The issue of soil contamination by heavy metals is widely acknowledged. Some plants, including medicinal species like St. John\'s wort (Hypericum perforatum L.), exhibit accumulation traits, allowing them to accumulate elevated levels of metals, e.g., cadmium (Cd), within their cells. Selenium (Se) may increase the tolerance of plants to abiotic stress caused by the presence of heavy metal in the environment. Depending on its form (oxidation state, organic/inorganic), Se influences plant growth, secondary metabolite content, and biotic stress, as well as incorporates into shoots, providing economic and health benefits for consumers. So far, there are no data on the influence of organic Se(IV) on plants. Our study aimed to determine the effect of organic Se(IV) on the growth, active compound levels (anthranoids, polyphenols), and ultrastructure of St. John\'s wort without and under cadmium stress. The phytochemical analysis and microscopic examination was performed on shoots from different days of St. John\'s wort in vitro culture on a few variants of Murashige and Skoog medium with Cd (25 and 400 µM) and/or organic Se (IV). Exposure to Se(IV) did not affect hypericins but increased the polyphenol content in the shoots and the biomass. Se(IV) caused an increase in starch grain number in chloroplasts, whereas Cd exposure resulted in the degradation of the chloroplast structure, increased cell vacuolation, as well as swollen mitochondrial cristae. The addition of Se(IV) to these combinations reduced the degree of degradation and growth inhibition and a high content of Se(IV) in plants was observed. Se(IV) had no impact on Cd content at environmental Cd concentrations, but showed an effect at extremely high Cd concentrations. Thus, organic Se(IV) has a beneficial effect on St. John\'s wort growth, polyphenol content, and incorporation in shoots and prevents Cd toxicity. Media enriched with organic Se(IV) have both economic advantages and health benefits due to a higher plant growth rate and increased concentrations of polyphenols with strong antioxidant properties, relatively enriched with Se. However, organic Se(IV) should be used with caution in polluted areas. In perspective, speciation analysis and molecular study are crucial to understand the fate and effect of Se (IV) on plants.

The wound-healing effect of St. John\'s Wort (SJW) is mainly attributed to hyperforin (HP), but its low stability restricts its topical administration. This study investigates how \"free\" HP-rich SJW extract (incorporated into a bigel; B/SJW) and extract \"protected\" by nanostructured lipid carriers (also included in a biphasic semisolid; B/NLC-SJW) affect tissue regeneration in a rat skin excision wound model. Wound diameter, histological changes, and tissue gene expression levels of fibronectin (Fn), matrix metalloproteinase 8 (MMP8), and tumor necrosis factor-alpha (TNF-α) were employed to quantify the healing progress. A significant wound size reduction was achieved after applying both extract-containing semisolids, but after a 21-day application period, the smallest wound size was observed in the B/NLC-SJW-treated animals. However, the inflammatory response was affected more favorably by the bigel containing the \"free\" SJW extract, as evidenced by histological studies. Moreover, after the application of B/SJW, the expression of Fn, MMP8, and TNF-α was significantly higher than in the positive control. In conclusion, both bigel formulations exhibited beneficial effects on wound healing in rat skin, but B/SJW affected skin restoration processes in a comprehensive and more efficient way.

(1) Background: Laparoscopic staging is essential in gastric cancer (GC) to rule out peritoneal metastasis (PM). Hypericin, a plant-derived fluorescent compound, has been suggested to improve laparoscopic visualization of PM from GC. This prospective, single-arm, open-label clinical trial aimed to assess the feasibility and safety of oral hypericin administration as well as the suitability of fluorescence-guided laparoscopy (FGL) for improving the sensitivity and specificity of staging in GC patients (EudraCT-Number: 2015-005277-21; clinicaltrials.gov identifier: NCT-02840331). (2) Methods: GC patients received Laif® 900, an approved hypericin-containing phytopharmaceutical, once orally two to four hours before white light and ultraviolet light laparoscopy. The peritoneal cancer index was evaluated, biopsies taken and hypericin concentrations in serum and peritoneal tissue were determined by mass spectrometry. (3) Results: Between 2017 and 2021, out of 63 patients screened for eligibility, 50 patients were enrolled and treated per protocol. The study intervention was shown to be feasible and safe in all patients. Standard laparoscopy revealed suspicious lesions in 27 patients (54%), among whom 16 (59%) were diagnosed with PM. FGL identified suspicious areas in 25 patients (50%), among whom PM was confirmed in 13 cases (52%). Although hypericin concentrations in serum reached up to 5.64 ng/mL, no hypericin was detectable in peritoneal tissue biopsies. (4) Conclusions: FGL in patients with GC was shown to be feasible but futile in this study. Sufficient levels of hypericin should be ensured in target tissue prior to reassessing FGL with hypericin.

Hypericum perforatum (St. John\'s wort) has been described to be beneficial for the treatment of Alzheimer\'s disease (AD). Different extractions have demonstrated efficiency in mice and humans, esp. extracts with a low hypericin and hyperforin content to reduce side effects such as phototoxicity. In order to systematically elucidate the therapeutic effects of H. perforatum extracts with different polarities, APP-transgenic mice were treated with a total ethanol extract (TE), a polar extract obtained from TE, and an apolar supercritical CO2 (scCO2) extract. The scCO2 extract was formulated with silicon dioxide (SiO2) for better oral application. APP-transgenic mice were treated with several extracts (total, polar, apolar) at different concentrations. We established an early treatment paradigm from the age of 40 days until the age of 80 days, starting before the onset of cerebral β-amyloid (Aβ) deposition at 45 days of age. Their effects on intracerebral soluble and insoluble Aβ were analyzed using biochemical analyses. Our study confirms that the scCO2H. perforatum formulation shows better biological activity against Aβ-related pathological effects than the TE or polar extracts. Clinically, the treatment resulted in a dose-dependent improvement in food intake with augmentation of the body weight, and, biochemically, it resulted in a significant reduction in both soluble and insoluble Aβ (-27% and -25%, respectively). We therefore recommend apolar H. perforatum extracts for the early oral treatment of patients with mild cognitive impairment or early AD.

St. John\'s Wort preparations are used for the treatment of mild to moderate depression. They are usually well tolerated but can cause adverse reactions including liver toxicity in rare cases. To date, the mechanism(s) underlying the hepatotoxicity of St. John\'s Wort extracts are poorly investigated. We studied the hepatocellular toxicity of hypericin and hyperforin as the two main ingredients of St. John\'s Wort extracts in HepG2 and HepaRG cells and compared the effects to citalopram (a synthetic serotonin uptake inhibitor) with a special focus on mitochondrial toxicity and oxidative stress. In HepG2 cells, hypericin was membrane-toxic at 100 µM and depleted ATP at 20 µM. In HepaRG cells, ATP depletion started at 5 µM. In comparison, hyperforin and citalopram were not toxic up to 100 µM. In HepG2 cells, hypericin decreased maximal respiration starting at 2 µM and mitochondrial ATP formation starting at 10 µM but did not affect glycolytic ATP production. Hypericin inhibited the activity of complex I, II and IV of the electron transfer system and caused mitochondrial superoxide accumulation in cells. The protein expression of mitochondrial superoxide dismutase 2 (SOD2) and thioredoxin 2 (TRX2) and total and reduced glutathione decreased in cells exposed to hypericin. Finally, hypericin diminished the mitochondrial DNA copy number and caused cell necrosis but not apoptosis. In conclusion, hypericin, but not hyperforin or citalopram, is a mitochondrial toxicant at low micromolar concentrations. This mechanism may contribute to the hepatotoxicity occasionally observed in susceptible patients treated with St. John\'s Wort preparations.

The herb Hypericum perforatum, also referred to as St. John\'s wort, has drawn a lot of interest because of its potential therapeutic benefits in treating neurodegenerative illnesses. Due to the absence of effective therapies, illnesses like Alzheimer\'s and Parkinson\'s disease pose an increasing worldwide health concern. Because of its wide variety of phytochemicals, especially hyperforin, and hypericin, Hypericum perforatum is well known for its neuroprotective properties. These substances have proven to be able to affect different cellular processes linked to neurodegeneration. They can act as anti-inflammatory, antioxidant, and neurotransmitter system regulators, which may help halt neurodegenerative illnesses\' progression. The use of Hypericum perforatum extracts and its contents has shown encouraging results in research on animal models of neurodegenerative disorders. These advantages include higher nerve cell survival, lowered oxidative stress, and higher cognitive performance. Underscoring its versatile potential to combat neurodegeneration, Hypericum perforatum has neuroprotective mechanisms that modulate neuroinflammation and prevent apoptotic pathways. In conclusion, Hypericum perforatum shows tremendous promise as a potential treatment for neurological illnesses due to its wide variety of phytochemicals. To completely comprehend its specific mechanisms of action and turn these discoveries into efficient clinical therapies, additional research is needed. Investigating Hypericum perforatum\'s function in neurodegenerative disorders may present new opportunities for the advancement of ground-breaking therapeutic strategies.

This study aimed to determine the secondary metabolite profiles and antibacterial activity of H. perforatum L extracts against Gram-positive clinical isolates. The plant materials (Sample A and Sample B) were macerated with n-hexane, ethyl acetate and methanol (MeOH). The antibacterial activitiy of plant extracts and routinely used antibiotics were tested against Gram-positive bacteria. The secondary metabolite profiles of Sample A were determined by LC-Q-TOF-MS. The MIC values for n-hexane and ethyl acetate extracts of Sample A were lower than the susceptibility breakpoints of most broad-spectrum antibiotics (e.g. vancomycin, teicoplanin and linezolid) in a certain proportion of Gram-positive bacteria. The n-hexane extract of Sample A showed good antibacterial activity with MICs lower than the susceptibility breakpoint of teicoplanin in 58% of coagulase-negative staphylococci. The n-hexane and ethyl acetate extracts of Sample A had rich phloroglucinol constituents. The n-hexane and ethyl acetate extracts of Sample A could be alternative antibacterial agents against Gram-positive bacteria.

Hypericum perforatum (St. John\'s Wort) is a medicinal plant from the Hypericaceae family. Here, we sequenced the whole chloroplast genome of H. perforatum and compared the genome variation among five Hypericum species to discover dynamic changes and elucidate the mechanisms that lead to genome rearrangements in the Hypericum chloroplast genomes. The H. perforatum chloroplast genome is 139,725 bp, exhibiting a circular quadripartite structure with two copies of inverted repeats (IRs) separating a large single-copy region and a small single-copy region. The H. perforatum chloroplast genome encodes 106 unique genes, including 73 protein-coding genes, 29 tRNAs, and 4 rRNAs. Hypericum chloroplast genomes exhibit genome rearrangement and significant variations among species. The genome size variation among the five Hypericum species was remarkably associated with the expansion or contraction of IR regions and gene losses. Three genes-trnK-UUU, infA, and rps16-were lost, and three genes-rps7, rpl23, and rpl32-were pseudogenized in Hypericum. All the Hypericum chloroplast genomes lost the two introns in clpP, the intron in rps12, and the second intron in ycf3. Hypericum chloroplast genomes contain many long repeat sequences, suggesting a role in facilitating rearrangements. Most genes, according to molecular evolution assessments, are under purifying selection.

BACKGROUND: Hypericum species are widely acknowledged for their biological attributes, with notable attention being paid to Hypericum perforatum, commonly known as St. John\'s wort (SJW) within the Hypericum section of the Hypericaceae family. This species is among the most thoroughly investigated herbal medicines, particularly in terms of its application in the management of mild to moderate depression. SJW is used to treat depression, menopausal symptoms, attention-deficit hyperactivity disorder (ADHD), somatic symptom disorder, obsessive-compulsive disorder, and skin conditions, such as wounds and muscle pain. However, the usefulness and effectiveness of SJW for male sexual and reproductive health (SRH) are not well known.
OBJECTIVE: To assess the current evidence in the literature on the effect of SJW on male SRH.
METHODS: This narrative review followed a predetermined protocol and used MEDLINE and PubMed to identify articles published in English on the effects of SJW on male SRH. The search used various keywords, such as \"Hypericum Perforatum\", \"St. John\'s Wort\", and terms related to sexual and reproductive health issues. Articles published between the inception of the database and August 2023 were included.
RESULTS: We identified 12 articles published from 1999 to 2019, the majority of which were experimental and conducted on animals. These studies demonstrate variability in terms of design, sample size, type of SJW extract used, the dosage administered, and duration of treatment. Studies have indicated potential sexual dysfunction (SD) due to SJW, which includes reduced libido, delayed ejaculation, delayed orgasm, and erectile dysfunction. Additionally, reproductive toxicity has been suggested, as evidenced by spermicidal effects through the inhibition of sperm motility, abnormal spermatozoa, chromosomal aberrations, and DNA denaturation. Furthermore, some studies have reported potential adverse events during maternal exposure, inhibition of fertilization, and disruption of reproductive parameters.
CONCLUSIONS: Our review suggests that the safety and efficacy of SJW in the treatment of human SRH remain unclear. Further comprehensive, well-designed studies with larger samples, longer exposure periods, and specific dosages are needed to clarify SJW\'s effects of SJW. Therefore, consultation with healthcare professionals before using herbal remedies or supplements is crucial.

Consumption of St. John\'s wort plant is high worldwide due to its various medicinal properties. However, herbal products containing St. John\'s wort may be contaminated with toxic metals. This is often related to contamination of both water and the atmosphere, lack of proper cultivation methods, and inadequate plant storage conditions, as well as a lack of stricter sanitary supervision. A safety assessment of copper (Cu), lead (Pb), cadmium (Cd) and arsenic (As) content in 23 products containing St. John\'s wort (pharmaceutical herbal products, food supplements and traditional herbal remedies) sold in the metropolitan area of Mexico City was conducted. The analysis of metals was determined using a graphite-furnace atomic absorption spectrometer. All herbal products were contaminated with Cu, Pb, Cd and As. The pharmaceutical herbal items showed less contamination by metals. The daily human intake (DHI) values for Pb exceeded the permissible limits in the group of traditional herbal remedies. The DHI calculation for As exceeded the permitted intake values for all items in the group of traditional herbal remedies, five food supplements and one pharmaceutical herbal product. The hazard indicator calculation of the non-carcinogenic cumulative risk values for traditional herbal remedies was greater than 1, suggesting a risk to human health.