The side effects associated with commonly used hypoglycemic drugs have spurred the search for effective plant-based remedies for the prevention and treatment of diabetes. This review aims to summarize and systematize available data on the major classes of plant metabolites with antidiabetic properties, the intracellular mechanisms underlying their action, and plant species showing potential antidiabetic activity. We performed a systematic review of 260 studies identified in PubMed, ScienceDirect, and Web of Science, following the PRISMA 2020 guidelines. Numerous classes of plant secondary metabolites, including terpenoids, alkaloids, flavonoids, curcuminoids, stilbenes, phenolic acids, and phenylpropanoids, hold great promise for the prevention of type 2 diabetes. These compounds influence multiple metabolic pathways by inhibiting carbohydrate-metabolizing enzymes, neutralizing reactive oxygen species, reducing blood glucose and pro-inflammatory cytokine levels, increasing intracellular glutathione levels, and protecting pancreatic β-cells from apoptosis. Metabolites with antidiabetic activity can be isolated from plants of various families, such as Asteraceae, Rutaceae, Zingiberaceae, Costaceae, Moraceae, Rosaceae, and Vitaceae. Accordingly, this review proposes candidate plants growing in the Russian Federation (Betula pendula, Quercus spp., Silybum marianum, Hypericum perforatum, Bidens tripartita, Urtica dioica, Taraxacum officinale) as sources of bioactive compounds for the development of drugs to treat type 2 diabetes. The review emphasizes that, despite the potential of plant metabolites to prevent carbohydrate metabolism disorders, several issues remain unresolved, including low solubility and bioavailability, physiological instability, and the lack of standardized plant raw materials and extracts, which is critical for achieving therapeutic effects. Further large-scale in vivo studies are needed to assess the side effects and potential interactions of plant metabolites with conventional drug components. Plant metabolites have demonstrated hypoglycemic and antioxidant effects for the development of antidiabetic drugs, but achieving sustainable results requires addressing key limitations. This review may be useful for research groups and specialists involved in the development and testing of phytochemical platforms, including those with antidiabetic applications.

Hypericum perforatum L. and Glycyrrhiza glabra L. preserve cardiac mitochondrial redox homeostasis in E2 deficiency via ERβ-MAO-A modulation.

A randomized, controlled, experimental animal study. This study investigates the influence ofHypericum perforatum (St. John's Wort) and its active compound, hypericin, influence on oxidative stress markers and neurotrophic factor expression during the acute phase of SCI in male rats. University animal research facility equipped with dedicated surgical suites for SCI induction and controlled-environment housing for rodents. SCI was induced in Wistar rats through a contusion injury model. The treatment groups received either hypericin (50/100 mg/kg, i.p.) or Hypericum perforatum extract (50/100 mg/kg, i.p.) for two weeks. Motor function was evaluated with the Basso, Beattie, and Bresnahan (BBB) test, and nociceptive sensitivity was assessed using the tail flick test. Serum levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), nitric oxide (NO), and reactive oxygen species (ROS) were measured. Histological analysis of myelination was conducted using Luxol fast blue staining. SCI led to a significant decline in BBB scores, an increase in oxidative stress markers (NO, ROS), and a reduction in BDNF levels. Treatment with 100 mg/kg hypericin notably improved BBB scores (p < 0.00001), reduced NO and ROS levels (p < 0.0001), and increased BDNF expression compared to untreated SCI rats. Histological examination showed less demyelination in the treated groups, with hypericin demonstrating more pronounced effects than Hypericum perforatum extract. Hypericin exhibited strong neuroprotective properties by reducing oxidative stress, enhancing neurotrophic factor expression, and preserving myelin integrity. These findings highlight its potential as a therapeutic agent for reducing secondary damage following SCI.

Drought stress represents a major abiotic factor responsible for reducing the growth, yield and quality of important plants. This research was investigated the potential of ZnO Nano particles (ZnO NPs) to alleviate drought stress in Hypericum perforatum (common St. John's Wort). A factorial experiment using randomized complete block design (RCBD) was performed with 3 replications and 4 different irrigation treatments (100%, 70%, 40%, and 25% of field capacity) combined with 4 different concentrations of ZnO NPs (0, 10, 50, and 100 mg L- 1). Drought stress had a significant negative impact on different morphophysiological characteristics, including plant height, root length, leaf area, chlorophyll concentration, relative water content, and photosynthetic efficiency (Fv/Fm). Additionally, drought stressed plants exhibited significantly higher activity of catalase (CAT) and peroxidase (POD), proline content, total phenolic content, content of essential oils, and accumulation of hypericin than non-stressed plants. These biochemical adjustments indicate the activation of osmotic regulation and antioxidant defense mechanisms that contribute to drought stress tolerance. The application of ZnO NPs via foliar application reduced the adverse effects of drought and significantly improved growth characteristics, levels of photosynthetic pigments, and plant water status under drought conditions. Moreover, in combination with the application of ZnO NPs (especially at concentrations of 50 and 100mg L⁻¹), moderate drought stress (40-70% FC) resulted in significantly higher essential oils and hypericin accumulation compared to all other treatments. Principal component and correlation analysis confirmed the relationships between physiological performance and stress-related metabolites. Overall, application of ZnO NPs represent an innovative opportunity for mitigating drought related stress in H. perforatum.

Hypericum perforatum L.: A legacy of herbal medicine in light of modern scientific evidence.

Depression is a prevalent and disabling mental disorder associated with increased suicide risk and impaired quality of life. Herbal medicines such as Hypericum perforatum L. (St. John's Wort [SJW]) and Chaihu Shugan San (CSGS) have been widely used to treat depressive symptoms, yet their system-level molecular mechanisms remain incompletely understood. In this study, we applied a multi-omics strategy centered on quantitative proteomics, combined with metabolomics and microbiota profiling, to investigate the antidepressant mechanisms of CSGS and SJW in a chronic unpredictable mild stress rat model. Behavioral assessments confirmed that both treatments significantly alleviated depressive-like behaviors. Proteomic analysis identified 204 differentially expressed proteins (DEPs) in the CSGS group and 473 DEPs in the SJW group. Functional enrichment analyses suggested that CSGS was more closely associated with lipid metabolism, whereas SJW was linked to broader metabolic processes. Integrative metabolomic and microbiota analyses further supported these proteomics-driven pathway distinctions, with SJW showing stronger associations with gut microbiota alterations. CSGS and SJW alleviated depressive-like behaviors through divergent yet partially overlapping molecular mechanisms. These findings highlight the utility of multi-omics approaches for elucidating system-level mechanisms of complex herbal medicines.

Depression and anxiety are common during pregnancy, but the prevalence of antidepressant use during pregnancy in Switzerland is not well documented. We explored antidepressant use before, during, and after pregnancy in Switzerland. We conducted a descriptive study using a Swiss health care insurance claims database (Helsana) between 2015 and 2021. We included pregnancies resulting in birth of women who were continuously insured during three 270-day periods: preconceptional, pregnancy, and postpartum. In these periods, we quantified the exposure prevalence to antidepressants overall and stratified by region and use of co-medication. Antidepressants of interest included selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors, Hyperici herba and others. Additionally, we assessed prevalence of antidepressant discontinuation during pregnancy. We included 34,584 pregnancies of whom 1386 (4.0%) were exposed (≥1 claim) to antidepressants preconceptionally, 788 (2.3%) during pregnancy, and 1273 (3.7%) postpartum. Of 1386 women with preconceptional use, 60% had no antidepressant claim during pregnancy. Antidepressant use decreased from 1.6% in trimester one to 1.1% in trimester three. The most frequently dispensed antidepressants during pregnancy were SSRIs (75.0%). Exposure to antidepressants was two-fold higher in the French-speaking region (2.6%) than in Central Switzerland (1.3%). About one-third of women continuing antidepressant treatment during pregnancy also used benzodiazepines (co-medication) at least once during this time. 4 of 100 women in Switzerland took antidepressants before pregnancy, but 60% discontinued treatment when they became pregnant. Since untreated depression in pregnancy may lead to severe long-term consequences for mother and child, this might be of concern.

A multi-omics comparison unveils convergent and divergent antidepressant mechanisms of fluoxetine and St. John's wort extract.

This study investigates physicochemical, mechanical, and thermal effects of St. John’s wort (JW) oil on gelatin-based films for potential biomedical applications as there is limited research on gelatin biomaterials containing JW oil as sole bioactive component. Transparent films were fabricated at gelatin:JW oil ratios of 20:0, 20:1, 20:5 (w/w) designated as JW-0, JW-1, JW-2, respectively, via solution casting. Gas chromatography revealed that JW oil is rich in unsaturated fatty acids, predominantly linoleic and oleic acids, while FTIR confirmed their successful integration into the gelatin matrix through the fatty acid peak at 1743 cm−1. Oil droplets, increasing with oil content was shown by SEM. JW oil improved water durability by reducing water aging by up to 8%. JW oil acted as a plasticizer, raising elongation at break (EAB) from 188% in JW-0 to 231% and 209% in JW-1 and JW-2, respectively. DSC indicated a higher Tmax in JW-1 (116 °C) compared to JW-2 (110 °C), evidencing better thermal stability. In conclusion, JW oil can be effectively incorporated into gelatin as a single active component. Specifically, JW-1 formulation achieved an optimal balance between mechanical and structural integrity, flexibility, and thermal stability, underscoring its potential as a cost-effective, bioactive wound dressing material.

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 A2A 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.

This study aims to chemically characterize a traditionally prepared Hypericumperforatumolive oil macerate and to evaluate its cosmetic-relevant bioactivities. The macerate was prepared using fresh flowering aerial parts infused in olive oil under traditional sunlight conditions (Bulut et al., 2017). Fatty acid composition was determined by GC–FID/MS, while total phenolic and flavonoid contents and naphthodianthrone levels were analyzed using spectrophotometric methods. Antioxidant capacity and tyrosinase inhibitory activity were evaluated by in vitro assays. The results showed that the lipid matrix was dominated by oleic acid (73.92%), followed by palmitic and linoleic acids, confirming a monounsaturated fatty acid–rich profile. The macerate contained measurable amounts of phenolic (36.84 ?g PCE/mg) and flavonoid compounds (35.49 ?g QE/mg), along with naphthodianthrones (0.044 mg/mL, expressed as hypericin equivalents). In antioxidant assays, the macerate exhibited reducing capacity in the CUPRAC assay, whereas no significant radical scavenging activity was observed in DPPH and ABTS systems. In contrast, moderate tyrosinase inhibition (38.75% at 200 ?g/mL) was detected. These findings indicate that the traditional maceration process enables the transfer of plant-derived bioactive compounds into an olive oil matrix, providing a chemically characterized system with potential relevance for dermocosmetic applications.

Wound and device-associated infections caused by drug-resistant microorganisms are a major global health problem, increasing morbidity, mortality and economic burden. Antimicrobial nanofibrous scaffolds have therefore gained attention as wound dressings capable of reducing infection risk. In this study, gelatin/chitosan (GEL/CTS) nanofibrous scaffolds incorporating silver–iron bimetallic nanoparticles (Ag–FeNPs) synthesized via a green route using Hypericum perforatum (H. perforatum) leaf extract were developed as potential antibacterial wound-dressing materials. Ag–FeNPs were produced at room temperature and characterized by different analytical techniques. Microstructural analysis confirmed that the biogenic nanoparticles were spherical, with an average size of 60.98 ± 18.09 nm, and were uniformly distributed throughout the GEL/CTS fibers. Ag–FeNPs with varying Ag : Fe ratios were subsequently embedded into the polymeric matrix to enhance scaffold wettability and antibacterial performance. FT-IR, XRD, FE-SEM, and water-contact-angle measurements demonstrated that incorporation of CTS and Ag–FeNPs reduced the fiber diameter (171.47 ± 55.96 nm) and improved hydrophilicity, with the GEL/CTS/Ag–Fe (2 : 1) formulation exhibiting the lowest WCA value (60.72°). Antibacterial assays conducted against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) revealed that the green-synthesized Ag–FeNPs were active against both strains, with stronger inhibition observed for E. coli. Among the nanofibrous scaffolds, the sample containing the highest Ag composition yielded the most pronounced reduction in bacterial colony formation. Overall, these findings indicate that GEL/CTS scaffolds reinforced with Ag–FeNPs possess favorable structural and biological properties, which highlighting their potential as effective antibacterial materials for applications such as wound dressings.

Wound-associated infections persist as a major global health concern, particularly in the context of increasing antimicrobial resistance and reduced efficacy of conventional therapies. Essential oils (EOs) obtained from medicinal plants represent promising alternatives due to their antimicrobial and wound-healing properties. This study evaluated the chemical composition, antimicrobial activity, and interaction effects of Hypericum perforatum (HP) and Achillea millefolium (AM) EOs, tested individually and in fixed-ratio combinations. Chemical profiling by GC–MS revealed that HP EO is dominated by caryophyllene (20.74%) and β-thujone (18.47%), while AM EO is characterized by aromadendrene (19.12%), caryophyllene (12.97%), and chamazulene (10.13%). Antimicrobial activity was assessed against wound-associated microorganisms using MIC and MBC/MFC assays, and interactions were assessed by the fractional inhibitory concentration index (FICI) and heatmap analysis. The results displayed higher susceptibility of Gram-positive bacteria, particularly Staphylococcus epidermidis, with MIC values as low as 0.56 µL/mL in EO combinations. Synergistic effects were observed exclusively for S. epidermidis in mixtures enriched in HP EO (60:40 and 70:30; FICI = 0.34), while Gram-negative bacteria and Candida albicans exhibited predominantly indifferent responses. These findings indicate that optimized EO combinations may enhance antimicrobial efficacy and support their potential application in wound management.

A GATA transcription factor modulates melatonin production and drought resistance in Hypericum perforatum.

HMPs derived from Hypericum perforatum, herba (St.John's wort) play an important role in treating mild to moderate depressive episodes and mental exhaustion, for example. The genotoxic safety of these HMPs has already been assessed and reviewed in recent years. However, further data on the genotoxic potential of Hypericum perforatum, herba preparations would allow the evaluation of the therapeutic safety of the herbal drug and preparations thereof in accordance with the genotoxicity guideline of the HMPC of the EMA. Accordingly, their genotoxic potential was tested using the "bracketing and matrixing" concept, whereby extracts are tested at and between the extremes of their extraction solvents (ranging in strength from polar to non-polar) to cover the entire spectrum of the drug's constituents. In the present study, five dry extracts of Hypericum perforatum, herba, representing the full range of potential extraction solvent polarities (water, ethanol 50% (v/v), methanol 80% (v/v), ethanol 80% (v/v), and n-heptane) were tested using the Ames test, according to the OECD and HMPC guidelines. No mutagenic effects were observed for any of the five test strains in two independent experiments (plate incorporation test and pre-incubation test) each carried out with and without metabolic activation, even at the highest concentrations (5000 µg/plate), in accordance with the OECD guideline No. 471.

Hexavalent chromium, a widespread heavy metal, induces apoptosis via the mitochondrial pathway through Bax (pro-apoptotic) and Bcl2 (anti-apoptotic) proteins. Hypericum perforatum, rich in antioxidants, can neutralise free radicals. This study investigated the effects of CrVI on the pancreas and the protective role of Hypericum perforatum. Five groups of animals were used: control, Cr (CrVI for 3 months), CrH (CrVI + 2.5% Hypericum perforatum extract made from flowers, for 3 months), Cr2 (CrVI for 3 months + distilled water for 1 month), and CrH2 (CrVI for 3 months + Hypericum perforatum extract for 1 month). Samples were collected for histological analysis, gene expression (qRT-PCR), and blood glucose level analysis. CrVI exposure (Cr, Cr2) caused pancreatic damage: oedema, reduced islet size, endocrine cell vacuolisation, and endothelial swelling. Lesions were milder in CrH, while CrH2 resembled the control group. The Bax/Bcl2 ratio increased under CrVI (highest in Cr2), indicating apoptosis, but decreased toward control values in CrH and CrH2. Blood glucose levels confirmed these findings. CrVI proved toxic to the endocrine pancreas, inducing structural and molecular alterations that impaired carbohydrate metabolism. Administration of Hypericum perforatum extract reduced these effects, confirming its antioxidant action and potential as a protective agent against CrVI-induced oxidative stress.

Background: Oral biofilms are a major etiological factor in dental caries, periodontal disease, peri-implantitis, and endodontic infections. Increasing antimicrobial resistance and the limitations of conventional therapies have intensified interest in antimicrobial photodynamic therapy (aPDT). Hypericin, a natural photosensitizer derived from Hypericum perforatum, demonstrates potent reactive oxygen species generation and broad antimicrobial activity; however, its dental applications remain insufficiently synthesized. Objective: To systematically evaluate the antimicrobial efficacy, treatment parameters, safety, and clinical potential of hypericin-mediated aPDT against oral biofilms and infections in dentistry. Methods: This systematic review was conducted according to PRISMA 2020 and registered in PROSPERO CRD42024617727. Electronic searches of PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library (January 2010 to December 2025) were performed. Studies assessing hypericin-mediated aPDT in oral or dental contexts were included. Methodological quality was evaluated using a predefined nine-domain risk-of-bias tool. Results: Eleven studies met the inclusion criteria. Hypericin-mediated aPDT demonstrated strong antimicrobial effects, achieving up to 99% planktonic inactivation and significant biofilm reduction across bacterial and fungal species. Activity was particularly pronounced against Gram-positive organisms, including Staphylococcus aureus and Enterococcus faecalis. However, efficacy against mature biofilms was variable and often dependent on formulation and irradiation parameters. Most studies showed moderate methodological quality, with frequent deficiencies in reporting light calibration and dosimetry. Advanced delivery systems, including liposomal and nanoparticle formulations, improved photodynamic performance. Conclusions: Hypericin-mediated aPDT shows promising antimicrobial activity against oral pathogens and biofilms, with favorable selectivity and safety profiles. Nevertheless, the evidence remains predominantly preclinical and heterogeneous. Standardized protocols and well-designed clinical trials are required before routine dental implementation can be recommended.

ABSTRACT In the present investigation, biocomposites were created by inserting the biomass of Hypericum perforatum (HP), which is regarded as a material that generates zero waste, into a biopolymer composed of sodium alginate (SA) at weight ratios of 10%, 20%, and 30%. Using Fourier transform infrared–attenuated total reflectance (FTIR‑ATR) spectroscopy, scanning electron microscopy (SEM), energy dispersive X‐ray spectroscopy (EDX), and X‐ray diffraction (XRD) studies, the biocomposites that were produced were analyzed and described. Inverse gas chromatography (IGC) was used to explore the surface properties of these materials throughout a temperature range of 303.2–328.2 K. The Dorris–Gray, Donnet–Park, Schultz, and Hamieh methods were utilized in this investigation. The determination of the specific adsorption enthalpy, the specific adsorption free energy, and the acid–base constants for both HP and the SA/HP composites was made possible using experiments that were carried out at an infinite dilution. Additionally, the selectivity coefficients (α) of structural isomers were determined at infinite dilution for a variety of acetate and alcohol isomers within the same temperature range. This was accomplished by employing the IGC technique.

Silver-doped MoOx NPs with phytochemicals for photodynamic therapy application: Playing with the sequence of surface modification steps.

Integrated dual-split high capacity sorptive extraction and chemometrics reveal extraction-dependent volatile signatures in Hypericum perforatum