Study on the protective effect of Hypericum perforatum on cerebral ischemia-reperfusion injury in rats and its mechanism / 中国药房

OBJECTIVE To study the protective effect and potential mechanism of Hypericum perforatum on cerebral ischemia- reperfusion in rats. METHODS The male SD rats were randomly divided into sham operation group， model group， positive control group （nimodipine 0.012 g/kg）， H. perforatum high-dose and low-dose groups （5.212， 1.303 g/kg）， with 10 rats in each group. Except for sham operation group， the left middle cerebral artery ischemia-reperfusion model was established with the modified suture method. Administration groups were given relevant medicine intragastrically since the second day after surgery， once a day， for 7 consecutive days. The neurological function scores of rats were measured before drug intervention （the first day after modeling） and after the last administration， and the cerebral infarction after the last administration was observed using TTC staining method；HE staining and TUNEL staining methods were used to observe the pathological changes of the cerebral cortex and hippocampus， and the apoptosis of nerve cells， respectively. Western blot and RT-PCR were used to observe the protein and mRNA expressions of erythropoietin （EPO）， erythropoietin receptor （EPOR）， Janus kinase 2 （JAK2） and signal transduction and activator of transcription 3 （STAT3）， and protein expression of phosphorylated STAT3 （p-STAT3）， respectively. RESULTS Compared with sham operation group， neurological function score and the proportion of cerebral infarction in model group were significantly increased before intervention and after the last administration （P＜0.01）， with significant damage to nerve cells in cerebral cortex and hippocampus， an increase in apoptotic nerve cells， and a significant increase in apoptosis rate （P＜0.01）； protein and mRNA expressions of EPO and EPOR in the brain tissue were significantly reduced （P＜0.01）， while the protein expressions of JAK2， p- STAT3 and STAT3， and mRNA expressions of JAK2 and STAT3 were significantly increased （P＜0.01）. Compared with model group， the damage and apoptosis of nerve cells in cerebral cortex and hippocampus of rats in administration groups were improved， and the quantitative indicators were almost significantly improved （P＜0.05 or P＜0.01）. CONCLUSIONS H. perforatum has a protective effect against cerebral ischemia-reperfusion injury in rats， and the related mechanism may be related to the regulation of EPO-mediated JAK2/STAT3 signaling pathway.

Mechanism of Ficus hirta-Hypericum perforatum in treatment of microvascular angina based on network pharmacology and molecular docking / 中国中药杂志

The active ingredients of Ficus hirta and Hypericum perforatum were collected from Traditional Chinese Medicine Database and Analysis Platform(TCMSP) and related papers. The potential targets of these two medicinal herbs were searched from HERB database, and those associated with microvascular angina were screened out from GeneCards, Online Mendelian Inheritance in Man(OMIM), Therapeutic Target Database(TTD), and HERB. Cytoscape was used to construct a protein-protein interaction(PPI) network of the common targets shared by the two herbs and microvascular angina based on the data of String platform. Metascape was employed to identify the involved biological processes and pathways enriched with the common targets. Cytoscape was used to draw the "active ingredient-target-pathway" network. AutoDock Vina was used to dock the core ingredients with the key targets. A total of 19 potential active ingredients and 71 potential targets were identified to be associated with microvascular angina. Bioinformatics analysis showed that phosphatidylinositol-3-kinase/protein kinase B(PI3 K-AKT), interleukin-17(IL17), hypoxia-inducible factor 1(HIF-1) and other signaling pathways were related to the treatment of microvascular angina by F. hirta and H. perforatum. Molecular docking results showed that β-sitosterol, luteolin and other ingredients had strong affinity with multiple targets including mitogen-associated protein kinase 1(MAPK1), epidermal growth factor receptor(EGFR) and so on. These findings indicated that F. hirta and H. perforatum may regulate PI3 K-AKT, IL17, HIF-1 and other signaling pathways by acting on multiple targets to alleviate oxidative stress, inhibit inflammatory response, regulate angiogenesis, and improve vascular endothelium and other functions. This study provides reference for in vitro and in vivo studies of the treatment of microvascular angina.

Retrospective cost-utility and budget impact assessments of Hypericum perforatum in contrast with Fluoxetine treatment for depression in Karachi, Pakistan

In this study we have compared two different types of therapies i.e. herbal and allopathic system of therapies for Depression and studied them from the social perspectives. The Hypericum perforatum is compared with Fluoxetine [HCL] in terms of cost-utility and financial savings thereby evaluating its influence on annual expenditure of depressive patients that were randomly selected from 178 union councils of the city of Karachi, Pakistan. For both system of therapies a total of 356 patients were selected by stratified random sampling. Taking frequency of depression as '1' annually with discount rate at 3% for calculating the burden-of-illness in terms of disability-adjusted-life-years. The cost-utility and the budget-impact assessments were carried out to assess incremental-cost-effectiveness-ratio, and the budget-impact-per-onset as well as budget-impact-per-year values. In comparison with the Fluoxetine therapy, the Hypericum perforatum was found to relieve symptoms in 21.47% less cost; owing 29.23% less disability-adjusted-life-years and 21.45% less budget-impact-per-onset as well as budget-impact-per-year. The annual mean incremental-cost-effectiveness-ratio was found to be at 36.95±270.74 (less than GDP per capita threshold of Rs. 38,173.02). Hypericum perforatum provide the optimal utility with less impact on budget of a patient in comparison with the treatment of symptoms of depression with Fluoxetine.

Effect of Hypericum Perforatum L Extracts on depression induced by chronic unpredictable mild stress in mice / 中华行为医学与脑科学杂志

Objective@#To observe the improving effect of Hypericum Perforatum L Extracts (HPLES)on depression induced by chronic unpredictable mild stress in mice.@*Methods@#The depression model was established by the method of chronic unpredictable mild stress. Fifty depression model mice were divided into model control group, fluoxetine hydrochloride group (2.6 mg / kg), Hypericum perforatum extract low, medium and high (0.2 g / kg, 0.4 g / kg, 0.8 g / kg) dose groups according to the random number table method. Another 10 normal mice matched with body weight were taken as the normal control group. The mice in normal control group and the model control group were given pure water by gavage every day, and the mice in other groups were given corresponding solution by gavage for 4 weeks. In addition to the normal control group, the mice in other groups continued to undergo chronic unpredictable mild stress during gavage.The sugar water preference test and forced swimming test were performed after the last administration. Blood samples were collected from the posterior orbital venous plexus, and the levels of dopamine (DA) and brain-derived neurotrophic factor (BDNF) were measured by Elisa. The hippocampal tissues of mice were examined by HE staining.@*Results@#Compared with the normal control group, the body mass of mice in the model control group decreased significantly at the first, second, third and fourth weeks (t=2.739, 4.162, 4.082, 3.957; all P<0.05). At the first, second, third and fourth weeks, the body mass of mice in the low, middle and high dose group of Hypericum perforatum extract were not significantly different from those in the model control group (all P>0.05). Compared with the normal control group, the sugar water preference index of mice in the model control group was significantly reduced((61.3±4.5)%, (52.6±5.2)%; t=2.721, P<0.05), the swimming immobility time was prolonged((44.3±20.00) s, (101.8±50.8) s; t=2.939, P<0.05), the difference were statistically significant. Compared with the model control group, the sugar water preference index of mice in the low, middle and high dose group of Hypericum perforatum extract increased((61.8±4.7)%, (65.2±4.1)%, (62.6±5.6)%, t=-3.005, 5.073, -2.928, all P<0.05), the swimming immobility time decreased ((47.2±17.9) s, (54.8±50.3) s, (61.3±44.2) s; t=2.803, 1.921, 1.903, all P<0.05). The results of Elisa showed that compared with the normal control group, the levels of serum DA and BDNF of mice in the model control group were significantly lower (t=3.031, 8.507, all P<0.05); compared with the model control group, the levels of serum DA of mice in the low dose and high dose group of Hypericum perforatum were significantly higher (t=5.025, 3.414, P<0.05), and the serum BDNF of mice in the high dose group of Hypericum perforatum was also significantly higher (t=6.098, P<0.05), the difference was statistically significant. HE staining showed that compared with the normal control group, the neurons in CA3 area of hippocampus in the model control group mice were seriously damaged, suggesting the establishment of the mouse model. Compared with the model control group, the atrophy and degeneration of hippocampal CA3 cells in the three dose groups were significantly reduced. The atrophy and deformation of hippocampal CA3 neurons in the low, middle and high dose groups of Hypericum perforatum extract were relieved.@*Conclusion@#HPLES have obvious improving and antidepressant effects on the depression model mice induced by chronic unpredictable stress.The above effects may be related to the improvement of serum DA, DBNF level and reduce neuronal damage in CA3 area.

Effect of Hypericum Perforatum L Extracts on depression induced by chronic unpredictable mild stress in mice / 中华行为医学与脑科学杂志

Objective To observe the improving effect of Hypericum Perforatum L Extracts (HPLES)on depression induced by chronic unpredictable mild stress in mice. Methods The depression model was established by the method of chronic unpredictable mild stress. Fifty depression model mice were divided into model control group,fluoxetine hydrochloride group (2. 6 mg / kg),Hypericum perforatum ex-tract low,medium and high (0. 2 g / kg,0. 4 g / kg,0. 8 g / kg) dose groups according to the random num-ber table method. Another 10 normal mice matched with body weight were taken as the normal control group. The mice in normal control group and the model control group were given pure water by gavage every day,and the mice in other groups were given corresponding solution by gavage for 4 weeks. In addition to the normal control group,the mice in other groups continued to undergo chronic unpredictable mild stress during gavage. The sugar water preference test and forced swimming test were performed after the last administration. Blood samples were collected from the posterior orbital venous plexus,and the levels of dopamine (DA) and brain-derived neurotrophic factor (BDNF) were measured by Elisa. The hippocampal tissues of mice were exam-ined by HE staining. Results Compared with the normal control group,the body mass of mice in the model control group decreased significantly at the first,second,third and fourth weeks ( t=2. 739,4. 162,4. 082, 3. 957;all P<0. 05). At the first,second,third and fourth weeks,the body mass of mice in the low,middle and high dose group of Hypericum perforatum extract were not significantly different from those in the model control group (all P>0. 05). Compared with the normal control group,the sugar water preference index of mice in the model control group was significantly reduced((61. 3± 4. 5)%,(52. 6± 5. 2)%; t=2. 721,P<0. 05),the swimming immobility time was prolonged(( 44. 3± 20. 00) s,(101. 8± 50. 8) s;t=2. 939,P<0. 05),the difference were statistically significant. Compared with the model control group,the sugar water preference index of mice in the low,middle and high dose group of Hypericum perforatum extract increased ((61. 8±4. 7)%,(65. 2±4. 1)%,(62. 6±5. 6)%,t=-3. 005,5. 073,-2. 928,all P<0. 05),the swimming immobility time decreased ((47. 2±17. 9) s,(54. 8±50. 3) s,(61. 3±44. 2) s; t=2. 803,1. 921,1. 903,all P<0. 05). The results of Elisa showed that compared with the normal control group,the levels of serum DA and BDNF of mice in the model control group were significantly lower (t=3. 031,8. 507,all P<0. 05); com-pared with the model control group,the levels of serum DA of mice in the low dose and high dose group of Hypericum perforatum were significantly higher (t=5. 025,3. 414,P<0. 05),and the serum BDNF of mice in the high dose group of Hypericum perforatum was also significantly higher (t=6. 098,P<0. 05),the differ-ence was statistically significant. HE staining showed that compared with the normal control group,the neu-rons in CA3 area of hippocampus in the model control group mice were seriously damaged,suggesting the es-tablishment of the mouse model. Compared with the model control group,the atrophy and degeneration of hippocampal CA3 cells in the three dose groups were significantly reduced. The atrophy and deformation of hippocampal CA3 neurons in the low,middle and high dose groups of Hypericum perforatum extract were re-lieved. Conclusion HPLES have obvious improving and antidepressant effects on the depression model mice induced by chronic unpredictable stress. The above effects may be related to the improvement of serum DA,DBNF level and reduce neuronal damage in CA3 area.

A new 2,3-dioxoflavonoid from the aerial part of Hypericum perforatum / 药学学报

Phytochemical study of the aerial parts of Hypericum perforatum L. resulted in the isolation of an undescribed compound, which was identified as Rel-(2S,3R)-2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-2-methoxy-3-(2-oxopropyl)chroman-4-one (1) by spectroscopic methods including UV, IR, HR-ESI-MS, 1D and 2D NMR spectra. Compound 1 is a new 2,3-dioxo-flavone with an acetonyl moiety, rarely found in nature. In addition, a plausible biogenetic pathway of 1 was proposed in this article.

Hypericum perforatum chronic treatment affects cognitive parameters and brain neurotrophic factor levels

Objective: To evaluate the effects of Hypericum perforatum (hypericum) on cognitive behavior and neurotrophic factor levels in the brain of male and female rats. Methods: Male and female Wistar rats were treated with hypericum or water during 28 days by gavage. The animals were then subjected to the open-field test, novel object recognition and step-down inhibitory avoidance test. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) levels were evaluated in the hippocampus and frontal cortex. Results: Hypericum impaired the acquisition of short- and long-term aversive memory in male rats, evaluated in the inhibitory avoidance test. Female rats had no immediate memory acquisition and decreased short-term memory acquisition in the inhibitory avoidance test. Hypericum also decreased the recognition index of male rats in the object recognition test. Female rats did not recognize the new object in either the short-term or the long-term memory tasks. Hypericum decreased BDNF in the hippocampus of male and female rats. Hypericum also decreased NGF in the hippocampus of female rats. Conclusions: The long-term administration of hypericum appears to cause significant cognitive impairment in rats, possibly through a reduction in the levels of neurotrophic factors. This effect was more expressive in females than in males.

Improvement effect of extract of St.John's wort tabIets on fear and anxiety behavior of post-traumatic stress disorder model mice / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of extract of St.John's wort tablets (ESJWT) on post-traumatic stress disorder (PTSD) in a mouse model and explore possible avenues for the treat-ment of PTSD.METHODS Forty-eight C57BL/6 male mice were randomly divided into 4 groups:normal control group, model group, sertraline and ESJWT treatment groups, with 12 mice in each group. Except the normal control group, all the mice were treated with fifteen intermittent inescapable foot-shocks (intensity:0.8 mA;interval:10 s;duration:10 s)for 2 d.Sertraline 15 mg·kg-1and ESJWT 25 mg·kg-1 were ig given one hour before foot-shocks repectively,once a day,for 18 d.Then,contextual freezing and fecal pellet were tested on the 3rd,8thand 15thdays.In addition,open field test,elevated plus maze test and staircase test were performed on the 16th, 17thand18thdays, respectively. Here, the day mice were subjected to short foot-shocks was defined as the 1stday.The serum contents of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) were evaluated using ELISA after behavior tests. RESULTS Compared with normal control group, the freezing time and the number of fecal pellet in model group were significantly increased(P<0.01).Meanwhile,the time and number of entries into the central open field and open arm were decreased(P<0.01).The above experiments indicated that the mouse model of PTSD was established successfully. Compared with model group, both sertraline and ESJWT extract showed anti-PTSD effect, with the decreased percentage of freezing time (P<0.05, P<0.01). ESJWT extract treatment also reduced the amount of fecal pellet(P<0.01).However,no significant changes of the contents of NE and 5-HT in any group were seen.CONCLUSION ESJWT has anti-PTSD effect in the mouse model,which might be used for the treatment of PTSD.

Chemical constituents of Hypericum perforatum / 中国中药杂志

A chemical investigation on the aerial parts of Hypericum perforatum resulted in the isolation of a new phloroglucinol derivatives (1), and seven known compounds (2-8). The structures of the compounds were elucidated by means of spectroscopic methods (MS, IR, 1D NMR, and 2D NMR) as 3-methyl-4,6-di (3- methyl-2-butenyl)-3-(4-methyl-3-pentenyl)-2-(2-ethyl-1-oxobutyl)-cyclohexanone (1)，hyperforin (2)，(2R,3R,4S,6)-3-methyl-4,6-di(3-methyl-2-butenyl)-2-(2-methyl-1-oxo-propyl)-3-(4-methyl-3-pentenyl)-cyclohexanone (3)，hyperscabrin B (4)，hyperscabrin C (5)，furohyperforin isomer 1 (6)，furoadhyperforin (7)，and furohyperforin (8). Compound 1 was a new compound, and compounds 3-5 were obtained from H. perforatum for the first time.

Un caso clínico de fractura dental y su abordaje clínico homeopático / A clinical case of dental fracture and its clinical homeopathic approach

Se presenta un caso de trauma dentoalveolar en un paciente masculino de 22 años de edad, al sufrir un asalto en la Ciudad de México. El paciente acude al consultorio dental 29 horas posteriores al incidente; durante la exploración se identifican edema y laceraciones en los labios; movilidad de los dientes centrales superiores y fractura del ángulo mesio-incisal del lateral superior derecho. El estudio radiográfico muestra fractura de las coronas en los centrales superiores. El abordaje terapéutico combinó Homeopatía, tratamiento endodóntico, periodontal y prótesis. Los medicamentos que se administraron fueron: Arnica montana, Hypericum perforatum, Calendula officinalis y Echinacea angustifolia (nombre de marca: Gavosim); se prescindió de antibióticos y antiinflamatorios. A las cuatro semanas del tratamiento endodóntico se remitió al paciente con el periodoncista, y cuatro semanas después, con el protesista. Al final, se logró la rehabilitación total. Se concluye que los medicamentos prescritos facilitaron la recuperación de los tejidos periodontales.

In vitro Bacteriostatic Effect of a Scaffold with a Mixture of Hypericum perforatum and Azadirachta indica Oil Extracts.

Background: Clinical evidences suggest antimicrobial activities of a new oil extract mixture of Hypericum perforatum and Azadirachta indica, included in a polymeric scaffold (or Hyperoil™ Polimeric Substrate - HPS). Methods: Bacteriostatic activity was investigated on selected strains of Staphylococcus aureus (ATCC® 12598™), Pseudomonas aeruginosa (ATCC® 10145™) and Klebsiella ozaenae AM through standardized in vitro tests. Results and Conclusion: All bacterial strains were stabilized or reduced in size after 3 and 24 hours contact with the HPS if compared to the empty polymeric scaffolds. Results showed the bacteriostatic effect of HPS that, added with its anti-inflammatory properties, could explain its tissue repair effects observed in vivo.

Análise e monitoramento da qualidade de produtos farmacêuticos contendo Hypericum perforatum L. comercializados em Divinópolis Minas Gerais Brasil / Analysis and monitoring of the quality of pharmaceutical products containing Hypericum perforatum L. marketed in Divinópolis State of Minas Gerais Brazil

The growing trade market in herbal medicines is aworldwide phenomenon due to several factors, fromthe high cost of manufactured drugs to mere fashion.In this study, we tested the quality of pharmaceuticalproducts based on Hypericum perforatum L. (Eng. ?StJohn?s Wort?) marketed in Divinópolis City, State ofMinas Gerais, Brazil. Samples of products labeled H.perforatum were purchased at three commercial stores,at various times during one year. We assessed thefollowing items: pharmacobotanical characteristics,humidity, total ash, hypericin content and thin layerchromatographic profile. Close inspection showed that4 of the 12 samples sold as H. perforatum products werefrom a different plant from that advertised, representinga forgery in which the true species was replaced byAgeratum sp. Besides, the samples did not entirely meetthe legal requirements for herbal medicine. Therefore,there is a need to strengthen pharmaceutical vigilance,to ensure that herbal products are suitable for publicuse.

O crescente comércio de plantas medicinais e fitoterápicos ocorre em todo o mundo em razão de diversos fatores, como o alto custo dos medicamentos industrializados ou modismo. Neste trabalho verificou-se a qualidade de produtos farmacêuticos contendo Hypericum perforatum L. comercializados em Divinópolis, Minas Gerais, Brasil. Adquiriram-se amostras de H. perforatum em três estabelecimentos distintos em diferentes épocas ao longo de um ano. Avaliaram-se os seguintes itens: aspectos farmacobotânicos, umidade, cinzas totais, doseamento de hipericina e cromatografia em camada delgada. Os resultados demonstraram que quatro amostras comercializadas como H. perforatum eram produtos diferentes daqueles anunciados, caracterizando uma falsificação e substituição da espécie verdadeira por Ageratum sp. Além disso, as amostras não cumpriram totalmente os requisitos exigidos pela legislação. Portanto, faz-se necessário reforçar a vigilância farmacêutica, buscando garantir produtos de qualidade adequados ao uso da população.

Hypericum perforatum L. as Adjuvant to Opioid Analgesia in an Animal Model of Migraine.

Aims: Despite their high analgesic efficacy, opioids can provide only partial pain relief during a migraine attack and their tolerability profile is unsatisfactory. The aim of the present study was to investigate the potentiating properties of Hypericum perforatum L. (SJW) to identify a safe and tolerable adjuvant to opioid analgesia in migraine therapy. Study Design: Experimental study. Place and Duration of Study: Department of Neuroscience, Psychology, Drug Research, and Child Health (NEUROFARBA), University of Florence, Florence, Italy, between September 2008 and July 2009. Methodology: A mouse model of meningeal nociception induced by administration of the nitric oxide donor sodium nitroprusside (SNP) was used. The following treatment groups were used: saline, SNP, morphine, SJW, SNP+morphine, SNP+SJW, SNP+morphine+SJW. The presence of thermal allodynia was evaluated through the cold plate test. The presence of behavioural side effects was determined by the evaluation of locomotor activity (rotarod test), spontaneous mobility and inspection activity (hole board test). Results: SNP induced a long lasting thermal allodynia that appeared after 1 h, peaked after 3-4 h and disappeared 6 h after administration. The co-injection of a single low dose of SJW (1 mg/kg) with morphine (2-5 mg/kg) greatly increased the opioid analgesia (P<.05). SJW, when administered alone,was unable to counteract SNP-induced allodynia. Among the main components of this herbal drug, hypericin produced a potentiating activity comparable to that induced by SJW whereas hyperforin and flavonoids were ineffective. Animal gross’ behavior and locomotor activity were not altered by co-administrationof morphine and SJW. Conclusion: Present results showed the potentiating activity of SJW on morphine antinociception in an animal model of migraine. This herbal drug might be proposedas adjuvant to opioid agonists to produce analgesia using lower, safer doses of opioids. This combination might represent a therapeutic perspective for migraine pain.

Aspectos botânicos, químicos, farmacológicos e terapêuticos do Hypericum perforatum L / Botanical, chemical, pharmacological and therapeutic aspects of Hypericum perforatum L

Estima-se que aproximadamente 25% das drogas prescritas em todo o mundo são oriundas de espécies vegetais. Dentre as plantas com alto potencial medicinal, se destaca o Hypericum perforatum L. (HP), planta herbácea perene, pertencente à família Hypericaceae. Extratos orgânicos e aquosos de HP têm sido utilizados na medicina popular e em testes pré-clínicos para o tratamento e prevenção de diversas doenças através de efeitos nefroprotetores, atividades antioxidante, antifúngica, ansiolítica, antiviral e cicatrizante. Estudos clínicos indicaram que esta espécie pode ser útil no tratamento de desordens originadas do sistema nervoso central, especialmente na depressão unipolar. HP contém, ao menos, dez classes de compostos biologicamente ativos, dentre eles antraquinonas/naftodiantronas, derivados de floroglucinol, flavonoides, biflavonas, xantonas, óleos voláteis, aminoácidos, vitamina C, cumarinas, taninos e carotenoides. Ao mesmo tempo em que os constituintes possuem relevantes efeitos farmacológicos, os mesmos podem prejudicar, por antagonismo farmacocinético (interação com algumas enzimas do citocromo), a eficácia de outros fármacos. Devido a relevante importância do HP como agente terapêutico, ressalta-se a importância do desenvolvimento de novos estudos com o intuito de elucidar questões ainda controversas acerca do extrato de HP, e.g., dose, melhor horário para colheita, padronização dos extratos, e possíveis efeitos tóxicos, podendo assim, definir claramente os riscos e benefícios da utilização desta planta.

It is estimated that approximately 25% of prescribed drugs are derived from plant species. Among the plants with high medicinal potential, it highlights the Hypericum perforatum L. (HP), perennial herbaceous plant belonging to the family Hypericaceae. Organic and aqueous extracts of HP have been used in folk medicine and in pre-clinical testing for the treatment and prevention of several diseases through effects nefroprotetores, antioxidant, antifungal, anxiolytic, wound healing and antiviral activities. Clinical studies indicated that this specie can be useful in the treatment of central nervous system disorders, especially to unipolar depression. HP contains at least ten classes of biologically active compounds, including anthraquinones/naftodiantronas, phloroglucinol derivatives, flavonoids, biflavones, xanthones, volatile oils, amino acids, vitamin C, coumarins, carotenoids and tannins. At the same time that the secondary metabolites have important pharmacological effects, they can impair the effectiveness of other drugs by pharmacokinetic antagonism.

Hypericum Perforatum Decreased Hippocampus TNF-alpha and Corticosterone Levels with No Effect on Kynurenine/Tryptophan Ratio in Bilateral Ovariectomized Rats

The present study was designed to investigate the effect Hypericum Perforatum (HP), on behavioral changes, corticosterone, TNF-alpha levels and tryptophan metabolism and disposition in bilateral ovariectomized rats compared to 17alpha -ethinylestradiol. Behavioral analysis by measuring immobility time in forced swimming test and open field test, serum and hippocampal corticosterone and TNF-alpha along with hippocampal kynurenine/tryptophan ratio were determined in mature ovariectomized rats treated orally either by HP at three different doses 125, 250, and 500 mg/kg/day or by 17alpha-ethinylestradiol 30 microg/kg/day for 30 days. Ovariectomized rats showed significant increase in immobility time in the forced swimming test. Along with elevation in serum and hippocampal TNF-alpha and corticosterone levels associated with significant increase in hippocampal kynurenine/tryptophan ratio. Immobility time in the forced swimming test was decreased in rats treated by different doses of HP in a dose dependent manner and 17alpha-ethinylestradiol with no concomitant changes in the open field test. Only Rats treated with HP exhibited significant decrease in the elevated serum and hippocampal TNF-alpha and corticosterone, which couldn't explain the associated insignificant effect on hippocampaus kynurenine/tryptophan ratio in comparison to ovariectomized untreated rats. It is concluded that increased tryptophan metabolism toward kynurenine secondary to elevated corticosterone and TNF-alpha might be one of the pathohphysiological mechanisms that could explain depression like state observed in this rat model. Further, the observed attenuating effect of HP on TNF-alpha and corticosterone could contribute in its antidepressant effect in this animal model by other ways than their effects on tryptophan-kynurenine metabolism pathway.

Effect of St. John's Wort (Hypericum perforatum) on obesity, lipid metabolism and uterine epithelial proliferation in ovariectomized rats

BACKGROUND/OBJECTIVES: This study was conducted to assess the potential of St. John's Wort (Hypericum perforatum) to prevent obesity and abnormalities in lipid metabolism induced by ovariectomy in a rat model without stimulatory activity on uterus. MATERIALS/METHODS: Ovariectomized (OVX) rats were treated for 6 weeks with 70% ethanol extracts of Hypericum perforatum [HPEs: whole plant (WHPE) and flower and leaves (FLHPE)], beta-estradiol-3-benzoate at a dose of 50 microg/kg/day (E2) or vehicle (distilled water). RESULTS: As expected, OVX increased body weight gain and adiposity and showed higher food efficacy ratio. OVX also increased the serum cholesterol as well as insulin resistance, while reducing uterus weight and uterine epithelial proliferation rate. HPEs (WHPE and FLHPE) showed estrogen-like effect on body weight gain, adipose tissue weight and food efficacy ratio in OVX rats. HPEs prevented hypercholesterolemia induced by OVX more effectively than E2. E2 increased uterus weight and epithelial proliferation rate in OVX rats, while HPEs maintained them at the level of the sham-operated animals. CONCLUSIONS: Our finding demonstrates that HPEs can be considered as an effective agent to prevent OVX-induced obesity without stimulatory activity on uterus.

Evaluation of postpartum behaviour in rats treated with Hypericum perforatum during gestation

Gestational depression is detrimental to the health of the mother and the offspring and contributes to the appearance of depressive and anxiety symptoms during the postnatal period. Traditional antidepressants have undesirable side effects when utilised during gestation, but Hypericum perforatum has been characterised as an efficient and safe antidepressant that prevents the recurrence of symptoms. This study verified the effects of Hypericum perforatum on the behaviour of Wistar rats that were treated during gestation and evaluated 10 and 60 days post-treatment. Pregnant Wistar rats were divided into four groups of ten animals each: one control group that received distilled water and three treatment groups that were treated orally with 36, 72 or 144 mg/kg Hypericum perforatum extract. At 10 and 60 days after parturition and post-treatment, the rats were submitted to the holeboard, the tail suspension, and the forced swim tests. The animals treated with 144 mg/kg Hypericum perforatum exhibited greater head-dipping activity in the hole-board test and reduced immobility in the tail suspension and forced swim tests, suggesting less anxiety and depression 10 and 60 days post-treatment.The results indicated that treating rats with Hypericum perforatum during the gestational period decreased depressive behaviour and anxiety 10 and 60 days post-treatment.

Fluoxetina ou Hypericum perforatum no tratamento de pacientes portadores de transtorno depressivo maior leve a moderado: uma revisão / Fluoxetine or Hypericum perforatum to treat mild to moderated major depressive disorder patients: a review

Conhecidos há mais de 2.500 anos, os transtornos afetivos continuam a dominar os interesses da saúde pública, com destaque ao transtorno depressivo maior (TDM). Diversos antidepressivos foram desenvolvidos destacando-se os Inibidores Seletivos da Recaptura de Serotonina (ISRS), entre eles, a fluoxetina medicamento de primeira escolha no manejo do TDM. Em contrapartida, os extratos do Hypericum perforatum (HP) vêm tomando destaque, representando os antidepressivos mais prescritos em vários países europeus. Essa revisão teve por objetivo analisar a eficácia e a aceitação das formas mais prevalentes de terapias medicamentosas do TDM leve a moderado: fluoxetina e HP, por meio de estudos avaliados, a partir de 2005, identificados nas bases de dados MEDLINE, Ovid, ScienceDirect, além de referências bibliográficas. Dentre os estudos avaliados, três consideraram o HP mais eficaz que fluoxetina, um o considerou menos eficaz e um não demonstrou diferença. Os trabalhos que avaliaram a aceitação foram unânimes quanto à superioridade do HP. Os trabalhos analisados são controversos quanto à eficácia do HP no manejo do TDM. Todos os estudos utilizaram doses de 900 mg de HP administrados uma a três vezes ao dia, contra 20 mg de fluoxetina uma vez ao dia. O tempo de tratamento realizado variou de 4 a 12 semanas, analisando o tratamento em depressão leve a moderada e apenas um estudo avaliou depressão com parâmetros vegetativos invertidos. Há, portanto, necessidade de mais estudos com tratamento em longo prazo, variando as doses das medicações a fim de avaliar se o HP consiste em mais uma arma contra o TDM leve a moderado.

Know over 2.500 years, affective disorders still present major interest in the public health studies, particularly the major depressive disorder (MDD). Several antidepressant drugs have been developed, including the selective serotonin reuptake inhibitors (SSRI) fluoxetine, the first choice for the MDD drug-therapy. Besides that, Hypericum perforatum (HP) extracts have been more and more prescribed, and are the most used antidepressants in several European countries. This review had, as its objective, to evaluate efficiency and compliance to the treatment of mild to moderated MDD patients: fluoxetine and HP extracts, through studies published from 2005, identified in MEDLINE, Ovid, ScienceDirect databases as well as textbooks. Among these studies, three papers considered HP as more efficient than fluoxetine, one paper had the opposite conclusion and one did not demonstrate any significant difference. The studies that evaluated the tolerance were unanimous about the superiority of HP. HP efficiency in MDD treatment was controversial. All papers revised used one to three doses of HP 900 mg/day and a single fluoxetine 20 mg/day dose. The treatment was carried out for 4-12 weeks, and the patients were diagnosed with mild to moderated MDD. Further studies, including other dosage regimens and long-term treatments, must be carried out in order to provide consistent data on mild or moderated MDD drug-therapy for health professionals involved with the treatment of patients in this clinical condition.

Long-term maintenance of in vitro cultures affects growth and secondary metabolism of St. John's Wort / A manutenção prolongada de culturas in vitro afeta o crescimento e o metabolismo secundário de hipérico

Hypericum perforatum is a traditional medicinal plant with wound healing and antidepressant properties. Efficiency of micropropagation is often related to the long term maintenance of tissues in culture, which may alter the secondary metabolism of plants. The objective of this study was to evaluate growth and secondary metabolism of in vitro shoots of H. perforatum on short and long term maintenance of cultures (30 and 100 days). The effect of BA and NAA supplementation was evaluated during 30 days of culture. Adventitious shoots were cultivated on MS medium supplemented with 4.4mM BA alone or in combination with 0.05mM NAA for 30 days. A hormone-free medium was used as control. Shoots cultivated for 100 days were maintained in presence of 4.4mM BA. Biomass, multiplication of shoots, contents of phenolic compounds, flavonoids and hypericin were evaluated. No difference between BA and BA+NAA was observed on growth, multiplication of shoots and levels of flavonoids at the end of 30 days of culture. Production of phenolic compounds was promoted by addition of BA+NAA to the medium, whereas hypericin was increased by the presence of BA. The time of culture (30 and 100 days) affected all the parameters analyzed, except the levels of flavonoids in the short term experiment.

Hypericum perforatum é uma planta medicinal que apresenta propriedades cicatrizante e antidepressiva. Frequentemente, a eficiência da micropropagação está relacionada à manutenção dos tecidos em cultura por longos períodos, o que pode alterar o metabolismo secundário das plantas. O objetivo deste trabalho foi avaliar o crescimento e o metabolismo secundário de brotações adventícias de H. perforatum mantidas por diferentes tempos de cultivo (30 e 100 dias). O efeito da adição de BA e ANA foi avaliado no período de 30 dias. As brotações foram cultivadas em meio MS suplementado com 4,4mM BA como único regulador ou em combinação com 0,05mM ANA, por 30 dias. Um meio de cultivo sem adição de reguladores foi utilizado como controle. As brotações cultivadas por 100 dias foram mantidas em presença de 4,4mM BA. A biomassa, a multiplicação dos brotos, as concentrações de compostos fenólicos, flavonoides e hipericina foram os parâmetros avaliados. Nenhuma diferença entre a adição de BA ou BA+ANA foi observada quanto ao crescimento, ao número de brotos e aos níveis de flavonoides ao final de 30 dias de cultivo. Diferenças neste período foram detectadas nos níveis de compostos fenólicos e de hipericina quando os brotos foram cultivados em presença de BA+NAA e de BA, respectivamente. O tempo de cultivo (30 e 100 dias) afetou todos os parâmetros avaliados, com exceção dos níveis de flavonoides no período de 30 dias.

In vitro Anti-Hepatitis B Virus Effect of Hypericum perforatum L / 华中科技大学学报（医学）（英德文版）

The anti-hepatitis B virus(HBV)effects and its mechanisms of the ethanol extracts of Hypericum perforatum L.(EHP)in vitro were explored.HepG2 2.2.15 cells,a stable HBV-producing cell line,were cultured as the model system to observe the anti-HBV effect.The viral antigens of cellular secretion,HBsAg and HBeAg,were determined by enzyme linked immunosorbent assay(ELISA).The quantity of HBV-DNA released in the supernatant was assayed by real-time PCR.In order to understand the mechanisms of the suppression of HBV replication,all HBV promoters(Cp,Xp,S1p,S2p and Fp)with luciferase reporter gene were transfected into HepG2 cells respectively.Then the activities of viral promoters were examined by luciferase reporter assay.It was found EHP effectively suppressed the secretion of HBsAg and HBeAg from HepG2 2.2.15 cells in a dose-dependent manner,as well as the extracellular HBV DNA.And EHP could selectively inhibit the activity of HBV promoter Fp.Our data suggest that EHP exerts anti-HBV effects via inhibition of HBV transcription,which helps to elucidate the mechanism underlying the potential therapeutic value of EHP.