatic, and breast cancers. Extensive research has established a correlation between exposure to polycyclic aromatic hydrocarbon mixtures—particularly those containing benzo(a)pyrene (BaP)—and elevated risks of pulmonary and dermal malignancies across various species, including humans. Hesperidin (HSP), a prominent bioactive flavonoid found in citrus fruits and medicinal herbs such as Hypericum perforatum, is recognized for its diverse pharmacological properties. The present study aimed to elucidate the antioxidant and anti-inflammatory efficacy of HSP against BaP-induced toxicity in the A549 non-small cell lung cancer (NSCLC) cell line. Following the determination of application concentrations via MTT assay, the modulatory effects of HSP on cellular proliferation, oxidative stress markers (TAS, TOS, and OSI), and key pro-inflammatory cytokines (TNF−α, IL−1β, and TGF−β) were systematically evaluated. Isolated exposure to BaP predominantly triggered a targeted upregulation of IL-1β; however, hesperidin demonstrated unexpected pro-oxidant dynamics, characterized by a substantial drop in TAS alongside a concurrent elevation in both TOS and OSI profiles, especially at maximum-dose concentrations. Notably, combining BaP with this heightened hesperidin regimen manifested the most severe oxidative distress phenotype, implying a synergistic pro-oxidant cascade between the two agents. On the contrary, minimized concentrations of hesperidin exerted explicit cytoprotective mitigation against the BaP-induced surge in IL-1β, thereby confirming a highly delicate and narrow therapeutic index for this flavonoid. Full article

Climate change and population growth are intensifying global food security challenges by reducing agricultural productivity and increasing reliance on fertilizers. In this context, developing sustainable and economically efficient agricultural solutions becomes essential. The study presents the synthesis of an interpenetrating polymer network (IPN) of hydrogels by combining bacterial cellulose (BC) with poly(acrylic acid) crosslinked with N, N-methylene-bis-acrylamide (PAA–co–MBA) via free radical copolymerization. To explore their potential as bioactive compound carriers, an ethanolic hydroalcoholic phytoextract (EHP) obtained from Hypericum perforatum L. and Melissa officinalis L. was directly encapsulated within the IPN hydrogels. The EHP is valued for its rich bioactive profile and antifungal, antimycobacterial, and antioxidant properties. The results of rheology measurements and thermal gravimetric analysis (TGA) revealed that incorporating BC into the IPN hydrogels significantly enhanced the mechanical stiffness, thermal resistance, and overall stability of the resulting IPN structures. Fourier Transform Infrared (FTIR) spectroscopy and Scanning Electron Microscopy (SEM) confirmed the structural organization and the porosity of the developed composite, as well as the successful fabrication of IPN hydrogels in the EHP medium. Under optimal conditions, the IPN hydrogels exhibited a reduced swelling capacity, thereby slowing the diffusion of the bioactive agents, reducing the application frequency, and enhancing the utilization efficiency. Taken together with the controlled-release performance, these findings demonstrate the potential of BC (PAA-co-MBA) IPN hydrogels as biodegradable and sustainable carrier systems for controlled delivery applications and suggest that they may be promising candidates for hydrogel-based agricultural delivery systems. Full article

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. Full article

Hypericin (Hyp) is a naturally occurring photosensitizer (PS) exhibiting a broad spectrum of biological activities. However, its high hydrophobicity significantly limits its medical applicability. This study aimed to develop an efficient method for extracting Hyp from Hypericum perforatum L. biomass and to obtain its water-soluble micellar formulation. A protocol for Hyp isolation from the aerial parts of the plant was established, involving a preliminary defatting step using a Soxhlet apparatus, followed by ultrasonic-assisted extraction with acetone. The water-soluble formulation was prepared via the thin-film hydration method using the nonionic block copolymer Pluronic F-127. The resulting micelles demonstrated colloidal stability, with a mean hydrodynamic diameter of approximately 30 nm. A high Hyp loading efficiency was achieved, with an encapsulation efficiency (EE) of 95.4 ± 2.7%, yielding a concentration of 600.6 ± 16.6 µM within the micellar formulation. In vitro biological studies were performed using the murine GL261 glioblastoma cell line. The micellar Hyp formulation exhibited efficient time-dependent cellular accumulation and photoinduced cytotoxicity, with no observable dark toxicity. The proposed method enables the production of a stable Hyp formulation that retains its photosensitizing properties, thereby opening promising avenues for its application in photodynamic and sonodynamic therapies. Full article

Background/Objectives: Hypericum perforatum L. (St. John’s Wort) is extensively utilized in ethnopharmacology due to its anti-inflammatory and immunomodulatory properties. However, its effects on the interaction between innate immunity and oxidative homeostasis remain incompletely characterized, particularly in alternative invertebrate models. This study aimed to evaluate the effects of H. perforatum extract on oxidative homeostasis and protein metabolism using the Galleria mellonella model, a 3R-compliant and ethically sustainable platform for preliminary immunological and redox-related screening. Methods: Last instar G. mellonella larvae were administered increasing concentrations of H. perforatum extract (0.001–20 mg mL⁻¹) by intrahemocoelic injection. After 24 h, hemolymph samples were analyzed for total protein (TP), total hemocyte count (THC), encapsulation and melanization responses, superoxide dismutase (SOD) activity, catalase (CAT) activity, and malondialdehyde (MDA) levels. The phytochemical profile of the extract was additionally evaluated using GC–MS analysis. Results: Significant group-dependent alterations were observed in TP levels and THC values, with the HP-2 group demonstrating the highest hemocyte counts and enhanced strong encapsulation responses. Higher extract concentrations, particularly HP-4, were associated with increased weak encapsulation profiles, suggesting altered cellular immune organization. Melanization responses became significantly elevated at 24 h following treatment. In contrast, SOD activity, CAT activity, and MDA levels did not differ significantly among groups, indicating preservation of oxidative homeostasis under the tested conditions. Conclusions: H. perforatum extract induced dose-dependent modulation of cellular and humoral immune responses in G. mellonella without evidence of detectable oxidative disruption during acute exposure. These findings support the utility of the G. mellonella model for preliminary evaluation of botanical immunomodulators and suggest that H. perforatum may influence immunophysiological pathways independently of overt oxidative toxicity. Full article

Background: Sleep disorders, particularly insomnia, represent a major public health concern, while currently available hypnotic drugs are often limited by adverse effects and poor long-term tolerability. Methods: In this study, we investigated the sleep-promoting effects of a mixture of Hypericum perforatum L. and Melissa officinalis L. extract (HME) and its underlying mechanisms in male ICR and C57BL/6 mice. In a pentobarbital-induced sleep model in mice, sleep onset latency and total sleep time were measured. Pharmacological studies using various antagonists and agonists were conducted to elucidate receptor-mediated mechanisms. Immunohistochemical and immunofluorescence analyses were performed to assess neuronal activity, and cortical mRNA expression was evaluated by quantitative analysis. HPLC analysis was used to identify the major constituents of HME, and their pharmacological profiles were functionally evaluated. Results: HME significantly reduced sleep onset latency and prolonged total sleep time. These hypnotic effects were shown to be mediated through adenosine and melatonin receptor signaling pathways. Immunohistochemical and immunofluorescence analyses showed that HME suppressed neuronal activity in wake-promoting cholinergic and orexinergic neurons of the basal forebrain and lateral hypothalamus, while enhancing activation of sleep-promoting GABAergic neurons in the ventrolateral preoptic nucleus. At the molecular level, HME increased cortical mRNA expression levels of adenosine A₁ receptor, adenosine A_2A receptor, melatonin receptor 1, and melatonin receptor 2. From the HPLC analysis, rosmarinic acid and hyperoside were identified as the major constituents of HME. Functional evaluation of these compounds revealed complementary pharmacological profiles, with hyperoside primarily acting through adenosine receptors and rosmarinic acid engaging both adenosine and melatonin receptor pathways. Conclusions: These findings suggest that HME enhances both sleep initiation and maintenance through adenosine and melatonin receptor signaling pathways, thereby supporting its potential as a multitarget therapeutic agent for improving sleep quality. Full article

Hypericum species are known for their phytochemical richness and diverse pharmacological activities; however, the biological potential and underlying mechanisms of Hypericum triquetrifolium remain unclear. This study aimed to investigate the phytochemical profile and bioactivities of Hypericum triquetrifolium hydroalcoholic extract (HTE). Plant samples collected from Gelibolu (Çanakkale, Türkiye) were analyzed by HPTLC, revealing the presence of rutin, hyperoside, chlorogenic acid, neochlorogenic acid, and hypericin. Antioxidant activity was evaluated using DPPH, CUPRAC, and FRAP assays, demonstrating strong activity across all tests. Anti-inflammatory effects were assessed in LPS-stimulated RAW264.7 macrophages. HTE significantly reduced nitrite, PGE₂, IL-6, ROS, and MDA levels, with the most pronounced effect observed at 0.5 mg/mL (p < 0.05). Cytotoxic and anticancer activities were evaluated in MIA PaCa-2 pancreatic cancer cells and healthy human dermal fibroblasts. The extract exhibited selective cytotoxicity toward cancer cells (IC₅₀ = 0.16 mg/mL), with approximately fivefold lower toxicity in healthy cells. Cell cycle analysis demonstrated G0/G1 arrest, while the Annexin V assay revealed dose-dependent apoptosis (p < 0.0001). DNA damage analysis further supported its anticancer potential. Overall, HTE exhibits potent antioxidant, anti-inflammatory, and selective anticancer activities by reducing oxidative stress, inducing cell cycle arrest, and promoting apoptosis, highlighting its potential as a therapeutic agent. Full article