Hypericum Extract Research Articles

Antiradiation properties of extracts from Hypericum perforatum L.

Aim. Considering the high biological activity of the components of the St. John’s wort, we conducted studies to identify its radioprotective effect. Methods. Studies were conducted on adult Vistar rats with an average weight of 100-120 grams.3 hours before irradiation, the extract from St. John’s wort was intraperitoneally administered to animals at a concentration of 50 mg/kg. Irradiation was carried out once with doses of 5 and 7 Gy on the “Rhund-20000” facility with an average radiation dose rate MD = 0.3069 Gr/s. The frequency of chromosomal abnormalities was recorded on the mitotic cells of the bone marrow. Results. Acute irradiation with a dose of 5 Gy led to cell division inhibition. The number of chromosomal aberrations increased due to structural disorders (deletions, fragments, inversions) up to 6.8%.In animals that received a dose of 7 Gy after a single irradiation, the frequency of chromosomal abnormalities increased to 11.02%. The introduction of the Hypericum perforatum L. extract softened the effect of ionizing radiation, reducing the mutational effect of radiation. It not only contributed to the restoration of the cell division, but also reduced the proportion of structural disorders. Conclusions. Hypericum extract can be considered to be promising as an anti-radiation agent of plant origin.
 Keywords: rats, chromosomal abnormalities, marrow, irradiation, extract.

Antioxidant and Cytotoxic Activities of Aerial and Underground Parts of Hypericum Scabrum L.

We have studied Hypericum scabrum L. plant which belongs to the Hypericaceae family, naturally growing in Anatolia. The aim of this research is to investigate the chemical composition (total phenol, total flavonoid) of 70% methanol and water extracts prepared from the underground and flowering aerial parts to investigate the antioxidant and cytotoxic activity. In order to determine the antioxidant activities of the extracts, 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities and the inhibition of β-carotene/linoleic acid co-oxidation were studied. In cytotoxicity experiments, 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium (MTT) method was used on human lung cancer cell line (A549), human colon adenocarcinoma cell line (COLO 205) and mouse fibroblast (L929) cell line. When the chemical composition of the extracts was examined, the richest extract in terms of total phenolic content was found to be water extract prepared form the flowering part of the plant, and this extract was evaluated to be more active in DPPH radical scavenging activity test than the other extracts. In the cytotoxicity assays, 70% methanol extracts prepared from the flowering and root parts of the plant showed more inhibitory effects on cell viability than water extracts. Our experimental evidence suggests that these Hypericum extracts may be useful as antioxidant and cytotoxic agents.

Discovery of key regulators of dark gland development and hypericin biosynthesis in St. John's Wort (Hypericum perforatum).

SummaryHypericin is a molecule of high pharmaceutical importance that is synthesized and stored in dark glands (DGs) of St. John's Wort (Hypericum perforatum). Understanding which genes are involved in dark gland development and hypericin biosynthesis is important for the development of new Hypericum extracts that are highly demanded for medical applications. We identified two transcription factors whose expression is strictly synchronized with the differentiation of DGs. We correlated the content of hypericin, pseudohypericin, endocrocin, skyrin glycosides and several flavonoids with gene expression and DG development to obtain a revised model for hypericin biosynthesis. Here, we report for the first time genotypes which are polymorphic for the presence/total absence (G+/G−) of DGs in their placental tissues (PTs). DG development was characterized in PTs using several microscopy techniques. Fourier transform infrared microscopy was established as a novel method to precisely locate polyaromatic compounds, such as hypericin, in plant tissues. In addition, we obtained transcriptome and metabolome profiles of unprecedented resolution in Hypericum. This study addresses for the first time the development of dark glands and identifies genes that constitute strong building blocks for the further elucidation of hypericin synthesis, its manipulation in plants, its engineering in microbial systems and its applications in medical research.

Rutin as Deoxyribonuclease I Inhibitor.

DNase I inhibitory potential of water extract of nine Hypericum species (H. umbellatum, H. barbatum, H. rumeliacum, H. rochelii, H. perforatum, H. tetrapterum, H. olympicum, H. hirsutum, H. linarioides) and the most important Hypericum secondary metabolites (hypericin, hyperforin, quercetin, and rutin) was investigated. All examined Hypericum extracts inhibited DNase I with IC50 below 800 μg/ml, whereby H. perforatum was the most potent (IC50 =391.26±68.40 μg/ml). Among the investigated Hypericum secondary metabolites, rutin inhibited bovine pancreatic DNase I in a non-competitive manner with IC50 value of 108.90±9.73 μm. DNase I inhibitory ability of rutin was further confirmed on DNase I in rat liver homogenate (IC50 =137.17±16.65 μm). Due to the involvement of DNase I in apoptotic processes the results of this study indicate the importance of frequent rutin and H. perforatum consumption in daily human nutrition. Rutin is a dietary component that can contribute to male infertility prevention by showing dual mechanism of sperm DNA protection, DNase I inhibition and antioxidant activity.

Сорбционные характеристики сорбентов для твердофазной экстракции фенольных соединений из экстрактов лекарственных растений

В основе исследований настоящей работы находится твердофазное извлечение фенольных компонентов экстрактов лекарственного растительного сырья различными типами сорбционных материалов. В качестве сорбционных материалов использовали октадецилсиликагель (Strata C18-E), сополимер стирола и дивинилбензола, химически модифицированный N-винилпирролидоном,(Strata X), а также сополимер дивинилбензола и N-винилпирролидона (Oasis HLB). Для каждого из сорбентов получены сорбционные характеристики по отношению к целевым соединениям (объем до проскока, равновесный объем, объем удерживания и др.), а также десорбционные параметры (коэффициент концентрирования и степень извлечения). Показано, что сорбенты на основе октадецилсили-кагеля достаточно эффективны для извлечения группы флавоноидов и их гликозидов, а полимерные материалы - одновременно и флавоноидов, и фенольных кислот. Степени извлечения фенольных кислот и флавоноидов при коэффициенте концентрирования 5 на сорбенте Strata C18-E составили 27-40% и 79-105% соответственно. С применением сорбента Strata X также достигается концентрирова-ние в 5 раз при степенях извлечения 106-107% (для фенольных кислот) и 99-122% (для флавоноидов). На сорбенте Oasis HLB возможно концентрирование в 20 раз фенольных кислот при их степенях извлечения 74-96% и в 32 раза для флавоноидов при степенях извлечения в диапазоне 56-91%.

Distinct Hypericum perforatum L. total extracts exert different antitumour activity on erythroleukemic K562 cells.

Total flower extracts of Hypericum perforatum L. obtained with 3 different solvent systems were tested on tumour cell line cultures by comparing two groups of plants harvested in different times and places. The extracts, characterized according to the spectroscopic profile and the hypericin content, were tested on the growth and apoptotic death of K562 cells, a human erythroleukemic cell line. Growth and apoptosis were analysed by viable cell count, flow cytometry, and fluorescence microscopy at 6, 24, and 48hr of culture following 1 hr exposure to the extracts under investigation. Here, we show that Hypericum extracts are able to reduce the growth of K562 cells and induce different degrees and kinetics of apoptosis according to the group of plants of origin. Also, we highlighted interesting differences in terms of efficacy among the extracts, with some samples losing their effectiveness along the culture time and others able to maintain or even increase their efficacy. Furthermore, the data herein obtained confirm the role of non hypericin compounds that are present in different proportions in the two plant groups and in the extracts analysed.

Extracts From Hypericum hircinum subsp. majus Exert Antifungal Activity Against a Panel of Sensitive and Drug-Resistant Clinical Strains.

During the last two decades incidences of fungal infections dramatically increased and the often accompanying failure of available antifungal therapies represents a substantial clinical problem. The urgent need for novel antimycotics called particular attention to the study of natural products. The genus Hypericum includes many species that are used in the traditional medicine to treat pathological states like inflammations and infections caused by fungi. However, despite the diffused use of Hypericum-based products the antifungal potential of the genus is still poorly investigated. In this study five Hypericum species autochthonous of Central and Eastern Europe were evaluated regarding their polyphenolic content, their toxicological safety and their antifungal potential against a broad panel of clinical fungal isolates. LC-MS analysis led to the identification and quantification of 52 compounds, revealing that Hypericum extracts are rich sources of flavonols, benzoates and cinnamates, and of flavan-3-ols. An in-depth screen of the biological activity of crude extracts clearly unveiled H. hircinum subsp. majus as a promising candidate species for the search of novel antifungals. H. hircinum is diffused in the Mediterranean basin from Spain to Turkey where it is traditionally used to prepare a herbal tea indicated for the treatment of respiratory tract disorders, several of which are caused by fungi. Noteworthy, the infusion of H. hircinum subsp. majus excreted broad antifungal activity against Penicillium, Aspergillus and non-albicans Candida isolates comprising strains both sensitive and resistant to fluconazole. Additionally, it showed no cytotoxicity on human cells and the chemical characterization of the H. hircinum subsp. majus infusion revealed high amounts of the metabolite hyperoside. These results scientifically support the traditional use of H. hircinum extracts for the treatment of respiratory tract infections and suggest the presence of exploitable antifungal principles for further investigations aimed at developing novel antifungal therapies.

Efficacy of a hypericum extract (STW3-VI) – A reanalysis

IntroductionThe course of depression during therapy in studies is usually monitored by scales like HAMD. Also the course of single items of the HAMD during therapy might be of specific interest as some symptoms are of highly predictive value. Furthermore early improvement during antidepressive therapy is a new aspect which came into the focus.ObjectivesThe objectives of this study were to reanalyze clinical data regarding early improvement as well as specific symptoms or symptom cluster – like sleep disturbances.AimsThe aim of this study was to get deeper insight into the data structure of 2 RCTs (n = 398, 42 days treatment) comparing the efficacy of a hypericum extract (STW3-VI/900 mg once daily) to Placebo.MethodsData structure was evaluated by comparing the total scores of the HAMD-17 to a single item analysis and by calculating the factorial structure of the end of treatment data. The treatment potential was evaluated by calculating a positive predictive value from day 7 to the end of treatment. ANCOVA, factor analysis and regression methods were used.ResultsThe single item analyses were widely comparable to the highly significant treatment differences of the total scores as it were the calculated subscales. The positive predictive value of the treatment was about 75%.ConclusionsThe results underline the elsewhere proven treatment efficacy of STW3-VI regarding several new subscale aspects.Disclosure of interestCOI: The authors are employees of Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany.

Efficacy of hypericum extract Ws® 5570 compared with paroxetine in patients with a moderate major depressive episode–a subgroup analysis

IntroductionVarious studies showed the efficacy and tolerability of WS® 5570 (Hyperiplant® Rx, Dr. Willmar Schwabe GmbH & Co. KG) 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.Objectives/aimsWe 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. This analysis on moderately depressed patients treated with WS® 5570 tries to support the hypothesis that WS® 5570 is an effective remedy in patients with major depression and moderate symptom intensity.MethodsModerate depression was defined by a baseline Hamilton Depression Rating Scale (HAM-D) total score between 22 and 25. Sixty-four patients received, after a single blind placebo run-in phase of 3–7 days, either 3 × 300 mg/day WS® 5570 or 20 mg/day 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.ResultsThe reduction of the HAM-D total score was significantly more pronounced in patients treated with 3 × 300 mg/day WS® 5570 compared to 20 mg/day paroxetine. After six weeks, responder (87.1%) and remission rates (60.6%) to WS® 5570 were significantly higher than to paroxetine (71%/42.4%).ConclusionsAfter six weeks, patients treated with WS® 5570 showed a higher reduction in depression severity score and yielded greater response and remission rates compared with patients treated with paroxetine.Disclosure of interestSupported by Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany

Rats treated with Hypericum perforatum during pregnancy generate offspring with behavioral changes in adulthood

Drugs used in the treatment of depression can cross the placenta giving rise to questions regarding the effects these drugs exert on the fetus. Hypericum perforatum L., Hypericaceae, is a natural product used to treat depression. However, information about its toxicity and the occurrence of alterations in the central nervous system development of the offspring is scarce. This work assessed the behavior of adult male rats born from mothers treated with Hypericum extract during gestation and analyzed the fluorescence of the extract in different organs of mothers and fetuses. Male pups were divided into three treated groups, corresponding to the administration of the Hypericum extract to mothers at the dose levels of 36mg/kg, 72mg/kg and 144mg/kg, and one control group in which the mothers received distilled water. At 90 days of age, the offspring underwent the following tests: rotarod, pentobarbital-induced sleep time, elevated plus maze, hole-board and forced swimming test. The observed fluorescence indicated the presence of the extract in all tissues analyzed. The obtained results suggest lasting changes in the performances displayed in the CNS, depression and anxiety tests, indicating that the use of Hypericum during gestation could interfere with the behavioral development of the offspring reducing anxiety and depression when they become adults. We suggest that these alterations are associated with the reprogramming of the brain regions related to changes in emotional reactivity.

A systematic review of St. John's wort for major depressive disorder.

BackgroundThis systematic review evaluated St. John’s wort (SJW) for the treatment of Major Depressive Disorder (MDD). The objectives of this review are to (1) evaluate the efficacy and safety of SJW in adults with MDD compared to placebo and active comparator and (2) evaluate whether the effects vary by severity of MDD.MethodsWe searched PubMed, CINAHL, PsycINFO, CENTRAL, Embase, AMED, MANTIS, Web of Science, and ICTRP and existing reviews to November 2014. Two independent reviewers screened the citations, abstracted the data, and assessed the risk of bias. We included randomized controlled trials (RCTs) examining the effect of at least a 4-week administration of SJW on depression outcomes against placebo or active comparator in adults with MDD. Risk of bias was assessed using the Cochrane Risk of Bias tool and USPSTF criteria. Quality of evidence (QoE) was assessed using the GRADE approach.ResultsThirty-five studies examining 6993 patients met inclusion criteria; eight studies evaluated a hypericum extract that combined 0.3 % hypericin and 1–4 % hyperforin. The herb SJW was associated with more treatment responders than placebo (relative risk [RR] 1.53; 95 % confidence interval [CI] 1.19, 1.97; I2 79 %; 18 RCTs; N = 2922, moderate QoE; standardized mean differences [SMD] 0.49; CI 0.23, 0.74; 16 RCTs; I2 89 %, N = 2888, moderate QoE). Compared to antidepressants, SJW participants were less likely to experience adverse events (OR 0.67; CI 0.56, 0.81; 11 RCTs; moderate QoE) with no difference in treatment effectiveness (RR 1.01; CI 0.90, 1.14; 17 RCTs, I2 52 %, moderate QoE; SMD −0.03; CI −0.21, 0.15; 14 RCTs; I2 74 %; N = 2248, moderate QoE) in mild and moderate depression.ConclusionsSJW monotherapy for mild and moderate depression is superior to placebo in improving depression symptoms and not significantly different from antidepressant medication. However, evidence of heterogeneity and a lack of research on severe depression reduce the quality of the evidence. Adverse events reported in RCTs were comparable to placebo and fewer compared with antidepressants. However, assessments were limited due to poor reporting of adverse events and studies were not designed to assess rare events. Consequently, the findings should be interpreted with caution.Systematic review registrationPROSPERO CRD42015016406.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0325-2) contains supplementary material, which is available to authorized users.

Evaluation of the cytotoxic activity of Hypericum spp. on human glioblastoma A1235 and breast cancer MDA MB-231 cells

ABSTRACTCytotoxic activity of 16 Hypericum ethanolic extracts was evaluated by MTT assay on two human cancer cell lines: glioblastoma A1235 and breast cancer MDA MB-231. Morphology and the type of induced cell death were determined using light and fluorescence microscopy. The majority of Hypericum extracts had no significant cytotoxic effect on MDA MB-231 cells. Eight extracts exhibited mild cytotoxic effect on A1235 cells after 24 h incubation, ranging from 8.0% (H. patulum) to 21.7% (H. oblongifolium). After 72 h of treatment, the strongest inhibition of A1235 viability was observed for extracts of H. androsaemum (26.4–43.9%), H. balearicum (25.8–36.3%), H. delphicum (14.8–27.4%) and H. densiflorum (11.2–24.1%). Micro-scopic examination of cells showed apoptosis as the dominant type of cell death. Due to observed high viability of treated cells, we propose that cytotoxic effects of Hypericum extracts could be related to alternations/interruptions in the cell cycle.

Efficacy of Hypericum extract WS® 5570 compared with paroxetine in patients with a moderate major depressive episode – a subgroup analysis

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.

New Potential Pharmaceutical Applications of Hypericum Species.

The genus Hypericum includes more than 450 species distributed in Europe, North America, North Africa and West Asia. These plants are widely used in folk medicine for the treatment of inflammation, bacterial and viral infections, burns and gastric disorders. The use for alleviating inflammation and promoting wound healing is well known for H. Perforatum L. (St. John's wort) and other species. Because of its pharmacological activity, H. perforatum L. is one of the most important species of this genus. This plant has been largely utilized for its efficacy in the treatment of mild to moderate depression. However, some other species have been utilized in traditional medicine and have been studied for their phytochemical composition and for their biological activities to date. Hypericum species contain biologically active secondary metabolites belonging to at least ten different classes, with prevalence of naphthodianthrones (hypericin and pseudohypericin), phloroglucinols (hyperforin), flavonoids (rutin, hyperoside, isoquercitrin, quercitrin, quercetin, amentoflavone) and phenylpropanoids (chlorogenic acid). However, great variations in contents have been reported for wild populations worldwide. The purpose of this review is to provide an overview of most recent studies about potential pharmaceutical applications of plants belonging to Hypericum genus. The most interesting isolated active principles and both in vitro and in vivo effects of Hypericum extracts are presented and discussed.

PROTECTIVE EFFECTS OF HYDROALCOHOLIC EXTRACT OF HYPERICUM PERFORATUM AGAINST BLEOMYCIN-INDUCED PULMONARY FIBROSIS IN RATS

BACKGROUND AND OBJECTIVE: Pulmonary fibrosis is a chronic interstitial lung disease caused by parenchymal lung damage due to inflammatory factors and fibrosis. Hypericum perforatum contains various flavonoids with antioxidant properties. This study aimed to evaluate protective effects of hydroalcoholic extract of Hypericum against bleomycin-induced pulmonary fibrosis in rats. METHODS: This empirical study was conducted on 30 Wistar rats weighing 150-180 grams. Animals were randomly divided into five groups of six. Group one received a single dose of normal saline intraperitoneally, and group two was administered with bleomycin (7.5 units per kg) intratracheally. Other groups received daily doses of Hypericum extract (50, 100 and 200 mg/kg) via intraperitoneal injection one week before and two weeks after bleomycin administration. After 21 days, animals were sacrificed, and blood and lungs were collected for histopathological examinations, and measurement of plasma malondialdehyde (MDA) and lung hydroxyproline (HP). FINDINGS: In this study, lung index, HP and plasma MDA in normal saline group were respectively 7.09±0.32 mg per kilogram of body weight, 1.80±0.23 mg per gram of lung tissue, and 1.32±0.27 micromoles per liter of plasma. In rats administered with bleomycin, these values were 9.75±0.90, 5.43±0.7 and 3.04±0.42, respectively. Treatment with Hypericum extract, especially at dosage of 200 mg/kg, resulted in a significant reduction in the aforementioned parameters compared to bleomycin group (p<0.05). CONCLUSION: According to the results of this study, hydroalcoholic extract of Hypericum perforatum could exert protective effects against bleomycin-induced pulmonary fibrosis.

Pharmacological basis for the use of Hypericum oblongifolium as a medicinal plant in the management of pain, inflammation and pyrexia

BackgroundThe present therapeutic agents for the treatment of pain, inflammation and pyrexia are not very effective and accompanied by various side effects. Therefore, new effective agents are the most wanted. The present study investigates the anti-nociceptive, anti-inflammatory and antipyretic activities of crude methanol extract of Hypericum oblongifolium.MethodsIn vivo acetic acid induced writhing and hot plate tests were used for antinociceptive effects at 100, 200 and 300 mg/kg i.p. The anti-inflammatory and antipyretic potential of methanol extract were tested in carrageenan induced paw edema in mice and yeast induced hyperthermia respectively.ResultsThe extract doses of 100, 200 and 300 mg/kg i.p. revealed significant inhibitory effect (P < 0.001) in acetic acid induced writhing test. Pretreatment of extract at doses of 100, 200 and 300 mg/kg i.p. produced significant anti-inflammatory effect (P < 0.001) in the carrageenan induced paw edema. The methanol extract also showed significant antipyretic effect in yeast induced hyperthermia in mice during various assessment times.ConclusionsThe methanol extract of H. oblongifolium showed significant anti-nociceptive, anti-inflammatory and antipyretic effects in various animal models and thus validates the traditional uses of the plant in said conditions.

Free radical scavenging activity and lipid peroxidation inhibition of Hypericum helianthemoides (spach) Boiss

Antioxidants are compounds that obstruct the oxidation of macromolecules in the body. In general, there are two categories of antioxidants, natural and synthetic. Recently, interest has been increased considerably for obtaining new natural antioxidants. In this study, the scavenging of free radicals such as DPPH, NO and OH by Hypericum helianthemoides extract was evaluated. Also, the antioxidant properties of this extract were evaluated by FRAP, FTC methods and determination phenolic compounds. The plant was collected from north of Fars Province and plant extraction was obtained using ethanol. In DPPH radical scavenging, different concentrations of the Hypericum extract were added to DPPH radical. In hydroxyl radical scavenging, Fenton reaction mixture, TCA and TBA were mixed with Hypericum extract. In nitric radical scavenging, nitropruside was mixed with Hypericum extract and then sulphanilic acid, naphthylene diamine were added. In determination of phenolic compounds, Folin-ciocalteu and sodium carbonate were added to Hypericum extract. In DPPH radical scavenging, the IC50 of Hypericum extract (309.35±6.5µg/ml) was higher than the antioxidant standards, BHT (IC50=81.9±2.6 µg/ml) and quercetin (IC50=60.04±6.48 µg/ml). The highest scavenging of hydroxyl radicals was observed in Hypericum extract (70.3±0.8%, 125 µg/ml). In gallic acid it was (73.8±3.3%). In 200 µg/ml of Hypericum extract scavenged NO radical (85.2±2.7%). In FRAP method, the IC50 of this extract was 109.7±10.5 µg/ml. In FTC method, the inhibition of lipid peroxidation by Hypericum extract, BHT and ascorbic acid were 59.2±2.2, 66.9±0.15, 64.06±0.02 respectively. Total phenol of the plant extract was 3±0.4 mg/g.//

Phytopharmaceutical treatment of anxiety, depression, and dementia in the elderly: evidence from randomized, controlled clinical trials.

Based on subgroup analyses of randomized, controlled clinical trials, we review the efficacy of three phytopharmaceutical drugs, respectively of the corresponding active substances silexan® (WS® 1265, lavender oil) in anxiety disorders, WS® 5570 (Hypericum extract) in major depression, and EGb 761® (Ginkgo biloba extract) in Alzheimer, vascular, or mixed type dementia, in elderly patients aged ≥ 60 years. Four trials were eligible in each indication. Meta-analyses and analyses based on pooled raw data showed that the three drugs were significantly superior to placebo in the elderly subset, and that their treatment effects reflected in the main outcome measures (Hamilton Anxiety scale, Hamilton Depression scale, Neuropsychiatric Inventory) were comparable with those observed in the original trials without age restrictions. The results confirm the efficacy of the three herbal active substances in elderly patients of ≥ 60 years of age. In anxiety, depression, and dementia, they thus represent efficacious and well-tolerated alternatives to synthetic drugs.

Efficacy and acceptability of pharmacological treatments for depressive disorders in primary care: systematic review and network meta-analysis.

The purpose of this study was to investigate whether antidepressants are more effective than placebo in the primary care setting, and whether there are differences between substance classes regarding efficacy and acceptability. We conducted literature searches in MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PsycINFO up to December 2013. Randomized trials in depressed adults treated by primary care physicians were included in the review. We performed both conventional pairwise meta-analysis and network meta-analysis combining direct and indirect evidence. Main outcome measures were response and study discontinuation due to adverse effects. A total of 66 studies with 15,161 patients met the inclusion criteria. In network meta-analysis, tricyclic and tetracyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), a serotonin-noradrenaline reuptake inhibitor (SNRI; venlafaxine), a low-dose serotonin antagonist and reuptake inhibitor (SARI; trazodone) and hypericum extracts were found to be significantly superior to placebo, with estimated odds ratios between 1.69 and 2.03. There were no statistically significant differences between these drug classes. Reversible inhibitors of monoaminoxidase A (rMAO-As) and hypericum extracts were associated with significantly fewer dropouts because of adverse effects compared with TCAs, SSRIs, the SNRI, a noradrenaline reuptake inhibitor (NRI), and noradrenergic and specific serotonergic antidepressant agents (NaSSAs). Compared with other drugs, TCAs and SSRIs have the most solid evidence base for being effective in the primary care setting, but the effect size compared with placebo is relatively small. Further agents (hypericum, rMAO-As, SNRI, NRI, NaSSAs, SARI) showed some positive results, but limitations of the currently available evidence makes a clear recommendation on their place in clinical practice difficult.

Abstract 5117: Cytotoxic effects of hypericum extracts on breast and colorectal tumors

Abstract The risk of acquiring certain types of cancers has many causes which include age, environment and genetics. There have been advances in the primary treatment options available, which include surgery, radiation therapy, and chemotherapy. However, the survival prognosis for many cancer patients remains low. Cancer treatments may involve chemotherapy, which often cause harsh side effects. The Plant kingdom may provide alternative therapy that may have less side effects and possibly more effective. Hypericum perforatum possesses hypericin, which has been been shown to have antitumor effects with invitro studies on specific cell lines. In other Hypericum species, hypericin makes up a smaller percentage of the extract. However, these species contain other phytochemical compounds that may also exert an antitumor effect. The objective of the present study was to assess the cytotoxic potential of H. perforatum cv. topas, H. olympicum, and H. calycinum on breast and colorectal adenocarcinoma cell lines. MCF7, SW480, and SW620 cells were treated with varying concentrations dosages of methanolic crude extracts from the plant species. Cytotoxicity was determine by measuring the reduction of Alamar Blue after a 24 hour exposure period of 10,000 cells in 96 well fluorescent plates. The reduction was determine using the Molecular Devices fluorescent spectrophotometer. At the lowest comparable concentrations, H. perforatum cv. topas had a greater reduction in tumor growth than MCF7 and SW40 cells lines. Whereas, H. olympicum demonstrated a greater decrease in SW620 cell growth at the lowest comparable concentration. These results suggest a difference in the phytochemical composition of these plants, which should be evaluated in order to determine what metabolite(s) are having the antitumor effect and their target. Citation Format: Carla Gibbs, Johnette S. Duggans, Erin Malone, Elbert L. Myles. Cytotoxic effects of hypericum extracts on breast and colorectal tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5117. doi:10.1158/1538-7445.AM2014-5117