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The paper considers the antioxidant properties of water and alcohol extractions of fermented and unfermented fireweed of the narrow-leaved fireweed family (Chamerion Angustifolium Onagraceae), St.), bitter wormwood (Artemisia absintium L.), red clover (Trifolium pratense). The effect of the fermentation process, solvent, and extraction time on antioxidant activity (AOA) was studied. A comparative assessment of the antioxidant properties of medicinal plants of the Perm region was carried out. Using the potentiometric method, it was found that the AOA values of water extracts of fireweed angustifolia increase with the time of extraction. Fireweed weakly fermented (finely ground) and fermented (finely ground) have the highest AOA values during extraction within 24 hours. Shoots of young fireweed angustifolia have very low AOA values compared to unfermented and fermented samples. The AOA of aqueous extracts of medicinal plants increases with the time of their extraction. Oregano has the highest AOA value – 2.78×10-2 mol-equiv, and red clover has the lowest value – 0.37×10-2 mol-equiv. The highest value of AOA among mixtures of medicinal plants has a mixture of oregano with fermented fireweed (finely ground) – 2.52×10-2mol-equiv. It has been established that extracts prepared from 40% ethanol solution for fireweed angustifolia and 20 and 40% for oregano have the highest AOA values. The AOA values for the alcohol extract of oregano increase depending on the time of its extraction., В работе рассмотрены антиоксидантные свойства водных и спиртовых экстракций ферментированного и неферментированного кипрея узколистного семейства кипрейные (Chamerion Angustifolium Onagraceae), зверобоя продырявленного (Hypericum perforatum L.), мяты полевой (Mentha arvensis L. s. L.), душицы обыкновенной (Origanum vulgare L.), полыни горькой (Artemisia absintium L.), клевера лугового (Trifolium pratense). Изучено влияние процесса ферментации, растворителя и времени экстракции на антиоксидантную активность (АОА). Проведена сравнительная оценка антиоксидантных свойств лекарственных растений Пермского края. Потенциометрическим методом установлено, что значения АОА водных экстрактов кипрея узколистного увеличиваются от времени экстракции. Кипрей слабоферментированный (мелкоизмельченный) и ферментированный (мелкоизмельченный) имеют наибольшие значения АОА при экстракции в течение 24 ч. Побеги молодого кипрея узколистного обладают очень низкими показателями АОА, по сравнению с неферментированными и ферментированными образцами. АОА водных экстрактов лекарственных растений увеличивается от времени их экстрагирования. Наибольшим значением АОА обладает душица обыкновенная – 2.78×10-2 моль-экв, а наименьшим клевер луговой – 0.37×10-2 моль-экв. Наибольшим значением АОА среди смесей лекарственных растений обладает смесь душицы обыкновенной с кипреем ферментированным (мелкоизмельченным) – 2.52×10-2 моль-экв. Установлено, что наибольшими значениями АОА обладают экстракты, приготовленные из 40% раствора этилового спирта для кипрея узколистного и 20 и 40% – для душицы обыкновенной. Значения АОА для спиртового экстракта душицы увеличиваются в зависимости от времени ее экстрагирования.

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.

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.

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.

St. John’s wort (SJW) has been researched and clinically used for treating various psychiatric disorders, including depression. Few clinical trials have studied its use in smoking cessation. This systematic review provides comprehensive evidence of the studies conducted to date. Five databases were searched for randomized controlled trials (RCTs) that evaluated the effectiveness of SJW for smoking cessation in adults. The trials included the use of SJW alone, or along with nicotine replacement therapy, chromium, or behavioral therapies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to report this systematic review. Overall, four RCTs met the eligibility criteria, and the risk of bias analysis was conducted using the Cochrane criteria. Abstinence, along with other physical symptoms, were measured as outcomes at the end of the follow-up period. Studies reported variable abstinence rates and a decrease in cravings at the end of 12-14 weeks. However, there was minimal to no difference reported between the intervention and placebo groups in all of the clinical trials. One of the studies reported minimal physical side effects. Overall, SJW was well tolerated. Quality analysis of the included studies showed low concerns in two studies while the other two studies showed high concerns in the risk of bias judgment. More clinical trials with larger sample sizes should be conducted in the future to evaluate the effectiveness of the use of SJW for smoking cessation.

In this study, various extracts of Hypericum perforatum L. were investigated in terms of their extraction yields. For this purpose, five solvent systems including 70%EtOH-30% H2O (A), 50%EtOH-50% H2O (B), 30%EtOH-70% H2O (C), 100% EtOH (D), and 100% H2O (E) were used. Ultrasonic-assisted extraction was used for extraction and extraction processes were performed at different temperatures (30°-70oC) and extraction times (30-70 min.). The optimum extraction conditions for H. perforatum was determined based on extraction yield, total phenolic contents, and DPPH radical scavenging activities of the crude extracts, as well. The best ultrasound extraction conditions are achieved in the presence of 70%EtOH-30% H2O solvent system, for 40 min, at 30°C for H. perforatum.

St. John’s wort, a non-FDA-approved over-the-counter (OTC) herbal supplement with antidepressant activity known as Hypericum perforatum, has been found to induce supraventricular tachycardia (SVT) in the absence of any underlying structural cardiac abnormality or known medical history via currently unclear pathophysiology. In this case presentation, the authors present a case of a 33-year-old female who presented with recurrent episodes of palpitations one month after initiating St. John’s wort for the treatment of depression, which ultimately resolved upon cessation of the herbal supplement. Therefore, the postulated insinuating event is suspected to be the ingestion of St. John’s wort. This will be the first documented case of St. John’s wort-induced SVT. This case study brings into question the safety of the use of this agent as an OTC supplement for the management of depression. Further investigation is required to aid in the knowledge and understanding of the causative mechanism and to identify those patients who are at potentially heightened risks of such manifestations.

Little is known about the utilization of St. John’s wort (Hypericum perforatum L.) during pregnancy. In Germany, certain preparations of St. John’s wort can be reimbursed by statutory health insurances, facilitating to investigate exposure to St. John’s wort based on claims data. We therefore aimed to characterize pregnancies exposed to St. John’s wort and to explore potential malformations in the babies. Using claims data from the German Pharmacoepidemiological Research Database (GePaRD), pregnancies exposed to St. John’s wort during at least one trimester between 2006 and 2016 and the corresponding babies were identified. Exposure was identified via outpatient dispensations. Pregnancies were characterized regarding timing of exposure, use of other antidepressants, pregnancy outcomes and the occurrence of major malformations in the babies (not considering codes for musculoskeletal and other malformations due to low data quality in this regard). Out of 496 pregnancies with a dispensation of St. John’s wort during pregnancy, 420 (85 %) had a dispensation during the first trimester. There was a dispensation of other antidepressants before pregnancy in 21 % (during pregnancy: 12 %). Eleven percent of pregnancies ended in non-live births. In 312 babies linked to 305 pregnancies, major malformations were coded in 18 babies (5.8 %), of which 17 were exposed in the first trimester. The crude relative risk of major malformations for babies exposed during the first vs. the second or third trimester only was 3.56 (0.48–26.17). Our results suggest that only in a minority of pregnancies, St. John’s wort is used as an alternative to other antidepressants. Even though the relatively high rates of non-live births and major malformations after exposure to St. John’s wort during the first trimester need to be interpreted with caution, the findings are striking and generate hypotheses that merit further investigation.

26 p.-6 fig.-1 tab.-1 fig supl., Hypericum perforatum L. (St. John’s wort) is a well-known medicinal plant that possesses secondary metabolites with beneficial pharmacological properties. However, improvement in the production of secondary metabolites via genetic manipulation is a challenging task as H. perforatum remains recalcitrant to Agrobacterium tumefaciens-mediated transformation. Here, the transcripts of key genes involved in several plant defence responses (secondary metabolites, RNA silencing, reactive oxygen species (ROS) and specific defence genes) were investigated in H. perforatum suspension cells inoculated with A. tumefaciens by quantitative real-time PCR. Results indicated that key genes from the xanthone, hypericin and melatonin biosynthesis pathways, the ROS-detoxification enzyme HpAOX, as well as the defence genes Hyp-1 and HpPGIP, were all upregulated to rapidly respond to A. tumefaciens elicitation in H. perforatum. By contrast, expression levels of genes involved in hyperforin and flavonoid biosynthesis pathways were markedly downregulated upon A. tumefaciens elicitation. In addition, we compared the expression patterns of key genes in H. perforatum leaf tissues with and without dark glands, a major site of secondary metabolite production. Overall, we provide evidence for the upregulation of several phenylpropanoid pathway genes in response to elicitation by Agrobacterium, suggesting that production of secondary metabolites could modulate H. perforatum recalcitrance to A. tumefaciens-mediated transformation., The author acknowledges the financial support provided by the Fundação para a Ciência e a Tecnologia (FCT) project (PTDC/AGR-GPL/119211/2010), to G.F., grant UID/BIA/04050/2013 (POCI-01-0145FEDER-007569), PhD grant (SFRH/BD/52561/2014), under the Doctoral Programme “Agricultural Production Chains – from fork to farm” (PD/00122/2012) to A.C.P., and by Ministry of Economy and Competitiveness of Spain (grant BIO2016-75619-R [AEI/FEDER, UE]) to F.T.

The rational regulation of programmed cell death by means of autophagy and apoptosis has been considered a potential treatment strategy for cancer. We demonstrated the inhibitory effect of St. John&rsquo, s Wort (SJW) on growth in the triple-negative breast cancer (TNBC) cell line and xenografted mice and its target mechanism concerning autophagic and apoptotic cell death. SJW ethanol extract (SJWE) inhibited proliferation in a dose-dependent manner. SJWE treatment dramatically increased autophagy flux and apoptosis compared with the control. The autophagy inhibitor, 3-methyladenine (3-MA), reversed the SJWE-induced inhibition of cell proliferation and regulation of autophagy and apoptosis, indicating that SJWE induced apoptosis through prodeath autophagy. Furthermore, SJWE inhibited tumor growth and induced autophagy and apoptosis in the tumor of MDA-MB-231 xenografted athymic nude mice. Our results indicate that SJWE might have great potential as a new anticancer therapy for triple-negative breast cancer by inducing prodeath autophagy and apoptosis.

In this study, the effects of treatment with Ag, Au, Cu, Pd, CeO2, CuO, TiO2 and ZnO nanoparticles (NPs) on plant secondary metabolism were tested using an untargeted metabolomic approach in cell suspension cultures of Hypericum perforatum L. Variations in the accumulation of secondary metabolites were observed in cultures after exposure to NPs. Overall, the number of compounds increased by metal NPs was higher than that of metal oxides. Among the metal and metal oxide NPs tested, Ag and CuO respectively induced the greatest changes in secondary metabolism. Ag NPs induced the cellular accumulation of bisxanthone (540.3 fold) gancaonin O (214.2 fold) and fusaroskyrin (98.6 fold). Compounds that were most induced by other NPs were: hyperxanthone C (Au), apigenin (Cu), emodin (Pd), emodin anthrone (CeO2), dihydroxydimethoxyxanthone I (CuO), quercetin (TiO2) and gallic acid (ZnO). The presented results show that the secondary metabolites elicited in H. perforatum vary between the types of NPs.

Objectives: The purpose of this study was to investigate possible protective effects of St. John's wort in the hepatic ischemia/reperfusion injury. Material and Methods: The hepatic artery, portal vein, and bile duct were all clamped for 45 minutes to induce ischemia in rats, and after that reperfusion for 1 hour. SJW was administrated orally, once a day for 3 days before ischemia/reperfusion. The aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and interleukin levels were measured in the serum samples. Luminol chemiluminescence, lucigenin luminol chemiluminescence levels; myeloperoxidase. The sodium-potassium ATPase (Na+/K+ ATPase) activity was determined in the liver tissue, and caspase-3 and caspase-9 activity with the bcl-2/bax ratio were measured by the western blot analysis. Results: The St. John's wort administration recovered the aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and IL-1 beta levels serum parameters meaningfully, while ischemia/reperfusion caused an increase in luminol chemiluminescence, lucigenin luminol chemiluminescence, myeloperoxidase, caspase-3, and caspase-9 activity and led to a decrease in the B-cell lymphoma-2/bcl-2-associated X protein (bcl-2/bax) ratio and the Na+/K+ ATPase activity. Conclusion: The obtained results indicate protective effects of St. John's wort on the ischemia/reperfusion injury through various mechanisms, and we are able to suggest that St. John's wort can clinically create a new therapeutic principle.

With everyday advances in the field of pharmaceuticals, medicinal plants have high priority regarding the introduction of novel synthetic compounds by the usage of environmentally friendly extraction technologies. Herein, a supercritical CO2 extraction method was implemented in the analysis of four plants (chamomile, St. John’s wort, yarrow, and curry plant) after which the non-targeted analysis of the chemical composition, phenolic content, and antioxidant activity was evaluated. The extraction yield was the highest for the chamomile (5%), while moderate yields were obtained for the other three plants. The chemical composition analyzed by gas chromatography-high-resolution mass spectrometry (GC-HRMS) and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) demonstrated extraction of diverse compounds including terpenes and terpenoids, fatty acids, flavonoids and coumarins, functionalized phytosterols, and polyphenols. Voltammetry of microfilm immobilized on a glassy carbon electrode using square-wave voltammetry (SWV) was applied in the analysis of extracts. It was found that antioxidant activity obtained by SWV correlates well to 1,1-diphenyl-2-picrylhidrazine (DPPH) radical assay (R2 = 0.818) and ferric reducing antioxidant power (FRAP) assay (R2 = 0.640), but not to the total phenolic content (R2 = 0.092). Effective results were obtained in terms of activity showing the potential usage of supercritical CO2 extraction to acquire bioactive compounds of interest.

Hypericum perforatum L. is traditionally used as a medicinal plant because of its different bioactive compounds with documented antidepressant and antiinflammatory activities. Plantlets’ mass production with high content of these secondary metabolites has been enhanced through in vitro culture but the process has often been stopped at the multiplication phase. A study was conducted in order to set up an efficient in vitro rooting and acclimatization protocol of a H. perforatum Sicilian genotype well-adapted to south Mediterranean conditions. Aseptic nodal segments were cultured onto a Murashige and Skoog (MS) basal medium supplemented with 4.44 µM 6-benzyladenine for multiplication. Microshoots were then transferred onto specific culture media for in vitro rooting in order to evaluate the nutrients concentration and different auxins effect: full and half-strength hormone-free MS or supplemented with 5.7 µM indole-3-acetic acid (IAA) or 4.9 µM indole-3-butyric acid (IBA). Highest rooting rate was achieved on full-strength MS with IAA 5.7 µM and on all half-strength MS media; higher number of roots was recorded on half-strength MS with IAA and full-strength MS with IBA 4.9 µM; longest roots were measured on full-strength MS with IAA 5.7 µM. Rooted plantlets were ex vitro acclimatized by transferring them into greenhouse in plastic pots filled with peat: perlite and sand: perlite mixtures (1:1, v/v) under mist: acclimatization rate was higher for rooted plantlets grown in sand:perlite substrate.

Rosemary, oregano, pink savory, lemon balm, St. John’s wort, and saffron are common herbs wildly grown and easily cultivated in many countries. All of them are rich in antioxidant compounds that exhibit several biological and health activities. They are commercialized as spices, traditional medicines, or raw materials for the production of essential oils. The whole herbs or the residues of their current use are potential sources for the recovery of natural antioxidant extracts. Finding effective and feasible extraction and purification methods is a major challenge for the industrial production of natural antioxidant extracts. In this respect, the present paper is an extensive literature review of the solvents and extraction methods that have been tested on these herbs. Green solvents and novel extraction methods that can be easily scaled up for industrial application are critically discussed.

Objectives: efficacy and tolerability of WS® 5570 for the treatment of acute mild-to-moderate depression, has been demonstrated in various studies. Here, we present a subgroup analysis of a double blind, randomised trial to compare the therapeutic efficacy of WS® 5570 with paroxetine in patients suffering from a major depressive episode with moderate symptom intensity. Methods: moderate depression was defined by a baseline Hamilton Depression Rating Scale (HAM-D) total score between 22 and 25. Patients received, after a single blind placebo run-in phase of 3–7 d, either 3 × 300 mg/d WS® 5570 or 20 mg/d paroxetine for six weeks. The change of the HAM-D total score was used to describe the efficacy of WS® 5570 compared with paroxetine in the subgroup of patients with moderate depression. Results: the reductions of the HAM-D total score were significantly more pronounced in patients treated with 3 × 300 mg/d WS® 5570 compared to 20 mg/d paroxetine. Conclusions: patients treated with WS® 5570 not only showed a reduction in depression severity score but also yielded greater response and remission rates compared with patients treated with paroxetine. KeypointsVarious studies showed the efficacy and tolerability of WS® 5570 for the treatment of acute mild-to-moderate depression.Beneficial effects of WS® 5570 have been also shown in patients with moderate-to-severe depression.In this study reductions of the HAM-D total score were significantly more pronounced in patients with moderate depression treated with WS® 5570 compared with paroxetine.Patients treated with WS® 5570 not only showed a reduction in depression severity score but also yielded greater response and remission rates compared with patients treated with paroxetine.

St. John's Wort (Hypericum perforatum L.) flowers with 25 g weight and 2.92 moisture on dry basis were dried in microwave oven using 1000, 850, 750, 650, 500, 350, 160 and 90 W microwave output powers and natural drying as a control, until the moisture fell down to 0.07 on dry basis. Drying processes were completed between 2 and 36 min depending on the microwave powers. The values measured were compared with the obtained data using Page's semi-empirical equations. By increasing the microwave output powers, the effective moisture diffusivity values ranged from 2.70 10-09m2s-1 to 1.54 10-10 m2 s-1. Energy consumption remained constant within the power range of 1000-650 W, whereas 500 and 90 W resulted in significant increase in energy consumption. Mean hypericin content values between natural drying and microwave drying with different microwave power varied between 0.241-0.280 %. Maximum hypericin content was observed natural drying (0.280 %), microwave drying of 850 W (0.278 %) and 750 W (0.277 %). The best quality in terms of hypericin content (0.278 %) was obtained in the drying period with 850 W. Microwave power of 850 W for 150 s which were produced the least energy consumption was only 0.06 kWh.

Skrajda-Brdak Marta Natalia. Health benefits of herbal extracts and beverages. Journal of Education, Health and Sport. 2018;8(9):1270-1281 eISNN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.1432862 http://ojs.ukw.edu.pl/index.php/johs/article/view/6066 https://pbn.nauka.gov.pl/sedno-webapp/works/878662 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part b item 1223 (26/01/2017). 1223 Journal of Education, Health and Sport eissn 2391-8306 7 © The Authors 2018; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 02.08.2018. Revised: 18.08.2018. Accepted: 21.09.2018. Health benefits of herbal extracts and beverages Marta Natalia Skrajda-Brdak Chair of Plant Food Chemistry and Processing Faculty of Food Science, University of Warmia and Mazury in Olsztyn University of Warmia and Mazury in Olsztyn Chair of Plant Food Chemistry and Processing Pl. Cieszyński 1, 10-726 Olsztyn e-mail: marta.skrajda@uwm.edu.pl ORCID: 0000-0001-9297-1610 Abstract Introduction: Herbs has been used for thousands of years mainly due to the high content of bioactive compounds. Predominant bioactive compounds of herb extracts and beverages are polyphenols, including phenolic acids and flavonoids. Data shows that antioxidant activity is mostly related to these compounds. Aim: The aim of this work was to provide an overview of health benefits of selected herbal extracts and beverages. Due to large amount of available herbs on the market, only four were chosen and described in details. Results: Based on literature data, depending on the type of the plant and its morphological part different activities occur. Also, the type of extractant and extraction is of great importance. Health benefits of white mulberry, milk thistle, dandelion and ST. John’s wort were described in details. It was indicated that white mulberry show hypoglycemic and hypolipidemic activity, milk thistle and dandelion can be used to treat liver disorders, while St. John’s wort can help with depression. Conclusions: Herbal extracts and beverages can be considered as nutraceuticals due to their positive effect on human health. Keywords: herbal infusions, white mulberry, milk thistle, dandelion, St. John’s wort, phenolic compounds

Hypericum perforatum (HP; also known as St. John’s Wort) is one of the most commonly used herbal therapies in the management of depressive illness. The aim of this study was to evaluate the potential side effects of HP during pregnancy on pregnancy outcome. Using data from the Danish National Birth Cohort (DNBC), we investigated outcomes among 38 HP exposed pregnancies compared to a group of 90,128 women. Associations between HP use and gestational age, preterm birth, birth weight, malformations and Apgar scores were investigated. Preterm birth did not differ across the groups. While the prevalence of malformations in the HP exposed group was slightly higher (8.1%) than observed in the control groups (3.3%; p = 0.13), this was based on only three cases and was not of any specific pattern.

Hypericin (4,5,7,4′,5′,7′-hexahydroxy-2,2′-dimethylnaphtodianthrone) is a naturally occurring chromophore found in some species of the genus Hypericum, especially Hypericum perforatum L. (St. John's wort), and in some basidiomycetes (Dermocybe spp.) or endophytic fungi (Thielavia subthermophila). In recent decades, hypericin has been intensively studied for its broad pharmacological spectrum. Among its antidepressant and light-dependent antiviral actions, hypericin is a powerful natural photosensitizer that is applicable in the photodynamic therapy (PDT) of various oncological diseases. As the accumulation of hypericin is significantly higher in neoplastic tissue than in normal tissue, it can be used in photodynamic diagnosis (PDD) as an effective fluorescence marker for tumor detection and visualization. In addition, light-activated hypericin acts as a strong pro-oxidant agent with antineoplastic and antiangiogenic properties, since it effectively induces the apoptosis, necrosis or autophagy of cancer cells. Moreover, a strong affinity of hypericin for necrotic tissue was discovered. Thus, hypericin and its radiolabeled derivatives have been recently investigated as potential biomarkers for the non-invasive targeting of tissue necrosis in numerous disorders, including solid tumors. On the other hand, several light-independent actions of hypericin have also been described, even though its effects in the dark have not been studied as intensively as those of photoactivated hypericin. Various experimental studies have revealed no cytotoxicity of hypericin in the dark; however, it can serve as a potential antimetastatic and antiangiogenic agent. On the contrary, hypericin can induce the expression of some ABC transporters, which are often associated with the multidrug resistance (MDR) of cancer cells. Moreover, the hypericin-mediated attenuation of the cytotoxicity of some chemotherapeutics was revealed. Therefore, hypericin might represent another St. John's wort metabolite that is potentially responsible for negative herb–drug interactions. The main aim of this review is to summarize the benefits of photoactivated and non-activated hypericin, mainly in preclinical and clinical applications, and to uncover the “dark side” of this secondary metabolite, focusing on MDR mechanisms.

Alternative oxidase (AOX) protein is located in the inner mitochondrial membrane and is encoded in the nuclear genome being involved in plant response upon a diversity of environmental stresses and also in normal plant growth and development. Here we report the characterization of the AOX gene family of Hypericum perforatum L. Two AOX genes were identified, both with a structure of four exons (HpAOX1, acc. KU674355 and HpAOX2, acc. KU674356). High variability was found at the N-terminal region of the protein coincident with the high variability identified at the mitochondrial transit peptide. In silico analysis of regulatory elements located at intronic regions identified putative sequences coding for miRNA precursors and trace elements of a transposon. Simple sequence repeats were also identified. Additionally, the mRNA levels for the HpAOX1 and HpAOX2, along with the ones for the HpGAPA (glyceraldehyde-3-phosphate dehydrogenase A subunit) and the HpCAT1 (catalase 1), were evaluated during the post-germinative development. Gene expression analysis was performed by RT-qPCR with accurate data normalization, pointing out HpHYP1 (chamba phenolic oxidative coupling protein 1) and HpH2A (histone 2A) as the most suitable reference genes (RGs) according to GeNorm algorithm. The HpAOX2 transcript demonstrated larger stability during the process with a slight down-regulation in its expression. Contrarily, HpAOX1 and HpGAPA (the corresponding protein is homolog to the chloroplast isoform involved in the photosynthetic carbon assimilation in other plant species) transcripts showed a marked increase, with a similar expression pattern between them, during the post-germinative development. On the other hand, the HpCAT1 (the corresponding protein is homolog to the major H2O2-scavenging enzyme in other plant species) transcripts showed an opposite behavior with a down-regulation during the process. In summary, our findings, although preliminary, highlight the importance to investigate in more detail the participation of AOX genes during the post-germinative development in H. perforatum, in order to explore their functional role in optimizing photosynthesis and in the control of reactive oxygen species (ROS) levels during the process.

The purpose of this study was to investigate the effects of treatment with water, n-butanol and ether extracts of Hypercom perforatum L. on epileptogenesis in rabbits. Animals from the control group received solvent-ethanol, and the kindling model of epilepsy was used. Epileptic focus was induced in Chinchilla rabbits by stimulation of the hippocampus. The following parameters were determined: the minimum current strength necessary to induce after-discharge (AD) – discharges appearing after cessation of stimulation; AD duration; the number of stimulations necessary to induce spontaneous kindling; and the latency time for the development of full kindling. The results obtained indicate that epileptogenesis is influenced by Hypericum perforatum L. extract treatment. Animals treated with an ether extract of Hypericum perforatum L. required significantly weaker minimum current strengths for the development of epileptogenic focus, and displayed longer AD times, while the number of electro-stimulations necessary for full kindling was less. In contrast, animals treated with water and n-butanol extracts required increased electro-stimulations for the development of epileptic discharge, and displayed shortened AD durations versus controls.

The aim of this study was to investigate the effect of roll compaction variables, various excipients, and tableting speed on the granule and tablet properties made of St. John’s wort dry extract. Three key process variables, such as roll pressure, roll speed, and milling speed were selected and their influences were studied using a factorial design. Bulk and tap density, particle size, tablet hardness and the disintegration time of tablets were significantly affected by these variables. The tablet properties such as hardness and disintegration time were considerably modified using different excipients. The effect of tableting speed on the final tablet hardness was reduced or eliminated by the application of roll compaction compared to direct compaction in the case of plastic material. Roll compaction could be successfully applied as a dry granulation method for St. John’s wort dry extract and it is suggested as a novel choice also for other herbal dry extracts to improve their undesirable properties.

We previously showed that, in vitro, hyperforin from St. John's wort (Hypericum perforatum) inhibits 5-lipoxygenase (5-LO), the key enzyme in leukotriene biosynthesis. Here, we demonstrate that hyperforin possesses a novel and unique molecular pharmacological profile as a 5-LO inhibitor with remarkable efficacy in vivo. Hyperforin (4 mg/kg, i.p.) significantly suppressed leukotriene B(4) formation in pleural exudates of carrageenan-treated rats associated with potent anti-inflammatory effectiveness. Inhibition of 5-LO by hyperforin, but not by the iron-ligand type 5-LO inhibitor BWA4C or the nonredox-type inhibitor ZM230487, was abolished in the presence of phosphatidylcholine and strongly reduced by mutation (W13A-W75A-W102A) of the 5-LO C2-like domain. Moreover, hyperforin impaired the interaction of 5-LO with coactosin-like protein and abrogated 5-LO nuclear membrane translocation in ionomycin-stimulated neutrophils, processes that are typically mediated via the regulatory 5-LO C2-like domain. Together, hyperforin is a novel type of 5-LO inhibitor apparently acting by interference with the C2-like domain, with high effectiveness in vivo.

Bu çalışma, 30 Nisan 2009 tarihleri arasında Antalya[Türkiye]’da düzenlenen 1. International Medicinal and Aromatic Plants Conference on Culinary Herbs’da bildiri olarak sunulmuştur. This research was conducted to investigate effects of morphogenetic and diurnal variability on the hypericin content of St. John's Wort (Hypericum perforatum L.) populations originating from Turkey for maximum utilization of the active substance in plants. During 2002 and 2003, field trials were conducted at Uludag University, Faculty of Agriculture, Department of Field Crops, Bursa. Samples of bud, flower and capsule of H. perforatum L. populations were collected in the second year of cultivation (2003). Factorial arrangements of three H. perforatum L. populations (Bursa, Edirne, Izmir), three part of plant (bud, flower, capsule) and six collection hour (8.00, 10.00, 12.00, 14.00, 16.00, 18.00) were evaluated in a completely randomized design with three replications. Hypericin content (%) in parts of H. perforatum L. populations was determined according to DAC (1986). Consequently, the content of hypericin in the examined populations varied from 0.260% in Bursa to 0.283% in Izmir. Evaluating parts of plant, we also found hypericin content both in floral parts (0.309%) and buds (0.308%) were higher in comparison to capsule tissues (0.208%) for all populations. When collection hours were examined for the hypericin content of plants, the highest content was recorded at 10.00 (0.279%) and the lowest value at 16.00 (0.272%) and 18.00 (0.272%). As a result of this study, it is possible to say that the highest hypericin ratio was determined in flowers and buds generally collected at 8.00 between 10.00 pm with in a day for examined populations.

Gibberella intermedia (Kuhlmann) Samuels et al. (anamorf: Fusarium proliferatum /Matsushima/ Nirenberg) was isolated from seeds of St. John's wort, marshmallow, and coneflower, as well as from roots and stalks of marshmallow and roots of coneflower. These plants had symptoms of leaf chlorosis, malformation, withering and plant dwarfing and were collected from several localities in Serbia during five-year investigations of mycopopulations of the mentioned plants. The morphological characteristics of the pathogen were described.

The study aimed to determine the effect of aqueous extracts of medicinal plants (Matricaria chamomilla, Hypericum perforatum, Achillea millefolium, and Urtica dioica) containing allelopathic compounds on seed germination in lambsquarters (Chenopodium album) and herbicide-resistant windgrass (Apera spica-venti). A Petri-dish experiment was carried out, in which the effects of five concentrations of aqueous extracts on the germination of weeds were assessed for 10 consecutive days. It was found that the dynamics of seed germination are closely related to the type and concentration of aqueous extract of medicinal plants. The 8% U. dioica aqueous extract posed the strongest inhibitory effect, limiting the germination of both lambsquarters and windgrass. Additionally, weed germination was delayed by 12–72 h in the presence of extracts, compared with the control. Summing up, the aqueous extracts of medicinal plants, especially their higher concentrations, pose a desirable inhibiting effect against the germination of lambsquarters and herbicide-resistant windgrass seeds.

WOS: 000233830300022, Of the 57 species of the economically important genus Hypericum (St. John's Wort; Clusiaceae) occurring in China, only a small percentage have been previously phytochemically investigated. As part of our continuing research on the phytochemistry of Hypericum, the chemical compositions of volatiles isolated from 12 Chinese species were determined. Volatile constituents were isolated by microdistillation of dried and ground aerial material from flowering plants and subsequently analyzed by GC/MS. The major component(s) were identified as follows: ar-curcumene (12.6%) and beta-selinene (16.3%) in H. acmosepalum; gamma-murolene (11.3%), beta-selinene (16.3%) and caryophyllene oxide (18.7%) in H. beanii; alpha-terpineol (11.5%) and beta-pinene (29.2%) in H. cal; cis-eudesma-6,11-diene (11.4%) in H. choisyanunt; alpha-pinene (10.4%) and caryophyllene oxide (12.7%) in H. forrestii; cis-beta-guiaene (10.7%) and gamma-muurolene (12.4%) in H. kouytchense; beta-selinene (11.4%) and eudesmadienone (10.8%) in H. lancasteri; cuparene (24.8%) and gamma-muurolene (16.8%) in H. leschenaultii; tricosane (13.3%) and myreene (10.4%) in H. monogynum; P-selinene (14.7%) in H. patulunt; beta-selinene (18.5%) in H. pseudohenryi; and delta-muurolene (10.7%) and delta-cadinene (10.2%) in H. X moserlanum.

53rd Congress of the European-Societies-of-Toxicology (EUROTOX) -- SEP 10-13, 2017 -- Bratislava, Slovakia WOS: 000425486700346 … European Society of Toxicology

Our purpose was to combine the use of morphine with clinically available inhibitors of protein kinase C (PKC), finally potentiating morphine analgesia in humans. Thermal tests were performed in rodents and humans previously administered with acute or chronic morphine combined or not with increasing doses of the PKC-blocker St. John’s Wort (SJW) or its main component hypericin. Phosphorylation of the γ subunit of PKC enzyme was assayed by western blotting in the periaqueductal grey matter (PAG) from rodents co-administered with morphine and hypericin and was prevented in rodent PAG by SJW or hypericin co-administration with morphine, inducing a potentiation of morphine analgesia in thermal pain. The score of pain assessment in healthy volunteers were decreased by 40% when morphine was co-administered with SJW at a dose largely below those used to obtain an antidepressant or analgesic effect in both rodents and humans. The SJW/hypericin potentiating effect lasted in time and preserved morphine analgesia in tolerant mice. Our findings indicate that, in clinical practice, SJW could reduce the dose of morphine obtaining the same analgesic effect. Therefore, SJW and one of its main components, hypericin, appear ideal to potentiate morphine-induced analgesia. Keywords:: morphine, St. John’s wort, protein kinase C, thermal nociception

Biological control agents may have unintended effects on native biota, particularly species that are closely related to the target invader. Here, we explored howChrysolina quadrigemina, a beetle introduced to control the invasive weedHypericum perforatum, impacts nativeH. punctatumin Tompkins County, New York, USA. Using a suite of complementary field surveys and experimental manipulations, we examined beetle preference for native and exoticHypericumspecies and whether beetle herbivory influences the spatial distribution ofH. punctatum. We found that the introduced beetle readily consumes nativeH. punctatumin addition to its intended target, and thatH. punctatumat our field sites generally occurs along forest edges despite higher performance of experimental plants in more open habitats. However, we found no evidence that the beetle limitsH. punctatumto forest edge habitats.

Marshmallow, coneflower, St. John's wort and sage, which grown in plantation, were the hosts of numerous fungi species that cause a variety of symptoms. A total of 34 species from 22 genera were determined. Some species pathogen on only one host (Puccinia malvacearum on marshmallow, Diaporthe eres and Seimatosporium hypericum on St. John's wort), while others were present at all examined hosts (species of the genus Fusarium are present in all examined hosts). The most abundant species in the seed was Alternaria alternate. The percentage of contaminated seeds ranged from 5% to 69%. Fusaium species were isolated from 2.5% to 29% of seeds, depending on the host and year. From the root of the studied medicinal plants seven species of Fusarium (F.graminearum, F. oxysporum, F.proliferatum, F.semitectum, F.solani, F.subglutinans and F.verticilioides) and one of the genus Sclerotinia (S.sclerotiorum) were isolated. Thirteen fungi species belonging to 10 genera were isolated from stem, leaves and flower of medicinal plants. Plantažno gajeni beli slez, ehinacee, kantarion i žalfija su domaćini brojnih vrsta gljiva koje prouzrokuju različite simptome. Ukupno je determinisano 34 vrsta iz 22 roda. Neke vrste parazitiraju samo jednog domaćina (Puccinia malvacearum na belom slezu, Diaporthe eres i Seimatosporium hypericum na kantarionu), dok druge ispoljavaju izrazitu polifagnost (vrste iz roda Fusarium prisutne su na svim ispitivanim domaćinima). Najzastupljenija vrsta na semenu bila je Alternaria alternata, koja je uvek prisutna na semenu u visokom procentu, a pojednih godina i preko 60 %. Procenat kontaminiranog semana kretao se od 5% do 69%. godini. U proseku procenat zaraženog semena sa vrstama roda Fusaium bio 17,2% i kretao se od 2,5% do 29% u zavisnosti od domaćina i godine. Na korenu ispitivanih lekovitih biljaka izolovano je sedam vrsta gljiva iz roda Fusarium (F.graminearum, F.oxysporum, F.proliferatum, F.semitectum, F.solani, F.subglutinans i F verticilioides) i jedna iz roda Sclerotinia (S.sclerotiorum). Sa nadzemnih organa izolovano je 13 vrsta gljiva iz 10 rodova.

Gibberella zeae (anamorph Fusarium graminearum) was determined on seed of St. John's wort produced in localities Pančevo, Gorobilje and Kačarevo during 2008 and 2009. Morphological characteristics of monosporial isolates were described. All tested isolates formed in vitro perithecia, and were classified as F. graminearum (syn. F. graminearum Group 2). Pathogenicity was confirmed by the artificial inoculation of St. John's wort seed. Ispitivanjem zdravstvenog stanja semena kantariona iz kolekcije Instituta za proučavanje lekovitog bilja 'Dr Josif Pančić' proizvedenog tokom 2008. i 2009. godine u lokalitetima Pančevo, Gorobilje i Kačarevo, prvi put je u Srbiji utvrđeno prisustvo vrste Gibberella zeae (anamorf Fusarium graminearum). Ova vrsta je identifikovana na osnovu makroskopskih i mikroskopskih osobina dobijenih monospornih izolata. Svi ispitivani izolati su u in vitro uslovima formirali peritecije, te su na osnovu ovog i drugih osobina identifikovani kao F. graminearum (syn. F. graminearum Grupa 2). Patogenost je potvrđena pojavom nekroze klijanaca nakon inokulacije semena kanatariona.

An immediate demand exists for new tuberculosis (TB) antibiotics due to the ever-increasing spread of drug-resistant strains. The drug-development process goes through four phases, the first (Phase 0) of which is to demonstrate and investigate drug effectiveness and toxicity. This research investigated the effectiveness of the Hypericum perforatum herb (commonly St. John's wort (SJW)) in its growth inhibition of mycobacteria and its viability effect on human lung cells. Organic-solvent SJW extracts were effective at inhibiting every nonpathogenic genetically sequenced Mycobacterium isolate currently available (six isolates) in preliminary studies. Quantitative studies of five Mycobacterium isolates showed an order of concentration sensitivity to the SJW methanol (MeOH) extract as (high to low) M. JLS, M. KMS, M. phlei (not sequenced), M. MCS, B. subtilis, M. smegmatis, and E. coli, with minimal bactericidal concentrations (MBCs) ranging from 0.33-2.66 mg extract/ml. The SJW compounds hyperforin (Hfn), hypericin (Hpn), and pseudohypericin (Phn) were quantified using a novel HPLC method that utilized common HPLC equipment. A crude MeOH extract solution of 133 mg extract/ml contained 2.26 mg Hfn/ml, 0.77 mg Hpn/ml, and 2.67 mg Phn/ml. Purified Hfn had a MBC of between 6-13 μg/ml for M. JLS in the absence of Tween 80. Tween 80 repressed Hfn (46 μg/ml) inhibition of M. JLS at ≥ 0.025% (v/v). Purified Hpn and Phn showed no inhibition of M. JLS at all assayed concentrations, which were ≤ 27 μg/ml and ≤ 25 μg/ml, respectively. Inhibitory results from the five quantitatively assayed Mycobacterium samples could be extrapolated to M. tuberculosis, as these isolates have as high as 72% genetic homology to the pathogen. The crude MeOH extract and Hfn were lethal to the human carcinomic alveolar epithelial lung cell line A549 at 1.3 mg extract/ml (crude extract) and ≥ 11 μg/ml (Hfn), with a Hfn LD50 of 3-6 μg/ml (5.6-11.2 μmol/L). Because Hfn is antiproliferative to a list of other carcinomic cell lines in the same concentration range, the A549 cell line may be added to that list. The addition of M. JLS cells (5x106 cells/cm2) to penicillin-streptomycin-containing A549 culture (which killed the bacteria) did not affect A549 viability.

Gibberella intermedia (Kuhlmann) Samuels et al. (anamorf: Fusarium proliferatum /Matsushima/ Nirenberg) was isolated from seeds of St. John's wort, marshmallow, and coneflower, as well as from roots and stalks of marshmallow and roots of coneflower. These plants had symptoms of leaf chlorosis, malformation, withering and plant dwarfing and were collected from several localities in Serbia during five-year investigations of mycopopulations of the mentioned plants. The morphological characteristics of the pathogen were described. Gibberella intermedia (Kuhlmann) Samuels et al. (anamorf: Fusarium proliferatum /Matsushima/ Nirenberg) je konstatovana na belom slezu, ehinacei i kantarionu i to na semenu, korenu i stablu, kao i na rasadu ehinacea. Osnovni simptom zaraženih biljaka G. intermedia su bili: propadanje klijanaca, trulež korena i korenovog vrata, patuljavost, asimetričan porast, uvelost, hloroza i smežuranost listova. Uzorci zaraženog biljnog materijala bili su poreklom iz okoline Pančeva, Zrenjanina, Banatskog Novog Sela, Inðije, Rume i Stare Pazove. U radu su date morfološke, fiziološke i patogene karakteristike izolata G. intermedia.

This article aims to summarize the current state of knowledge on St. John’s wort (Hypericum perforatum L.) which is one of the oldest and best investigated medicinal herbs. Dried alcoholic extracts are the most important preparations on the market although a variety of other preparations are available. Depressive disorders according to modern diagnostic standards are the best known and most widely investigated indication although the more traditional, broader indication of ‘psycho-vegetative disorders, depressive disorders, anxiety and/or nervous agitation’, including diagnoses such as somatoform disorders, might more adequately describe what Hypericum extracts are actually used for by many practitioners. The exact mechanisms of action are still unclear, but the available research clearly shows that various bioactive constituents contribute to the clinical effects reported, often in a synergistic manner. Hypericum extracts have consistently shown activity in pharmacological models related to antidepressant effects. Randomized clinical trials show that Hypericum extracts are more effective than placebo and similarly effective as standard antidepressants while having better tolerability in the acute treatment of major depressive episodes. The most important risk associated with Hypericum extracts are interactions with other drugs. Therefore, physicians need to be informed whether their patients take St. John’s wort products. If the risk of interactions is adequately taken into account, high quality Hypericum extracts are an effective and safe tool in the hand of qualified health profession-als in primary care.

St. John's Wort (Hypericum perforatum L.) was extracted with supercritical carbon dioxide (SC CO2) under 10, 15 and 20 MPa and at 313 and 323 K. The influence of SC CO2 density (400–800 kg/m3) was examined with respect to extraction yield as well as to hyperforin and adhyperforin content, which was determined using a highly selective LC/MS/MS analytical method. A high concentration (up to 526 mg/g total extract) of two phloroglucinol derivatives was determined in this study showing that the absolute extracted amount of hyperforin and adhyperforin (mg per 1 g of dry plant) is almost constant not depending on total yield of extract, i.e. on density of SC CO2. Determination of the rate of hyperforin and adhyperforin extraction at 313 K and 10 MPa showed that the maximal rates correspond to consumption of 7–8.5 g of CO2 per 1 g of dry St. John's Wort. Investigation of ultrasonic extraction of St. John's Wort followed after pre-treatment of plant material (323 K; 10 MPa; 2 h; without CO2 flow) indicated that obtained extract contains a higher amount (mg/g plant material) of two most important pharmacological active compounds of St. John's Wort, hyperforin and hypericin, than the extract obtained by ultrasonic extraction only.

The present paper reports on the production of anthocyanins and xanthones in different in vitro systems of Hypericum perforatum var. angustifolium (sin. Frohlich) Borkh. Undifferentiated calli and regenerated shoots at different developmental stages were analyzed by applying an extractive and an analytical procedure capable of detecting and quantifying anthocyanins. The findings revealed, for the first time, the co-presence of hypericins and anthocyanins in shoots at initial and more developed stages of H. perforatum var. angustifolium L. Moreover, a high production of xanthones was found in the undifferentiated calli.

In this study, the optimisation of biopharmaceutical properties of a dried commercial extract of St John's Wort were evaluated employing the in vivo forced swimming test (FST). Three new dosage forms containing β-cyclodextrin and surfactants (SDS, ASC8) were compared in the FST with the commercial extract. The commercial extract showed antidepressant activity in mice after 60 min at a dosage of 100 mg/kg. The same antidepressant activity appeared in 30 min with a micellar solution of SDS containing the same quantity of extract (100 mg/kg), while with micelles of ASC8 the effect appeared at 15 min and with a dosage of 30 mg/kg. In the case of β-cyclodextrin the best results were obtained at 30 min, administering 60 mg/kg of the extract. Finally, the influence of the formulations on the water solubility of the constituents of the extract is reported. The tensides dramatically enhanced solubility, in particular that of the more lipophilic compounds, in the case of β-cyclodextrin this effect was very pronounced for flavonoids and biapigenin, lower for hypericins and practically insignificant for hyperforins. Copyright © 2008 John Wiley & Sons, Ltd.

Active phloroglucinol constituents of Hypericum perforatum (St. John's wort) extracts, hyperforin and adhyperforin, have been studied following ion activation using tandem mass spectrometry (MS/MS) and complemented by accurate mass measurements. These two compounds were readily analyzed as protonated and deprotonated molecules with electrospray ionization. MS/MS and MS3 data from a quadrupole-linear ion trap tandem mass spectrometer were employed to elucidate fragmentation pathways. Fourier transform ion cyclotron resonance measurements afforded excellent mass accuracies for the confirmation of elemental formulae of product ions formed via infrared multiphoton dissociation and sustained off-resonance irradiation collision-induced dissociation. Fragmentation schemes have been devised for the dissociation of hyperforin and adhyperforin in negative and positive ion modes. This information is expected to be especially valuable for the characterization of related compounds, such as degradation products, metabolites and novel synthetic analogs of hyperforin. Copyright © 2006 John Wiley & Sons, Ltd.

St. John's Wort, the Hypericum perforatum L. is one of the most analyzed plant species today. Plant was characterized with a wide ecological spectrum and is a plant with beautiful yellow flowers. St. John's Wort was used and still is in used in traditional medicine all over the World. Many bioactive components from St. John's Wort like hypericine, hyperforine, qercetrine and essential oil, were isolated and have been used in medicine. The most popular use of Hipericum extract is as an antidepressant for the medicinal treatment of mild and high depression. The medical use of hyperforine in photodynamic therapy for cancer treatment has now been intensively analyzed. The extract of St. John's Wort showed high antimicrobial, even on pathogenic microorganisms as well as antiviral activity. The use of bioactive components from St. John's Wort depends on the possibility to isolate them in the pure state. It seems that supercritical extraction with carbon dioxide might to be the best solution for obtaining pure extract as well as some of the components present in the essential oil and extract of St. John's Wort. Such a conclusion is supported by the many results of recently performed and published in scientific journals. Kantarion (Hypericum perforatum L.) jedna je od najviše ispitivanih biljnih vrsta. Odlikuje se širokom ekološkom amplitudom i veoma lepom stabljikom sa žutim cvetovima. Kantarion se koristio i koristi u tradicionalnoj medicini širom sveta, a danas kada su izolovane njegove bioaktivne komponente kao što su hipericin, hiperforin, kvercitrin ali i samo etarsko ulje, počeo je da se koristi i u medicini. Najpoznatija je svakako primena ekstrakta kantariona kao antidepresivnog sredstva kod lečenja svih vrsta depresija i uznemirenosti. Primena bioaktivnih komponenti kantariona u medicini kao sredstva za lečenje raka je u razvoju posebno fotodinamička metoda ali se primenjuje kod lečenja raka kože. Ispitana je antimikrobna aktivnost ekstrakta kantariona i njegovih bioaktivnih komponenti i dobijeni su značajni rezultati i na patogene mikroorganizme. Izolovanje bioaktivnih komponenti etarskog ulja ili ekstrakta kantariona koje se mogu upotrebiti u medicinske svrhe moguće je primenom natkritične ekstrakcije tako da su mnoga istraživanja objavljena u literaturi usmerena ka utvrđivanju najboljih uslova ekstrakcije.

St. John's Wort (Hypericum perforatum) is a member of the Hypericaceae family. The genus Hypericum contains around 400 species divided in 30 subgroups that are spread throughout temperate and tropical areas worldwide. More than 70 species have been investigated from a phytochemical viewpoint. H. perforatum is one of the most widely distributed species along with H. crispum and H. hirsutum. This plant, as other members of the Hypericaceae, is a prolific producer of secondary metabolites [I] and has been the topic of numerous phytochemical investigations due its ancient use as a vulnerary and especially, more recently, its widespread application as an antidepressant phytopreparation. Today, the registered phytomedicines consist of an alcoholic extract of the dried flowering tops of the plant. At least height natural product chemical classes are present in this plant; they include naphthodianthrones, phloroglucinols, flavonoids, biflavonoids, xanthones, proanthocyanidins, acid phenols as well as essential oils. Several review have already dealt with the constituents [2-4]. In spite of all the chemical studies performed on this widespread medicinal plant the major limitation to a rational exploitation of this plant is our still-limited knowledge on its active constituents. In this Chapter, a review of the current knowledge of the chemical composition of St. John's Wort is given.

St. John's wort (SJW) has been described to show anti-inflammatory properties due to its inhibitory effects on the expression of pro-inflammatory genes like cyclooxygenase-2, interleukin-6, and inducible nitric-oxide synthase (iNOS). Since iNOS plays a critical role in chronic inflammatory diseases, we have focused our attention on the regulation of iNOS expression by SJW in two different human epithelial cell lines, alveolar A549/8 and colon DLD-1 cells. SJW extract concentration dependently inhibited human iNOS expression evaluated by measuring the amounts of iNOS mRNA, iNOS protein, and NO production in both cell lines. This inhibitory effect resulted from transcriptional inhibition as shown in reporter gene experiments. With electrophoretic mobility shift experiments, we found a SJW-mediated down-regulation of the DNA binding activity of the transcription factor signal transducer and activator of transcription-1alpha (STAT-1alpha), but not of nuclear factor-kappaB. This down-regulation of the STAT-1alpha DNA binding was shown to result from reduced tyrosine phosphorylation of the STAT-1alpha protein. The diminished STAT-1alpha tyrosine phosphorylation resulted from SJW-mediated reduction of Janus kinase 2 activity. These data suggest that extracts from SJW may be a promising anti-inflammatory principle in chronic inflammatory diseases.

Herbal supplements have become increasingly popular in United States during the past decade. This trend begs the question: why are so many people turning to supplements? The increased use of herbal supplementation appears to stem from a public demand for changes in health care. This paper will focus on the regulations placed on the supplement market and the impact that supplementation has on patient care. To illustrate these points, St. John's Wort (SJW) will be examined in detail. Currently regulation in the United States comes from the Food and Drug Administration (FDA) and voluntary organizations within the supplement industry, such as the United States Pharmacopoeia (USP). To many health care providers, these measures do not adequately ensure the safety and efficacy of supplements. Many patients feel that practitioners of conventional medicine do not accept herbal supplements as valid treatment options. Failure to inform a treating physician of supplement use can decrease the effectiveness and safety of total care. All herbal medicines contain more than one active ingredient. Current research lacks necessary information needed to understand how these active ingredients interact with other supplemental and pharmacological preparations. Research conducted on SJW shows that these interactions have severe impact on the quality of overall patient care. The concerns surrounding the herbal industry are profound. Most can be resolved with more research and better regulation.

BACKGROUND/OBJECFTIVES: The effect of St. John’s Wort extract (SJW) on MG-63 cell proliferation and trabecular bone loss induced by ovariectomy was examined. MATERIALS/METHODS: Proliferation, expression of estrogen receptor (ER) α and ER β, and gene expressions of osteoprotegerin (OPG), osteocalcin (OC) and alkaline phosphatase (ALP) were examined in MG-63 cells treated with or without SJW. Ovariectomized rats were treated with SJW at the dose of 100 or 200 mg/kg/day, β-estradiol-3-benzoate (E2), or vehicle only (OVX-C), and sham operated rats were treated with vehicle only (Sham-C). Serum ALP and C-telopeptide (CTX), and femoral trabecular bone loss were examined. RESULTS: SJW increased MG-63 cell proliferation and expression of ER α and ER β, and positive effect was shown on gene expressions of ALP, OC and OPG. SJW also showed estrogen like effect on bone associated with slowing down in trabecular bone loss. Histopathology by H&E showed rats treated with SJW displayed denser structure in metaphyseal region of distal femur compared with rats in OVX-C. SJW was shown to reduce serum CTX in OVX rats. CONCLUSION: The present study provides new insight in preventing estrogen deficiency induced bone loss of SJW and possibility for its application in bone health supplement.

Hypericum perforatum L. and Achillea millefolium L. are plants which can be characterized as heavy metal accumulators. Including relating soils samples differing in pH reaction, 14 samples of St. John’s wort and 9 samples of yarrow were collected from different localities in Yugoslavia and Republic Srpska. The total heavy metal content (Mn, Zn, Cu, Pb, Ni and Cd) was determined in the collected herb material (for St. John’s wort – 25 cm from the top of plant and for yarrow – 30 cm) by standard analytical methods. Heavy metal content in the herb mostly dependent on soil composition, for both species. Concentration of Mn and Zn in the herb decreased linearly with the increase of soil pH (Mn: r = 0.62* for yarrow and r = 0.66* for St. John’s wort; Zn: r = 0.71* for yarrow and r = 0.62* for St. John’s wort), while Cd concentration decreased exponentially (r = 0.77* for yarrow and r = 0.58* for St. John’s wort). Cd content in St. John’s wort was mostly above limit of 0.5 ppm when soil pH (in nKCl) was lower than 5.9, and 4.5 for yarrow. Higher Cd content in the yarrow herb, and especially St. John’s wort herb from acidic soils, points to significance of: 1. Required control of Cd content in the raw materials collected in the wild and 2. Necessary avoidance of such soils for cultivated production of those species. A relationship of Ni content in the herb with soil pH was found only for St. John’s wort (r = 0.80***). Correlation between heavy metal content in the herb and humus content in the soil was analyzed but statistically significant regression coefficients were not obtained. Positive linear dependence was found between Pb and Ni content in the herb and their total content in the soil, for Achillea millefolium L. (r = 0.88** and r = 0.65*, respectively), which can be explained by the origin of the samples. Also, there is increase of Cu, Pb and Ni content in the yarrow herb with the increase of their available content in the soil (r = 0.67*, r = 0.88**, r = 0.65 *, respectively), while such dependence was obtained only for Pb content in St. John’s wort herb (0.56*). INTRODUCTION Harmful accumulation of heavy metals in plants has lately become more frequent in agricultural ecosystems, especially the accumulation of cadmium (Cd), lead (Pb), chromium (Cr), mercury (Hg) and nickel (Ni). These are mostly elements that have been shown to be non-essential to plants. Their uptake is governed by the genetic characteristic of particular species and by the soil properties. Higher amounts of heavy metals entering the food chain could, eventually, be harmful to humans and animals. The better knowledge of factors affecting the uptake and accumulation of heavy metals in some species is especially important for the cultivation of medicinal plants. Hypericum perforatum L. and Achillea millefolium L. are plants which have been characterized as heavy metal accumulators (Schneider and Marquard, 1996). Elevated contents of Cd, Ni and Pb in numerous samples of St. John’s wort and yarrow, from bothretail trade and wild habitats, have been revealed in earlier research in our country (Radanovic et al., 2000). Proc. Int. Conf. on MAP Eds. J. Bernath et al. Acta Hort. 576, ISHS 2002 296 Therefore, the applied agro technique during the growth of these species must provide the minimum uptake of potentially harmful elements. Heavy metal uptake by plants is a complex process, governed by the numerous factors influencing each other: plant species, genotype, availability and mobility of the metals in a soil, and soil properties, such as: pH, organic matter, clay content, rH, etc. (Marchner, 1986, KabataPendias and Pendias, 1992, Alloway, 1995). Knowledge of the influence of soil properties on the heavy metal uptake could be very useful when a choice of growing site or possible agrotechniques are issued for cultivation of these plants. MATERIALS AND METHODS Material. Plant material for this research was collected in the wild during the growing season 1999 in Yugoslavia and Republic Srpska. Samples of Hypericum perforatum L. were collected at 11 different sites, while samples of Achillea millefolium L. originated from 9 localities. An additional three Hypericum samples came from cultivated production. Along with herb samples, corresponding soil samples were also taken. Plant Analyses. Herb samples were dried at 70 C and ground. Wet digestion was done in the mixture of acids: HNO3 + HClO4, with the addition of H2O2. Heavy metal content (Mn, Zn, Cu, Pb, Ni, Cd) was measured by flame AAS. Soil Analyses. In the air-dried soil samples, crushed in the porcelain mortar to pass a 2 mm sieve, the following properties were determined: pH (in H2O and n KCl); humus content; total heavy metal content (by AAS, after digestion in HNO3 + H2O2) and available heavy metal content (by AAS, after extraction with 0.005 M DTPA). Relationships between heavy metal content in the herb and soil properties were determined by statistical analysis (correlation and regression coefficients). RESULTS AND DISCUSSION Main soil chemical characteristics as well as heavy metal content in soil and plant material are shown in Tables 1 and 2. Heavy metal content in the herb mostly depended on soil reaction, for both analyzed species. Concentration of Mn, Zn and Ni in the herb decreased linearly with the increase of soil pH, while Cd concentration decreased exponentially (Table 3.). Exponential dependence found for Cd refers to the greater influence of soil pH on the Cd uptake, as compared with other investigated elements. Cd content in St. John’s wort was mostly above limit of 0.5 ppm (Schiller, 1994) when soil pH (in n KCl) was lower than 5.9 (Fig. 1). For yarrow, Cd content in the herb was above limit (0.3 ppm) when soil pH (in n KCl) was lower than 5.1 (Fig. 2). According to the results of this research, St. John’s wort has higher potential for Cd uptake, compared with yarrow, at the same pH and Cd content in the soil. When growing sites for these species are considered, soil pH is most important limiting factor, especially for St. John’s wort growth, since higher Cd concentration in its herb could be found on the soils with relative high pH reaction. Higher Cd content in the yarrow herb and especially St. John’s wort herb from acid soils points to the necessity of: 1. permanent control of Cd content in the raw materials collected in the wild, 2. avoidance of such soils for cultivated production of those species. Dependence of Ni content in the herb on soil pH was found for St. John’s wort (r = -0.80 ***), since Ni content in the herb was higher than its natural level for plant material (0.1 – 5 ppm, Hutchinson, 1981) when soil pH was less than 5.5 (Fig. 3.). That is in agreement with the well-known fact that available amounts of Ni are higher in the acid soils (Adriano, 1986, Alloway, 1995). For yarrow, dependence of Ni content in the herb on soil pH wasn’t obtained, although Ni content in almost all analyzed plant samples was higher then 5 ppm. The higher content of this element in plants was found even at soil pH > 7.0, which points to the greater influence of genetic tendency of that species for Ni uptake, comparing with soil composition. Content of Mn and Zn in both analyzed species had negative correlation

In the present study, the effects of Hypericum perforatum on nicotine-induced locomotor activity have been investigated in mice. Adult male Swiss-Webster mice were subjects. Nicotine (0.5, 1 and 2 mg/kg) and saline were given to mice intraperitoneally. Locomotor activities of the mice were recorded for 30 min immediately following nicotine or saline administration. Hypericum perforatum extract (HPE) (6, 12, 24 and 48 mg/kg) and saline were injected to another five independent groups of the mice and 20 min later, locomotor activity was recorded for 30 min. In further study, HPE (6-24 mg/kg) was administered to other independent groups of mice 20 min before nicotine (1 mg/kg) injections and locomotor activity was recorded for 30 min immediately after nicotine administration. Nicotine (1 mg/kg) produced a significant increase in locomotor activity of the mice. HPE depressed significantly locomotor activity of the mice at dose of 48 mg/kg. Other doses of HPE (6-24 mg/kg) did not produce any significant change in the locomotor activities. HPE (24 mg/kg) blocked significantly nicotine (1 mg/kg)-induced locomotor. Our results suggest that HPE blocks nicotine-induced locomotor hyperactivity in mice. Thus, it may be a useful agent for treatment of nicotine-type dependence. Özet Sunulan çalismada, farelerde nikotin ile indüklenen lokomotor aktivite üzerine Hiperikum perforatum ekstresinin etkileri incelenmistir. Çalismada denek olarak eriskin erkek Swiss-Webster türü fareler kullanildi. Nikotin (0.5, 1 ve 2 mg/kg) ve serum fizyolojik farelere intraperitoneal yoldan enjekte edildi. Nikotin veya salin enjeksiyonlarindan hemen sonra 30 dakika süre ile farelerin lokomotor aktiviteleri kaydedildi. Hiperikum perforatum ekstresi (HPE) (6, 12, 24 ve 48 mg/kg) ve salin diger 5 farkli grup fareye enjekte edildi ve enjeksiyonlardan 20 dakika sonra farelerin 30 dakika süre ile lokomotor aktiviteleri kaydedildi. Daha ileri bir çalisma olarak, HPE (6-24 mg/kg) baska bagimsiz gruplarda yer alan farelere nikotin (1 mg/kg) enjeksiyonundan 20 dakika önce verildi. Bu gruplarda da nikotin (1 mg/ kg) enjeksiyonlarinin hemen sonrasinda farelerin 30 dakika süre ile lokomotor aktiviteleri kaydedildi. Nikotin (1 mg/kg) farelerin lokomotor aktivitelerinde anlamli ölçüde artisa neden oldu. HPE 48 mg/kg’lik dozunda farelerin lokomotor aktivitesini anlamli ölçüde deprese etti. HPE’nin çalismada kullanilan diger dozlari (6-24 mg/kg) lokomotor aktivitelerde anlamli bir degisiklik olusturmadi. HPE (24 mg/kg) nikotin ile indüklenen lokomotor aktivite artisini anlamli ölçüde bloke etti. Sonuçlarimiz HPE’nin farelerde nikotin ile indüklenen lokomotor aktivite artisini bloke ettigine ve bu ekstrenin nikotin tipi bagimliligin tedavisinde faydali olabiecegine isaret etmektedir.

WOS: 000274581600076, The essential oil obtained by hydrodistillation of Hypericum perforatum L. (Clusiaceae) obtained from Turkey was analyzed by gas chromatography and gas chromatography/mass spectrometry (GC/MS), simultaneously. Main constituents of the oil was found as germacrene D (23 %), beta-caryophyllene (14 %), bicyclogermacrene (5 %), caryophyllene oxide (4 %) and spathulenol (4 %). the essential oil was also screened for its anticandidal properties against various Candida species.

We studied the anticonvulsant activity of the aqueous and ethanolic extracts of Hypericum perforatum aerial parts in mice. The pentylenetetrazole (PTZ) and the maximal electroshock seizure (MES) tests were used for assessing the anticonvulsive effects of this plant. In the PTZ test, the extracts (0.1-1 g/kg, i.p.) delayed the onset of tonic convulsions and protected mice against mortality. In the MES test, both extracts did not show antiseizure activity. L-NAME (1-10 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, reduced the anticonvulsant activity of the extracts. The results of this study indicate that the extracts of H. perforatum aerial parts could contribute to the control of petit mal seizure and this effect may be partially mediated by nitric oxide pathway.