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Background: Depression is a complex mental disease whose incidence increases every year; 300 million people worldwide currently suffer from it. Women are more likely to suffer from depression, twice the rate as men. It is one of the few illnesses that can lead to suicide, which makes it very dangerous – currently, 700,000 people die from suicide and it is the 4th most common cause of death in people aged 15-29. The treatment strategies for depression is a big challenge for physicians, pharmacists, scientists and classic remedies cause many side effects. Therefore, natural phytotherapy with herbs can prove to be a good solution. Phytotherapy is a popular treatment method used for centuries in Chinese medicine or Ayurveda. Materials and methods: The study conducted a comprehensive database search PubMed, ClinicalKey and MedNar covered the years 2015 - 2024 to provide the most up-to-date data. 13 randomized controlled trials and 1 meta – analysis were included in the systematic review. Results: Many plants show anti-inflammatory, antioxidant and cognitive enhancing effects, which are particularly important in depression. In the treatment of depression, plants such as Crocus sativus L. stigma , Lavandula angustifolia, Hypericum perforatum L. and Curcuma longa L. have proven to be effective. They show good effectiveness in human studies and alleviate the symptoms of depression. Herbal products can support classical pharmacotherapy, but this requires further research. Non-commercial clinical trials in the future should provide answers to research questions: at what stage of treatment of patients with MDD will the use of phytochemicals be most appropriate in terms of therapy efficacy and safety for the patient. Conclusions: Crocus sativus L. stigma , Lavandula angustifolia, Hypericum perforatum L. and Curcuma longa L. in modern medicine can help improve the well-being of patients with depression. The use of herbs as an intervention was associated with a decrease in the concentration of proinflammatory cytokines and an overall improvement in the mood of patients. Further research should be undertaken into combining both therapies in order to improve patients' quality of life and reduce treatment costs. [ABSTRACT FROM AUTHOR]

Background: The recurring actions and intrusive thoughts that characterise obsessive–compulsive disorder (OCD), a long-term mental illness, are known as compulsions. The cornerstones of conventional treatment are psychological counselling and prescribed medication; nonetheless, interest in complementary therapies has grown. This review looks at how well Ashwagandha, curcumin, milk thistle, valerian root, and St. John's wort may help with OCD symptoms. Methods: To assess these herbal supplements' potential for therapeutic benefit, case reports and clinical trials were examined. Results: Curcumin, which contains anti-inflammatory and neuroprotective properties, has shown promise in reducing the severity of OCD symptoms. Traditionally used to treat depression, St. John's wort has shown some potential in lowering anxiety and compulsive behaviour. The herb milk thistle, which is mainly used for liver protection, did not affect OCD symptoms. Anxiolytic valerian root barely offered relief from symptoms associated with anxiety; it has only little effect on obsessions and compulsions. The adaptive Ashwagandha has demonstrated a great deal of promise in lowering stress and enhancing general well-being, which may help with symptom alleviation. Although the initial results are favourable, larger scale randomised controlled trials are necessary to validate reliability and efficacy. Conclusion: This study illustrates how herbal supplements may be used in addition to conventional medications as adjunctive treatments for OCD. [ABSTRACT FROM AUTHOR]

Chronic stress is a key factor in the development of depression. It leads to hyperactivation of the hypothalamic–pituitary–adrenal (HPA) axis, which in turn increases the formation of glucocorticoids (GCs). Chronically elevated GC levels disrupt neuroplasticity and affect brain lipid metabolism, which may, ultimately, contribute to the development of depression. This study aimed to investigate the effects of the antidepressants St. John's Wort extract and escitalopram on lipid metabolism in vivo. Therefore, repeated corticosterone injections were used to induce depression-like behavior in rats. Male Sprague–Dawley rats were stressed with corticosterone injections (40 mg/kg, s.c.) over 22 consecutive days and were concomitantly treated with varying doses of the St. John's wort extract Ze 117 (30, 90 or 180 mg/kg, p.o.) or escitalopram (10 mg/kg, p.o.) and behavioral changes were evaluated using a modified forced swim test. The results indicate that repeated corticosterone injections significantly decreased the latency to first immobility. Furthermore, co-treatment of corticosterone with Ze 117 increased latency to first immobility significantly compared to rats treated with corticosterone alone. To further investigate the biochemical effects of corticosterone-induced stress, as well as the possible counter-regulation by antidepressants, the lipidomes of the plasma and hippocampus samples were analyzed by shotgun mass spectrometry. Corticosterone-induced stress significantly altered key lipid metabolites in the plasma but not in the hippocampal samples. In the hippocampus, however, specific glycerophospholipids such as lysophosphatidylethanolamines (LPEs) increased with escitalopram treatment and with Ze 117, both showing significant correlations with behavioral parameters. In summary, our study shows significant behavioral- and lipidome-altering processes with Ze 117 and escitalopram in rat plasma and hippocampal samples, thereby providing new targets and biomarker ideas for clinical diagnosis and antidepressant intervention. [ABSTRACT FROM AUTHOR]

Approximately one-third of Americans use healthcare approaches including herbs and botanicals, such as St. John's wort (SJW), to improve overall well-being, gain control over their health, and manage the adverse reactions of conventional therapies. This article examines the use of SJW in cancer care, discussing its pharmacokinetics, toxicity, and potential interactions with cancer treatments while emphasizing the importance of patient education and collaboration between oncology nurses and pharmacists to ensure safe and effective care. [ABSTRACT FROM AUTHOR]

Abstract Background Obstructive sleep apnea (OSA) is one of the foremost potential severe disorders, with frequent episodes of complete or partial obstructions of the upper airway during sleep. Therefore, several attempts to find an effective pharmacotherapy by repurposing several drugs such as serotonin reuptake inhibitors (SRIs) and norepinephrine and dopamine reuptake inhibitors (NDRIs) were recently considered as alternative therapeutic strategy. So, in this review, we will present non-conventional pharmacological approaches for managing OSA via either repurposing selected natural products or traditional medicine. Evidence acquisition Scientific databases and literature reviewed in the last twenty years were screened using different keywords related to OSA; exclusion criteria were applied based on the accessibility and the ability of the sources to follow evidence-based approaches. The eligible resources were classified into two main categories: clinical-based studies and preclinical studies. The findings of these studies were analyzed and discussed in light of current evidence derived from recent studies. Findings Several natural components and traditional formulas were found to regulate several molecular targets involved in OSA pathogenesis, supported by several in-vitro and in-vivo studies. Also, natural products subjected to clinical trials give promising results. Still, there are some limitations, such as involving a small number of patients depending on subjective yet acceptable scores rather than objective scores, a lack of positive control groups, or a small number of patients. Conclusion Therapeutic protocols should consider non-conventional polypharmacological strategies targeting all OSA aspects. Hence, there is an opportunity to reposition some well-defined natural products, such as cinnamic acid derivatives, isoflavones, and lignans, as several evidences from in-vitro, in-vivo, and clinical trials support their potential efficacy in the management of OSA.

St. John's wort (Hypericum perforatum L.) is a medicinal and aromatic plant of rapidly increasing importance. The cultural production of this species, which is of economic importance due to its medicinal properties, is limited. One of the main ways to increase production is to develop cultivars. Thus, the homogeneous raw material required for a standard product will be provided. This study aimed to determine the characteristics of natural populations to obtain productive cultivars with high hypericin and hyperforin that can meet market demands. In addition to yield and quality values, other characteristic features of the plant such as flower diameter, petal length and petal width, which directly affect productivity, were revealed in the study. The study was conducted under field conditions for two years with three replications. Fresh flower weight among the populations varied between 30.15 and 240.28 g/plant, while the hypericin ratio varied between 51.32 and 105.31 (mg/100 g). The study determined a wide variation among the populations, and the populations with superior characteristics were included in the breeding program. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is one of the foremost potential severe disorders, with frequent episodes of complete or partial obstructions of the upper airway during sleep. Therefore, several attempts to find an effective pharmacotherapy by repurposing several drugs such as serotonin reuptake inhibitors (SRIs) and norepinephrine and dopamine reuptake inhibitors (NDRIs) were recently considered as alternative therapeutic strategy. So, in this review, we will present non-conventional pharmacological approaches for managing OSA via either repurposing selected natural products or traditional medicine. Evidence acquisition: Scientific databases and literature reviewed in the last twenty years were screened using different keywords related to OSA; exclusion criteria were applied based on the accessibility and the ability of the sources to follow evidence-based approaches. The eligible resources were classified into two main categories: clinical-based studies and preclinical studies. The findings of these studies were analyzed and discussed in light of current evidence derived from recent studies. Findings: Several natural components and traditional formulas were found to regulate several molecular targets involved in OSA pathogenesis, supported by several in-vitro and in-vivo studies. Also, natural products subjected to clinical trials give promising results. Still, there are some limitations, such as involving a small number of patients depending on subjective yet acceptable scores rather than objective scores, a lack of positive control groups, or a small number of patients. Conclusion: Therapeutic protocols should consider non-conventional polypharmacological strategies targeting all OSA aspects. Hence, there is an opportunity to reposition some well-defined natural products, such as cinnamic acid derivatives, isoflavones, and lignans, as several evidences from in-vitro, in-vivo, and clinical trials support their potential efficacy in the management of OSA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BackgroundDepression is a complex mental disease whose incidence increases every year; 300 million people worldwide currently suffer from it. Women are more likely to suffer from depression, twice the rate as men. It is one of the few illnesses that can lead to suicide, which makes it very dangerous – currently, 700,000 people die from suicide and it is the 4th most common cause of death in people aged 15-29. The treatment strategies for depression is a big challenge for physicians, pharmacists, scientists and classic remedies cause many side effects. Therefore, natural phytotherapy with herbs can prove to be a good solution. Phytotherapy is a popular treatment method used for centuries in Chinese medicine or Ayurveda.Materials and methodsThe study conducted a comprehensive database search PubMed, ClinicalKey and MedNar covered the years 2015 - 2024 to provide the most up-to-date data. 13 randomized controlled trials and 1 meta – analysis were included in the systematic review.ResultsMany plants show anti-inflammatory, antioxidant and cognitive enhancing effects, which are particularly important in depression. In the treatment of depression, plants such as Crocus sativus L. stigma, Lavandula angustifolia, Hypericum perforatum L. and Curcuma longa L. have proven to be effective. They show good effectiveness in human studies and alleviate the symptoms of depression. Herbal products can support classical pharmacotherapy, but this requires further research. Non-commercial clinical trials in the future should provide answers to research questions: at what stage of treatment of patients with MDD will the use of phytochemicals be most appropriate in terms of therapy efficacy and safety for the patient.ConclusionsCrocus sativus L. stigma, Lavandula angustifolia, Hypericum perforatum L. and Curcuma longa L. in modern medicine can help improve the well-being of patients with depression. The use of herbs as an intervention was associated with a decrease in the concentration of proinflammatory cytokines and an overall improvement in the mood of patients. Further research should be undertaken into combining both therapies in order to improve patients’ quality of life and reduce treatment costs.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Depression is a prevalent mental illness. In addition to being a substantial contribution to the overall global disease burden, depression is one of the main causes of disability worldwide. Complementary therapies are necessary because of the drawbacks of standard antidepressant therapy, including side effects, even though the former can help reduce depression symptoms and avoid relapse of the illness. Because they have fewer side effects and are less expensive than other therapies for depression, herbal medications have drawn a lot of interest recently. Compared to synthetic medications, herbal plants have fewer adverse effects and exhibit antidepressant properties. As such, they may be able to help people who are depressed. Because herbs have fewer adverse effects than conventional drugs, many people prefer them for symptom treatment. If traditional medications aren't working for you because of side effects, poor efficacy, or accessibility issues, using phytomedicine can be a good alternative. This review will concentrate on herbs that are used to cure depression. [ABSTRACT FROM AUTHOR]

St. John’s wort (Hypericum perforatum L.) is a medicinal and aromatic plant of rapidly increasing importance. The cultural production of this species, which is of economic importance due to its medicinal properties, is limited. One of the main ways to increase production is to develop cultivars. Thus, the homogeneous raw material required for a standard product will be provided. This study aimed to determine the characteristics of natural populations to obtain productive cultivars with high hypericin and hyperforin that can meet market demands. In addition to yield and quality values, other characteristic features of the plant such as flower diameter, petal length and petal width, which directly affect productivity, were revealed in the study. The study was conducted under field conditions for two years with three replications. Fresh flower weight among the populations varied between 30.15 and 240.28 g/plant, while the hypericin ratio varied between 51.32 and 105.31 (mg/100 g). The study determined a wide variation among the populations, and the populations with superior characteristics were included in the breeding program.

Considering it contains a variety of physiologically active compounds, including flavonoids, common phenols, and essential oils (EOs), St. John’s wort (Hypericum perforatum L.) is a common plant in Bulgaria that is predominantly used in folk medicine to cure various disorders. Determining the chemical makeup of St. John’s wort inflorescences that were gathered from northern Bulgaria was the purpose of this investigation. The antioxidant activity of H. perforatum L. extracts was assessed using 1,1-diphenyl-2-picrilhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and Trolox equivalent antioxidant capacity (TEAC) tests on methanol extract. The amount of EO obtained by water distillation was 0.08%, with its main components (over 3%) being n-nonane (27.46%), β-sesquiphellandrene (11.17%), heptanal dimethyl acetal (5.94%), ethyl hexyl ketone (5.93%), undecane (3.75%), sabinene (3.3%), and tridecyl alcohol (3.1%). Methanol extracts were obtained from the inflorescences, with the total flavonoid content determined as 8.66 mg quercetin equivalents (QE)/mg and total phenolic content as 271.33 mg Gallic acid equivalent/g. The FRAP assay yielded 493.07 µmol/L of antioxidant activity, while the TEAC assay yielded 106.39 µmol/L, respectively. Our findings enable a comprehensive characterization of H. perforatum from Bulgaria and an assessment of its oil suitability for potential industrial applications. Additionally, the results could guide the selection of specimens for future targeted breeding efforts.

(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. [ABSTRACT FROM AUTHOR]

Hypericum haplophylloides Halácsy & Bald is an endemic St. John's wort of Albania described by Halácsy in 1892, with locus classicus in Llogara, Vlora district. According to Meyer, the distribution of this species is wider in Albania, and it's represented by two subspecies: H. haplophylloides subps. haplophylloides and H. haplophylloides subsp. devollense, which are phyto-geographically divided and grow in different substrate types. Described almost a century later, there are still a lot of scientific discussions about accepting of these subspecies as new taxa, considering them as ecotypes or just high phenotypic plasticity of the species. In this study we aim to notice if there is any significant statistical difference between them based on some parametric measurements of leaves, sepals, and fruits; features that make the differences according to F.K. Meyer. The results indicated that: there is no significant difference between the two subspecies related to length of leaves, but the leaves width of subsp. devollense is significantly bigger. There is a significant difference between subspecies concerning the fruit's size. They are larger to subsp. haplophylloides, but significant differences of fruit's size exist even between different populations of the same subspecies. Subsp. haplophylloides results to have lengthier sepals than subsp. devollense, but the sepals are wider to subsp. devollense. These wide variations which are not considered by Meyer, probably reflection of different ecological conditions of habitats where H. haplophylloides grows, supporting the presence of different ecotypes and/or high phenotypic plasticity. Genetics studies are highly recommended. [ABSTRACT FROM AUTHOR]

Tacrolimus is metabolized by cytochrome P450 3A (CYP3A) and is susceptible to interactions with the CYP3A and P‐glycoprotein inducer St. John's Wort (SJW). CYP3A isozymes are predominantly expressed in the small intestine and liver. Prolonged‐release tacrolimus (PR‐Tac) is largely absorbed in distal intestinal segments and is less susceptible to CYP3A inhibition. The effect of induction by SJW is unknown. In this randomized, crossover trial, 18 healthy volunteers received single oral tacrolimus doses (immediate‐release [IR]‐Tac or PR‐Tac, 5 mg each) alone and during induction by SJW. Concentrations were quantified using ultra‐high performance liquid chromatography coupled with tandem mass spectrometry and non‐compartmental pharmacokinetics were evaluated. SJW decreased IR‐Tac exposure (area under the concentration‐time curve) to 73% (95% confidence interval 60%‐88%) and maximum concentration (Cmax) to 61% (52%‐73%), and PR‐Tac exposure to 67% (55%‐81%) and Cmax to 69% (58%‐82%), with no statistical difference between the 2 formulations. The extent of interaction appeared to be less pronounced in volunteers with higher baseline CYP3A4 activity and in CYP3A5 expressors. In contrast to CYP3A inhibition, CYP3A induction by SJW showed a similar extent of interaction with both tacrolimus formulations. A higher metabolic baseline capacity appeared to attenuate the extent of induction by SJW. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Exposure to hypericin induces cytotoxicity in hepatic HepG2 and HepaRG cells. • Hypericin decreases mitochondrial ATP production in HepG2 cells. • Hypericin inhibited the activity of complex I, II and IV of the ETS in HepG2 cells. • Hypericin induces mitochondrial oxidative stress in HepG2 cells. • Hypericin diminishes the mitochondrial DNA copy number and causes cell necrosis. [ABSTRACT FROM AUTHOR]

Hypericum perforatum L. hairy root clones cultured under dark (HR1) and photoperiod (HR2) conditions were comparatively assessed for the contents of phenolic compounds and their inhibitory potential against enzymes related to depression, neurodegeneration, diabetes and hyperlipidemia. In silico docking methods were performed to examine the molecular interactions between the preeminent phenolics in HR samples and target enzymes (monoamine oxidase-A, acetylcholinesterase, butyrylcholinesterase, tyrosinase, α-amylase, α-glucosidase, lipase and cholesterol esterase). Phytochemical analyses showed that HR1 exhibited a better ability for producing vanillic acid, syringic acid, flavan-3-ol derivatives and flavonol glucosides, whereas HR2 were distinguished by their elevated biosynthesis of naphthodianthrones (pseudohypericin and protopseudohypericin) and xanthones. Importantly, photoperiod exposure significantly increased the accumulation of compounds with acetylcholinesterase, α-glucosidase, lipase, and cholesterol esterase inhibitory activity. In contrast, HR1 cultures had comparable or even higher monoamine oxidase-A, butyrylcholinesterase, tyrosinase, and α-amylase inhibition in comparison to HR2 cultures. When docking data were analysed, procyanidin B2, paxanthone, and garcinone B demonstrated the lowest binding energies towards tested enzymes denoting their contribution to the bioactivities of HR cultures. Outgoing data pointed out that H. perforatum HR cultured under darkness and photoperiod could be considered as a rich source of phenolics with a wide array of biological properties.Key message: Exposure of Hypericum perforatum L. hairy root cultures to photoperiod conditions enhances the production of naphthodianthrones and xanthones with acetylcholinesterase, α-glucosidase, lipase, and cholesterol esterase inhibitory activities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this study, the effect of ultrasound pretreatment (at 40 kW power, for 20 min) with single partial solvent including water and ethanol and two partial solvents containing water/ethanol in the form of 30% (water): 70% (ethanol) and 60% (water): 40% (ethanol), were considered on the extraction efficiency, total phenolic and flavonoid compounds, as well as the free radical inhibition rate of the St. John’s wort (Hypericum perforatum L.) extract. In order to analyze the data, a completely randomized design was used in three replications, and the comparison of means was done by Duncan's multi-range test, at the probability level of α=1%, and using SPSS 14. Based on the results, the highest amount of extraction efficiency (18.3 %), total phenolic (0.295 mg GAE/g dw) and flavonoid (0.105 mg QE/g dw) compounds and the inhibition rate of free radicals (84.21 %) was measured in the samples pre-treated with ultrasound along with two partial solvents [30% (water): 70% (ethanol)] and the lowest amount of extraction efficiency (4.21%), total phenolic (0.051mg GAE/g dw) and flavonoid (0.0115 mg QE/g dw) compounds as well as free radical inhibition rate (47.53 %) was specified in water (100 %) solvent. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Literature reports randomized trials have examined herbal drugs and other smoking cessation therapies such as aromatherapy acupuncture but no comprehensive overview of the overall results has been provided. The present systematic review and meta-analysis aimed to describe the overall effectiveness and safety of herbal medicines. Methods: This study was conducted from December 2020 to April 2021 by searching seven databases. Herbal drugs have been shown to help people quit smoking in randomized controlled studies. Two teams of researchers independently extracted the data. Findings: A total of 12 trials with 762 smokers were included in this study. The heterogeneity I2 was 43.6% with P=0.03 (Cochrane Q test) and χ2=15.77. The overall odds ratio (OR) at 95% confidence interval (CI) was 0.91 (0.68- 1.20) which shows a protective factor of herbal preparations and very low heterogeneity. The herbal treatments such as Vernonia cinerea, St. John’s Wort, and lavender essential oil were significantly related to a higher continuous abstinence rate (CAR) compared to the controls with risk ratio (RR): 2.13 (0.57-4.61) at week 8; RR: 2.72 (0.77-5.3) at week 12; and RR: 2.77 (0.37-1.13) at week 24. A 7-day point abstinence rate (PAR) at week 8 was RR: 1.24 (0.81-6.34) with 95% CI; RR: 2.09 (0.93-8.29) at week 12, and RR: 2.11 (0.3-3.08) at week 24.Black pepper and lime were better in craving reduction than the placebo group. This study found no significant difference between the treatment and control groups in adverse effects, despite some minor side effects with herbal drugs. Conclusion: The results of this study showed herbal treatments have the potential to help smokers quit the habit. Further well designed trials comparing standardized herbal medicines with conventional therapy and placebo are recommended to reinforce this data.

There has been a steady increase in people with symptoms of depression over the past several years (since 2011). The further increase in stress and depression in the early part of the COVID‐19 pandemic was accompanied by an increase in unmet mental health needs. Many have turned to complementary and alternative medicine (CAM) therapies such as bright‐light therapy, yoga, meditation, and dietary supplements like St. John's wort or folic acid. The reliability of evidence for use of CAM therapies for depression has remained low. There are few randomized controlled trials (RCTs) in the current literature and poor methodology in many of the trials that are available. This state of the science review examines current published guidelines, meta‐analyses, systematic reviews, and RCTs regarding use of CAM therapies in the management of depression. [ABSTRACT FROM AUTHOR]

Commonly used to treat mood disorders, St. John's Wort (Hypericum perforatum) is a popular herb in the natural health products industry. The potency of its active ingredients can be determined using a number of different analytical methods, but it is more widely determined using high performance liquid chromatography (HPLC). While monographs in the United States Pharmacopeia (USP) can often be relied upon for suitable analytical methods, the method proposed for determining hypericin content in St. John's Wort products is inefficient in carrying out this purpose. This paper presents a modified new HPLC method for determining the hypericin content that can also be used for St. John's Worts capsules and tablets by making use of purified hypericin as a chemical standard instead of oxybenzone, applying a wavelength of 588 nm during analysis and utilizing a binary instead of ternary mobile phase gradient. The resulting method and sample chromatograms provide better resolved, more easily identifiable peaks, shorter run time, and increased sustainability compared to the original USP method. This proposed method was developed using the more refined ultra-high performance liquid chromatography (UHPLC) and serves as a more accurate and reliable method for determining hypericin content in St. John's Wort. [ABSTRACT FROM AUTHOR]

Hypericum perforatum (Hypericaceae), known as Saint John’s wort (SJW), has been used in different systems of traditional medicine such as Chinese traditional medicine, Greek traditional medicine, and Islamic traditional medicine. The plant and its active constituents such as hyperforin and hypericin have a wide range of medicinal uses, particularly as anti-depressant, wound-healing, and antibacterial agents. In recent decades, many clinical trials have been performed to investigate the safety and efficacy of this medicinal plant. However, to the best on our knowledge, there is no comprehensive review article in this regard. In the current study, we aim to have a comprehensive review of the clinical trials of SJW to evaluate its efficacy and safety as well as its application in traditional medicine. Clinical studies investigating the safety, interactions, and efficacy of SJW were identified and summarized, including contributions from 2000 until December 2021. According to the results, these clinical studies were divided into three main categories based on the type of disease: psychiatric, endocrine, and skin problems. Important details of the studies, including the type and duration of the study, the type and percentage of the effective compounds or the extract used, the number of patients, and the obtained results were also discussed. In addition, co-administration and drug interaction of SJW with other drugs were summarized. SJW is a valuable medicinal plant, especially for psychiatric disorders. However, precautions should be taken while administrating the plant.

Microshoot agitated and bioreactor cultures (PlantForm bioreactors) of three Hypericum perforatum cultivars (Elixir, Helos, Topas) were maintained in four variants of Murashige and Skoog medium (MS) supplemented with 6-benzylaminopurine (BAP) and 1-naphthaleneacetic acid (NAA) (in the range of 0.1–3.0 mg/L). In both types of in vitro cultures, the accumulation dynamics of phenolic acids, flavonoids, and catechins were investigated during 5- and 4-week growth cycles, respectively. The contents of metabolites in methanolic extracts from biomasses collected in 1-week intervals were estimated by HPLC. The highest total contents of phenolic acids, flavonoids, and catechins were 505, 2386, and 712 mg/100 g DW, respectively (agitated cultures of cv. Helos). The extracts from biomass grown under the best in vitro culture conditions were examined for antioxidant and antimicrobial activities. The extracts showed high or moderate antioxidant activity (DPPH, reducing power, and chelating activity assays), high activity against Gram-positive bacteria, and strong antifungal activity. Additionally, experiments with phenylalanine feeding (1 g/L) in agitated cultures were performed reaching the highest enhancement of the total contents of flavonoids, phenolic acids, and catechins on day 7 after the addition of the biogenetic precursor (2.33-, 1.73- and 1.33-fold, respectively). After feeding, the highest accumulation of polyphenols was detected in the agitated culture of cv. Elixir (4.48 g/100 g DW). The high contents of metabolites and the promising biological properties of the biomass extracts are interesting from a practical point of view. [ABSTRACT FROM AUTHOR]

St. John's wort (Hypericum perforatum) has been used in traditional medicine for centuries for different conditions, including kidney and lung ailments, insomnia, depression, and to aid wound healing. The objective of the present bibliometric analysis is to capture the characteristics of research publications on the topic of St. John's wort. Searches were run on April 09, 2021, and results were exported on the same day to prevent discrepancies between daily database updates. Trends associated with this subset of publications were identified and presented. Bibliometric networks were constructed and visualized using the software tool VOSviewer. A total of 1,970 publications were published by 5,849 authors across 961 journals from 1859 to 2021. Beginning in the late 1990s, a steep increase was found in the volume of publication on this topic. The journal that published the largest number of publications was Phytotherapy Research. The most productive countries included Germany and the United States. The present study provides the characteristics of the St. John's wort literature that allows understanding of the past, present, and future of research in this area. It is a useful evidence-based framework on which to base future research actions and academic directions. [ABSTRACT FROM AUTHOR]

Hypericum perforatum L., is a sprawling, leafy herb that grows in open, disturbed areas, known as St. John's wort, has a variety of secondary metabolites that can be used for medicinal and therapeutic purposes. Heavy metals have become the most dangerous pollutants in the environment. The effect of cadmium chloride, lead nitrate, silver nitrate, methyl jasmonate, and salicylic acid was studied on several morphometric and biochemical features of St. John's wort simultaneously using the Taguchi statistical method. The results showed cadmium chloride and lead nitrate reduced the morphometric and biochemical properties of St. John's wort while salicylic acid compensated for the adverse effects of heavy metals. Simultaneously, use of salicylic acid and silver nitrate with cadmium chloride and lead nitrate reduced the toxic effects of these metals on morphometric properties. Methyl jasmonate improved growth characteristics at low levels and inhibited at higher levels. Also, according to the results, salicylic acid could reduce the effects of heavy metals on the biochemical properties, while silver nitrate acts like heavy metals, especially at higher levels. Salicylic acid reduced the harmful effects of these heavy metals and at all levels was able to create a better induction effect on St. John's wort. These elicitors mainly changed the adverse effects of heavy metals by strengthening the pathways of the antioxidant system in St. John's wort. The research assumptions were validated, which suggests that the Taguchi method could be considered in an optimum culture of medicinal plants under different treatments such as heavy metals and elicitors. [ABSTRACT FROM AUTHOR]

Background. Depression is the most common mental disorder, affecting about 3.8% of the population worldwide. Clinical symptoms of depression include sadness, anxiety and frequent mood swings, among others. Selective serotonin reuptake inhibitors (SSRIs), psychotherapy and behavioral therapy are commonly used for the treatment of this condition. Since SSRIs are associated with various side effects, extract of St. John's wort (SJW) has been suggested as an effective alternative. However, there are conflicting studies regarding its efficacy. Many studies have reported positive outcomes with low adverse effects, while others did not find it to be a suitable alternative. Objectives. To analyze the available studies using SJW for depression therapy and to thoroughly evaluate its effectiveness compared to SSRIs and placebo. Materials and methods. Relevant articles for our meta-analysis were found using Medline (via PubMed), Cinahl (via EBSCO), Scopus, and Web of Sciences databases. Studies were included as per the predefined Population, Intervention, Comparison, Outcomes and Study (PICOS) criteria. A demographic summary of the patients treated with either SJW, placebo or SSRIs was collected and Hamilton Depression Rating Scale (HAMD) scores were extracted. Risks of bias analysis, diagnostic odds ratio (OR), risk ratio (RR), and sensitivity calculation were evaluated using Revman software, and the publication bias was assessed using MedCalc software. Results. Fourteen clinical trials with a total of 2270 depression patients were included in accordance with the inclusion criteria. All analyzed papers were published between 2000 and 2022. For patients treated with either SSRIs or SJW, a pooled OR of 2.44 with a 95% confidence interval (95% CI) of 1.33-4.45 was obtained. The data were heterogeneous, with a tau2 value of 0.54, χ2 value of 31.05, degrees of freedom (df) value of 7, I2 value of 77%, and an overall Z-value of 2.90 with p = 0.004. Conclusions. Our research supports the use of SJW as it reduced the number of depressive patients and their HAMD scores while having fewer risks and side effects than conventional medications. [ABSTRACT FROM AUTHOR]

Plants plastically alter their metabolism in response to environmental stimuli, which induces changes in the accumulation of specialized metabolites. This ability can be utilized to manipulate plant phytochemistry in a desired direction. However, the abundance of secondary metabolites in the different plant species, especially medicinal, is enormous; therefore, it is difficult to establish a clear direction for the effects of metabolic modulators on phytochemical composition, especially given the possibility of using different types thereof. In order to gain insight into these changes, we investigated the effects of foliar-applied chitosan (ChL, 100 mg/L), selenium (Se, 10 mg/L), salicylic acid (SA, 150 mg/L), or an equal volume mixture thereof on Hypericum perforatum L. metabolism. Selenium and SA proved to be the more effective than ChL in enhancing the accumulation of phenolic compounds. The greatest increase was found in the concentration of neochlorogenic acid after Se-spraying. The treatment with the elicitors generally increased the concentration of identified flavonoids, but not the level of naphthodianthrone or phloroglucinol metabolites. The most pronounced response was observed on day 10 following the application of the compounds, and is likely the consequence of elevated levels of O 2 −˙, free proline, and modulated activity of enzymatic antioxidants. [Display omitted] • The metabolic modulators increased the levels of identified flavonoids. • The highest accumulation of specialized metabolites was found on the 10th day of elicitation. • Se and SA were indicated as the most effective metabolic modulators. • Se caused the greatest increase in neochlorogenic acid concentration. • Elicitor treatments increased the levels of ROS, especially O 2 −˙, and free proline. [ABSTRACT FROM AUTHOR]

The usage potential of chemical and green synthesized cobalt (Co) and nickel (Ni) nanoalloys (CoNiNAs) as mortar additives at different ratios was evaluated. The CoCl _2 and NiCl _2 metallic salt solutions were mixed in volume ratios of 1-1, 1-2, and 2-1 and reduced with NaBH _4 and St. John's Wort aqueous extract, respectively. The obtained Co-Ni based complex nanoalloys were analyzed by Ultraviolet-Visible Spectroscopy (UV-Vis), X-Ray Diffraction Analysis (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), Fourier Transform Infrared Spectroscopy (FT-IR), and Dynamic Light Scattering Particle Size Analyzer (DLS). The effect of CoNiNAs was investigated based on the amount used in mortar, flexural and compressive strengths of mortar, setting time retarder properties, and carbonation depth measurements of mortars and nanoalloy form based on whether they were solid (chemical synthesise) or liquid (green synthesise). The results revealed that the chemical synthesized CoNiNAs were amorphous metal-metal-oxide complexes with small spherical particles and a low dispersity index, whereas the green synthesized complexes had a more crystalline structure and smaller sizes. The mortar properties were affected by Co and Ni synthesis ratios and addition amounts. The incorporation of CoNiNAs led to an increase in the setting times of mortar. Furthermore, the ‘CN’ 2% sample exhibited the highest compression (49.10±1.19 MPa) and flexural (8.19±0.20 MPa) strengths. In addition, the ‘CN2’ 1% sample exhibited the lowest carbonation depth (2.95±0.35 mm) compared to other samples. Overall, mortars with CoNiNAs additives may be used in high temperature environments, and long shipment times require remote locations due to setting time retarder effect without losing necessary physical properties.

Hyperforin (HPF), the main component responsible for the antidepressant action of Hypericum perforatum, displays additional beneficial properties including anti-inflammatory, antimicrobic, and antitumor activities. Among its antitumor effects, HPF activity on melanoma is poorly documented. Melanoma, especially BRAF-mutated melanoma, is still a high-mortality tumor type and the currently available therapies do not provide solutions. We investigated HPF's antimelanoma effectiveness in A375, FO1 and SK-Mel-28 human BRAF-mutated cell lines. Cell viability assays documented that all melanoma cells were affected by low HPF concentrations (EC50% 2–4 µM) in a time-dependent manner. A Br-deoxy-uridine incorporation assay attested a significant reduction of cell proliferation accompanied by decreased expression of cyclin D1 and A2, CDK4 and of the Rb protein phosphorylation, as assessed by immunoblots. In addition, the expression of P21/waf1 and the activated form of P53 were increased in A375 and SK-Mel-28 cells. Furthermore, HPF exerts cytotoxic effects. Apoptosis is induced 24 h after HPF administration, documented by an increase of cleaved-PARP1 and a decrease of both Bcl2 and Bcl-xL expression levels. Autophagy is induced, attested by an augmented LC3B expression and augmentation of the activated form of AMPK. Moreover, HPF lowers GPX4 enzyme expression, suggesting ferroptosis induction. HPF has been reported to activate the TRPC6 Ca++ channel and/or Ca++ and Zn++ release from mitochondria stores, increasing cytosolic Ca++ and Zn++ concentrations. Our data highlighted that HPF affects many cell-signaling pathways, including signaling induced by Ca++, such as FRA1, pcJun and pCREB, the expression or activity of which are increased shortly after treatment. However, the blockage of the TRPC6 Ca++ channel or the use of Ca++ and Zn++ chelators do not hinder HPF cytostatic/cytotoxic activity, suggesting that damages induced in melanoma cells may pass through other pathways. Remarkably, 24 h after HPF treatment, the expression of activated forms of the transcription factors NF-κB P65 subunit and STAT3 are significantly lowered. Several cytosolic (PGM2, LDHA and pPKM2) and mitochondrial (UQCRC1, COX4 and ATP5B) enzymes are downregulated by HPF treatment, suggesting a generalized reduction of vital functions in melanoma cells. In line with these results is the recognized ability of HPF to affect mitochondrial membrane potential by acting as a protonophore. Finally, HPF can hinder both melanoma cell migration and colony formation in soft agar. In conclusion, we provide evidence of the pleiotropic antitumor effects induced by HPF in melanoma cells. [ABSTRACT FROM AUTHOR]

The plant St. John's wort contains high levels of melatonin, an important biochemical that has both beneficial and adverse effects on stress. Therefore, a method for increasing melatonin levels in plants without adversely affecting their growth is economically important. In this study, we investigated the regulation of melatonin levels in St. John's wort by exposing samples to salinity stress (150 mM) and salicylic acid (0.25 mM) to augment stress tolerance. The results indicated that salinity stress significantly reduced the plant chlorophyll content and damaged the photosystem, plant growth and development. Additionally, these were reconfirmed with biochemical indicators; the levels of abscisic acid (ABA) and proline were increased and the activities of antioxidants were reduced. However, a significant increase was found in melatonin content under salinity stress through upregulation in the relative expression of tryptophan decarboxylase (TDC), tryptamine 5-hydroxylase (T5H), serotonin N-acetyltransferase (SNAT), and N-acetylserotonin methyltransferase (ASMT). The salicylic acid (SA) treatment considerably improved their photosynthetic activity, the maximum photochemical quantum yield (133%), the potential activity of PSⅡ (294%), and the performance index of electron flux to the final PS I electron acceptors (2.4%). On the other hand, SA application reduced ABA levels (32%); enhanced the activity of antioxidant enzymes, such as superoxide dismutase (SOD) (15.4%) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) (120%); and increased polyphenol (6.4%) and flavonoid (75.4%) levels in salinity-stressed St. John's wort plants. Similarly, SA application under NaCl stress significantly modulated the melatonin content in terms of ion balance; the level of melatonin was reduced after SA application on salt-treated seedlings but noticeably higher than on only SA-treated and non-treated seedlings. Moreover, the proline content was reduced considerably and growth parameters, such as plant biomass, shoot length, and chlorophyll content, were enhanced following treatment of salinity-stressed St. John's wort plants with salicylic acid. These findings demonstrate the beneficial impact of salt stress in terms of a cost-effective approach to extract melatonin in larger quantities from St. John's wort. They also suggest the efficiency of salicylic acid in alleviating stress tolerance and promoting growth of St. John's wort plants. [ABSTRACT FROM AUTHOR]

Background: Literature reports randomized trials have examined herbal drugs and other smoking cessation therapies such as aromatherapy acupuncture but no comprehensive overview of the overall results has been provided. The present systematic review and meta-analysis aimed to describe the overall effectiveness and safety of herbal medicines. Methods: This study was conducted from December 2020 to April 2021 by searching seven databases. Herbal drugs have been shown to help people quit smoking in randomized controlled studies. Two teams of researchers independently extracted the data. Findings: A total of 12 trials with 762 smokers were included in this study. The heterogeneity I2 was 43.6% with P = 0.03 (Cochrane Q test) and X2 = 15.77. The overall odds ratio (OR) at 95% confidence interval (CI) was 0.91 (0.68-1.20) which shows a protective factor of herbal preparations and very low heterogeneity. The herbal treatments such as Vernonia cinerea, St. John's Wort, and lavender essential oil were significantly related to a higher continuous abstinence rate (CAR) compared to the controls with risk ratio (RR): 2.13 (0.57-4.61) at week 8; RR: 2.72 (0.77-5.3) at week 12; and RR: 2.77 (0.37-1.13) at week 24. A 7-day point abstinence rate (PAR) at week 8 was RR: 1.24 (0.81-6.34) with 95% CI; RR: 2.09 (0.93-8.29) at week 12, and RR: 2.11 (0.3-3.08) at week 24. Black pepper and lime were better in craving reduction than the placebo group. This study found no significant difference between the treatment and control groups in adverse effects, despite some minor side effects with herbal drugs. Conclusion: The results of this study showed herbal treatments have the potential to help smokers quit the habit. Further welldesigned trials comparing standardized herbal medicines with conventional therapy and placebo are recommended to reinforce this data. [ABSTRACT FROM AUTHOR]

St. John's wort (SJW) is a medicinal herb remedy for mild depression. However, long-term use of SJW has raised safety concerns in clinical practice because of drug-drug interactions. Excessive use of acetaminophen (APAP) causes severe hepatotoxicity, but whether SJW modulates APAP-induced liver injury remains unclear. In this study, the effect of long-term SJW administration on APAP-induced acute hepatotoxicity and the involved mechanisms were investigated. Morphological and biochemical assessments clearly demonstrated that SJW exacerbates APAP-induced toxicity. Moreover, SJW markedly promoted glutathione depletion and increased the levels of the APAP-cysteine and APAP-N-acetylcysteinyl adducts in mice, which enhanced APAP metabolic activation and aggravated APAP-induced liver injury. To further elucidate APAP metabolic activation in liver injury induced by SJW, the activities and expression levels of CYP2E1 and CYP3A were measured. The results showed that the activities and expression levels of CYP2E1 and CYP3A were increased after SJW treatment. Furthermore, the PXR-CYP signaling pathway was activated by SJW, and its downstream target genes were upregulated. Collectively, this study demonstrated that the long-term administration of SJW extract led to the metabolic activation of APAP and significantly exacerbated APAP-induced liver injury, which may suggest caution for the clinical use of SJW and APAP. [ABSTRACT FROM AUTHOR]

We studied the gas chromatographic determination and identification of phenolic compounds in aqueous extracts of St. John's wort (Hypericum perforatum L.) using solid-phase analytical derivatization in the sample preparation for analysis and mass spectrometric detection. A comparative analysis of the results of the determination of phenolic compounds using conventional analytical derivatization in solution and solid-phase analytical derivatization in aqueous extracts of St. John's wort showed that the preparation of derivatives on an adsorbent shortens sample preparation, minimizes the volume of the extract, and expands the list of components to be determined. We found the optimal conditions for the adsorption of phenolic substances from aqueous extracts on the Strata C18-E adsorbent and solid-phase analytical derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide. Gas chromatography–mass spectrometric characteristics were determined to identify compounds in the St. John's wort aqueous extract. The results of the identification of compounds satisfactory agree with the HPLC–DAD data obtained using standard substances, allowing a conclusion that the solid-phase analytical derivatization of phenolic compounds is comparable in analytical capabilities to derivatization in solution. [ABSTRACT FROM AUTHOR]