Hypericum Androsaemum Research Articles

(±)-Hypandrone A, a pair of polycyclic polyprenylated acylphloroglucinol enantiomers with a caged 7/6/5/6/6 pentacyclic skeleton from Hypericum androsaemum

(±)-Hypandrone A (1), a pair of highly modified PPAP enantiomers, with an unprecedented caged 2,8,17-trioxapentacyclo-[11.4.2.01,9.04,9.010,15]-nonadecane core, were isolated from the fruits of Hypericum androsaemum.

How Changes in Nitrogen Levels Impact Metabolites and Physiological Features of Hypericum androsaemum

Background: The manipulation of mineral nutrition may affect secondary metabolite production and thus determine the nutritional value of food/medicinal plants. Objectives: The present study investigated the impact of nitrogen supply on the production of secondary metabolites and physiological parameters of Hypericum androsaemum plants grown in sand culture. Methods: Four-week plants were irrigated by full-strength Hoagland solution (control), nitrate was reduced to 1/3, and no nitrate was provided for 14 days. Results: The growth of shoots was inhibited by nitrate limitation, but root growth was stimulated. Soluble proteins and water content were significantly affected by nitrate deficiency. Antioxidative enzyme activities (ascorbate peroxidase (APX) and superoxide dismutase (SOD)) were increased due to nitrate deficiency. Treatment of plants with NO3- deficiency caused an increase in total soluble phenols and phenylalanine ammonia-lyase (PAL) activity, while flavonoid content was mainly elevated by NO3- deficiency. At the level of specific metabolites, NO3- deficiency positively affected hypericin and pseudohypericin content but decreased hyperforin content. The expression of the putative gene for hypericin biosynthesis (hyp-1) was up-regulated in response to nitrate deficiency. Conclusions: The results demonstrated that the nitrogen deficiency in the H. androsaemum plant positively affected the antioxidant system, valuable phenols, and secondary metabolites.

Active compounds and biological activities of Hypericum androsaemum L.: A review

Active compounds and biological activities of Hypericum androsaemum L.: A review

Ontogenetic changes in phenolic contents and volatile composition of Hypericum androsaemum and Hypericumxylosteifolium

We described the ontogenetic changes in phenolic contents and volatile composition of Hypericum androsaemum L. and Hypericum xylosteifolium (Spach) N. Robson from Turkish flora for the first time. 30 randomly selected plants were gathered in each of six phenological stages for H. androsaemum (vegetative, floral budding, full flowering, green capsule, red capsule and black capsule) and each of seven phenological stages for H. xylosteifolium (vegetative, floral budding, %10 flowering, %50 flowering, full flowering, green capsule and brown capsule). After dried at room temperature, the plant materials were assayed for phenolic and volatile ingredients by detailed chemical analyses. The accumulations of several phenolics followed a consistent manner but, hyperforin, quercetin, rutin, 2,4 dihydroxybenzoic acid, quercitrin, hyperoside, biapigenin, (+)-catechin and (−)-epicatechin were accumulated at higher levels during floral development depending on species. Germacrene B (31.50%), α-zingiberene (22.75%), α-curcumene (15.21%) β-caryophyllene (14.34%) and naphtalene (11.87%) in H. androsaemum and daucol (23.36%), naphtalene (14.17%) and aromadendrene (10.36%) in H. xylosteifolium were recorded as major volatile components depending on phenophases. Floral budding and flowering phases were characterized by higher accumulation levels of majority of phenolic and volatile compounds in both species indicating these phases as the appropriate harvesting times. These findings can guide the suppliers of Hyperici herba to obtain the raw material that have the highest content of desirable compounds and the most suited chemical composition to the demands of relevant industries. As a remarkable conclusion of this work, H. androsaemum and, especially, H. xylosteifolium can be introduced as new sources of bioactive secondary metabolites.

Ontogenetic Changes in Phenolic Contents and Essential Oil Composition of Hypericum Androsaemum and Hypericum Xylosteifolium

Ontogenetic Changes in Phenolic Contents and Essential Oil Composition of Hypericum Androsaemum and Hypericum Xylosteifolium

Cytotoxic and apoptotic effects of Hypericum androsaemum on prostate adenocarcinoma (PC-3) and hepatocellular carcinoma (Hep G2) cell lines with identification of secondary metabolites by LC-HRMS.

The study aims to determine the secondary metabolites of Hypericum androsaemum L. extracts by liquid chromatography-high resolution mass spectrometry (LC-HRMS), and investigate the antioxidant and cytotoxic activities of the plant. Cytotoxic activity was evaluated by MTT assay, and apoptosis induction abilities on human prostate adenocarcinoma (PC-3), and hepatocellular carcinoma (Hep G2) cell lines. Accordingly, major secondary metabolites were found as hederagenin (762 ± 70.10 μg/g) in the leaves dichloromethane (LD), herniarin (167 ± 1.50 μg/g) in fruit dichloromethane (FD), (-)-epicatechin (6538 ± 235.36 μg/g) in the leaves methanol (LM), (-)-epigallocatechin gallate (758 ± 20.46 μg/g) in the fruit methanol (FM), and caffeic acid (370 ± 8.88 μg/g) in the fruit water (FW), and (3313 ± 79.51 μg/g) in the leaves water (LW) extracts. LM exerted strong antioxidant activity in DPPH free (IC50 10.94 ± 0.08 μg/mL), and ABTS cation radicals scavenging (IC50 9.09 ± 0.05 μg/mL) activities. FM exhibited cytotoxic activity with IC50 values of 73.23 ± 3.06 µg/mL and 31.64 ± 2.75 µg/mL on PC-3 and Hep G2 cell lines, respectively. Being the richest extract in terms of quillaic acid (630 ± 18.9 μg/g), which is a well-known cytotoxic triterpenoid with proven apoptosis induction ability on different cells, FM extract showed apoptosis induction activity with 64.75% on PC-3 cells at 50 μg/mL concentration. The study provides promising results about the potential of Hypericum androsaemum on cancer prevention.

Organic Stimulant Uses In Natural Plant Production

This study focuses on the effects of a commercially available synthetic rooting preparation that includes chemicals of the auxin group with indolebutyric acid (IBA) and natural and organic origin biostimulant on rooting in cuttings, root and twig development. Cuttings of commercially available ornamental plant Trachelospermum jasminoides and potential ornamental plants from natural flora Hypericum calycinum and Hypericum androsaemum were used in the study. The cuttings were kept at a temperature of 24-26 oC and humidity of 80-85% in a greenhouse, perlite environment for 90 days. According to the variance analysis results, the application of biostimulants in T. jasminoides was more effective in cutting rooting rates (69%), whereas there was no difference between the applications in H. calycinum (100%) and H. androsaemum (86.67%) species. As for the number of roots, all applications were equally effective in T. jasminoides (3.86 pieces) and H. androsaemum (2.94 pieces), and biostimulant was the most effective in H. calycinum (8.20 pieces). Biostimulant application in total root length, average root length, main root length, total twig length, average twig length, wet root weight data were found to be at the same level or more effective than the other applications. As a result, this study has found that natural species in flora can be successfully produced by using organic origin biostimulants instead of synthetic preparations for landscape applications.

<p class="Body">A new species, a redescription of Aceria lamii (Liro, 1943) and two new records of eriophyoid mites (Acari: Trombidiformes: Eriophyoidea) on weeds in Golestan province, Iran

During a faunistic survey on eriophyoid mites associated with weeds in Golestan province of Iran, four eriophyoid species were collected. A new species, Aculops hyperisaemum sp. nov., was found on Hypericum androsaemum L. (Hypericaceae) and herein described and illustrated. Paraphytoptus paradoxus Nalepa, 1896, Aceria lamii (Liro, 1943) and Aceria verbenacae de Lillo et al., 2017, were found respectively on Artemisia absinthium L. (Asteraceae), Lamium album L. and Salvia nemorosa L. (Lamiaceae) and are reported for the first time in Iran. Aculops hyperisaemum sp. nov. and A. lamii were vagrant on the underside of the leaves of their host plants and no symptoms were detected. Aceria lamii is redescribed using modern microscopy and terminology. Paraphytoptus paradoxus was vagrant on the leaf underside and caused discoloration of the leaves; this is the first record of Paraphytoptus from Iran. Aceria verbenacae induced erinea on leaves, petioles, stems and flowers on a new host plant species.

The water extract of tutsan (Hypericum androsaemum L.) red berries exerts antidepressive-like effects and in vivo antioxidant activity in a mouse model of post-stroke depression

Hypericum androsaemum L., commonly known as ‘tutsan’ or ‘shrubby St. John’s Wort’, is a member of the Hypericum genus found growing spontaneously in the Mediterranean area and is cultivated extensively as an ornamental plant due to the showy color variation in its fresh berry-like capsules, which turn from red to shiny black as they ripen. Tutsan has also been used in Portuguese and Spanish folk medicine to treat depression. In this study, we assessed the beneficial role of the water extract of H. androsaemum red berries (WE) in an experimental animal model of post-stroke depression. WE was obtained by decoction of H. androsaemum red berries, and its content of ten bioactive compounds was determined through HPLC-DAD analysis. Behavioral tests were carried out using a mouse model of post stroke depression to examine the antidepressive-like activity of WE at two doses (15 and 30 mg/kg bw). In addition, the in vivo antioxidant activity in the mouse brain was evaluated by measuring CAT, GSH, and SOD activity and TBARS levels. WE contained significant amounts of shikimic acid (110.0 g/kg), chlorogenic acid (56.9 g/kg), catechin (5.8 g/kg) and hyperoside (2.7 g/kg). Overall, the highest dosage of WE was found to significantly reduce the symptoms of depression, restoring normal behaviour and reducing levels of oxidative stress by increasing endogenous antioxidant defenses. The protective effects of WE in post-stroke depression in a mouse model were demonstrated in vivo for the first time, and correlated with the antioxidant capacity of its bioactive constituents.

Phytochemical analysis and ethno-pharmacological importance of the fruits of Hypericum androsaemum L.

Phytochemical analysis and ethno-pharmacological importance of the fruits of Hypericum androsaemum L.

Polar extracts from the berry-like fruits of Hypericum androsaemum L. as a promising ingredient in skin care formulations

Ethnopharmacological relevanceThe top flowering aerial parts of the Hypericum species are traditionally used to prepare ointments to heal cuts and burns. Sometimes even the fruits are used for these purposes. Hypericum androsaemum L., commonly known as tutsan or shrubby St. John's Wort, is a Mediterranean medicinal plant which has been traditionally used to prepare an ointment for treating cuts and wounds. Aim of the studyTo evaluate the extracts obtained from H. androsaemum red berries as functional ingredients for skin care formulations. Materials and methodsThe methanolic extract was obtained by Soxhlet extraction while the aqueous extract was prepared by decoction; their composition was determined by HPLC analysis. Their biological activities were measured in terms of proliferation and migration of human fibroblasts, inhibition of collagenase activity, and immunomodulatory effects on human peripheral blood mononuclear cells (PBMCs). In addition, we evaluated their photostability by UV spectroscopy and their protective effects against APPH-induced hemolysis in red blood cells (RBC). ResultsThe polar extracts contained significant amounts of shikimic (108,143.7–115,901.3mg/kg) and chlorogenic acids (45,781.1–57,002.7mg/kg). The main components of these extracts made an important contribution to a significant increase in human fibroblast migration. Both extracts were also active as collagenase inhibitors, with the aqueous one showing a greater inhibitory capacity (IC50 value of 88.1µg/mL), similar to that of chlorogenic acid. The kinetic parameters determined for the enzymatic reaction revealed for both aqueous extract and chlorogenic acid an uncompetitive mechanism of inhibition. The methanolic extract showed important effects on PBMCs by modulating IL-6. Both extracts proved to be photostable in the UVA/B range and protected RBC against peroxidation at low concentrations. ConclusionsH. androsaemum red berries were proven to contain phytochemicals that improve skin regeneration, hence potentially employable in skin care formulations.

Methanolic extract from red berry-like fruits of Hypericum androsaemum: Chemical characterization and inhibitory potential of central nervous system enzymes

Hypericum androsaemum is an evergreen shrub spread in the Mediterranean basin and cultivated in several European countries. The plant bears fleshy and berry-like capsules that ripen from red to shiny black. In several European conutries H. androsaemum has been traditionally used as diuretic, hepatoprotective, wound healing and as an antidepressant agent. The aim of the study was to evaluate the pharmaceutical potential of the methanolic extract of H. androsaemum red berries (HASE) through inhibition of CNS enzymes such as monoamine oxidase A (MAO-A), tyrosinase (TYR) and acetylcholinesterase (AChE). HASE was obtained by soxhlet extraction and analysed by HPLC-DAD for the content of ten bioactive constituents. HASE activities were measured in terms of monoamine oxidase A (MAO-A), tyrosinase (TYR) and acetylcholinesterase (AChE) inhibition. HASE was very rich of shikimic acid and chlorogenic acid, occurring at concentration of 94941.7 and 39059.1mg/kg, respectively. HASE was able to inhibit MAO-A and TYR in a dose dependent manner, although activity was not superior to positive control substances. On the basis of HASE composition and inhibitory effects on MAO-A and tyrosinase, red berries might represent an alternative Hypericum to obtain pharmacologically active substances.

Bioactive properties and functional constituents of Hypericum androsaemum L.: A focus on the phenolic profile

Hypericum androsaemum L. ethanol:water extract acted as a lipid peroxidation inhibitor and free radical scavenger. A marked inhibition of the growth of breast, lung, cervical and hepatocellular human carcinoma cell lines was also observed, whereas no toxicity was shown against non-tumor porcine liver cells (>400μg/mL). The extract was also effective in inhibiting nitric oxide production, as an indicator of the anti-inflammatory potential. The anti-Candida effects varied among different strains of the same species, C. glabrata and C. tropicalis being the most sensible species with an effect directly related with the extract concentrations tested. A significant anti-biofilm formation potential was also observed, namely for C. glabrata and C. tropicalis (biofilm reduction >90%). 5-O-Caffeoylquinic and 3-O-caffeoylquinic acids were the most abundant phenolic compounds identified in the extract, and might be related with the observed bioactive effects. Nevertheless, future studies should be carried out to obtain dose-response curves of the isolated active compounds, in order to perform further pre-clinically testing to quantify the presence of the most active compounds in the extract.

Benzophenone Synthase and Chalcone Synthase Accumulate in the Mesophyll of Hypericum perforatum Leaves at Different Developmental Stages.

The active medicinal constituents in Hypericum perforatum, used to treat depression and skin irritation, include flavonoids and xanthones. The carbon skeletons of these compounds are formed by chalcone synthase (CHS) and benzophenone synthase (BPS), respectively. Polyclonal antisera were raised against the polyketide synthases from Hypericum androsaemum and their IgG fractions were isolated. Immunoblotting and immunotitration were used to test the IgGs for crossreactivity and monospecificity in H. perforatum leaf protein extract. Immunofluorescence localization revealed that both CHS and BPS are located in the mesophyll. The maximum fluorescence levels were observed in approx. 0.5 and 1 cm long leaves, respectively. The fluorescence intensity observed for CHS significantly exceeded that for BPS. Using histochemical staining, flavonoids were detected in the mesophyll, indicating that the sites of biosynthesis and accumulation coincide. Our results help understand the biosynthesis and underlying regulation of active H. perforatum constituents.

Polar Constituents and Biological Activity of the Berry-Like Fruits from Hypericum androsaemum L.

Hypericum androsaemum, also known as Tutsan, is a small evergreen shrub common in the Mediterranean basin where it is traditionally used as diuretic and hepatoprotective herbal drug. This plant possesses the peculiarity to produce fleshy and berry-like fruits that ripen from red to shiny black. In the present work, the chemical constituents of methanolic extracts and infusions of red and black fruits were analyzed by HPLC, and correlated with their antioxidant properties which were evaluated by the DPPH, β-Carotene/linoleic acid, and hypochlorous acid tests. In addition, the red pigment of the fruit was isolated by column chromatography and structurally elucidated by NMR. Results showed that H. androsaemum fruits contain high amounts of shikimic and chlorogenic acids, while their color was given by a tetraoxygenated-type xanthone, reported for the first time in Hypericum species. The red berries infusion gave the highest content of total phenolic compounds, DPPH, and hypochlorous acid scavenging activity, and β-carotene bleaching. Cytotoxicity of the berries extracts on three human tumor cell lines (malignant melanoma, breast adenocarcinoma, and colon carcinoma) was evaluated by MTT assay, and relevant inhibition on colon carcinoma cells (IC50 value of 8.4 μg/mL) was found. Finally, the effects of red berries extract on the immune system were evaluated by peripheral blood mononuclear cell (PBMC) proliferation assay that revealed a strong stimulation on lymphocytes at low doses (0.4–6 μg/mL).

Comparative study on the in vivo antidepressant activities of the Portuguese Hypericum foliosum, Hypericum androsaemum and Hypericum perforatum medicinal plants

The aerial part of Hypericum foliosum showed similar major classes of constituents to Hypericum perforatum. However, H. foliosum belongs to Androsaemum section, as Hypericum androsaemum, characterized by absence of hypericins. To compare the in vivo antidepressant activity of methanol extracts from aerial part of these three species, based on fact of methanol extracts were the most used on antidepressant H. perforatum medicines. FST and TST in mice were used. H. foliosum active extract was fractionated and the antidepressant activity of the fractions was evaluated. Additionally, in vivochronic toxicity of this extract was determined. H. foliosum extract (500mg/kg, p.o.) produced a significant reduction of the immobility time in TST. Concerning the tendency to decrease this immobility time with H. androsaemum and H. perforatum, no statistically significant differences were observed between both extracts mentioned and the control groups. Using FST no immobility time reduction was observed by administration of the different extracts. H. foliosum fractions showed also to be inactive at a dose of 250mg/kg, p.o. in both tests. H. foliosum extract (1000mg/kg) had no significant toxicity for liver, kidney or pancreas. Quinic acid, 3,4-dimethylbenzoic acid, (+) catechin, chlorogenic acid, quercetin-3-O-sulphate, miquelianin, xanthone and amentoflavone were identified as marker compounds of H. foliosum extract and methanol fraction. Phloroglucinol derivatives were detected in the diethylether fraction of this active extract. This study provides the first evidence indicating that the extract of H. foliosum has an antidepressant effect in a predictive animal model of antidepressant properties, the TST.

Volatile profile, nutritional value and secretory structures of the berry-like fruits of Hypericum androsaemum L

Hypericum androsaemum, also known as Tutsan, produces fleshy and berry-like fruits that ripen from red to shiny black. The essential oil and aroma components of the red and black berries were investigated by GC–FID, GC–MS, and HS-SPME–GC–MS. The nutritional profile of the red and black berries in terms of proteins, carbohydrates, crude fiber, ascorbic acid, mineral content and fatty acid composition was also investigated. Finally, the morphological and histochemical study of fruits identified the histolocalization of the complex metabolite mixture produced. Results showed that monoterpene hydrocarbons gave the major contribution to the fruit aroma, with limonene as the most representative compound, even though some differences were found between red and black berries. Nutritional analysis highlighted a relevant content of ascorbic acid (135.7mg/100g) in red berries. The morphological and histochemical analysis showed that the fruit secretion is produced in numerous translucent glands that originated from the ovarian mesophyll and arranged in concentric rings.

Cytotoxic activity of water extract fractions of Hypericum androsaemum L. on colorectal cancer cells

Hypericum androsaemum L. (HA) grows wild in shadowy sites, namely in northern region of Portugal, where it is widely used as a medicinal herb. According to some authors, this species is used in popular medicinal preparations as a cholagogue, hepatoprotector, and diuretic and in kidney failure [1]. In this work, the composition of water soluble and volatile components of HA infusions was characterized and the total extract (HA-T) fractioned in order to identify the active compound(s) responsible for their cytotoxic effects. HA-T and each of its seven fractions (HA-A to HA-G) were tested against CO115 cells, at 40 µg/mL. Effects on cell viability/proliferation and apoptosis were assessed by MTT and nuclear condensation assays, respectively. The expression of intermediates of the MAPK/ERK and PI3K/AKT signalling pathways and the expression of apoptotic markers were evaluated by western blot. HA-E and F showed decreases in cell viability in relation to control. Of these fractions, only HA-F showed to slightly increase apoptosis. The effects of individual fractions did not explain the 40% apoptosis reached in response to the total and the reconstituted extract, suggesting that the synergistic effects of the extract's constituents are needed for the HA cytotoxic properties against the CO115 cells. In agreement with this, only HA-T showed significant increases in the apoptotic markers cleaved caspase-9 and cleaved PARP-1. Relative to the total extract (HA-T), only slight decreases in BRaf (HA-E), pERK (HA-E) and pAKT (HA-E and HA-F) were observed. Only HA-T reduced significantly the expression of BRaf, pErk and pAKT. These results support the hypothesis that there is more than one compound in the HA-T responsible for the HA toxicity on the colorectal cancer cells.

Involvement of PKA, but not Epac, in flavonoid accumulation in cell cultures of Hypericum androsaemum

Involvement of PKA, but not Epac, in flavonoid accumulation in cell cultures of Hypericum androsaemum

HRM analysis targeting ITS1 and matK loci as potential DNA mini-barcodes for the authentication of Hypericum perforatum and Hypericum androsaemum in herbal infusions

Hypericum species are among the medicinal plants that are being increasingly used due to their reported health benefits. Hypericum perforatum (St. John's wort) is well known for its anti-inflammatory, anti-depressive and anti-viral properties, as well as a healing agent. In Portuguese folk medicine, Hypericum androsaemum (Hipericão do Gerês) is largely used for its hepatic protective and diuretic properties. This work aimed at searching the potential use of two DNA mini-barcode candidates (ITS1 and matK) for the authentication of H. perforatum and H. androsaemum in herbal infusions. The sequencing results from ITS1 and matK regions were the basis for the development of species-specific PCR and real-time PCR assays coupled to High Resolution Melting (HRM) analysis, as simple approaches for the reliable discrimination of both species. The barcode regions were successful in the species-specific PCR identification of each target. ITS1 region revealed some intra-species variability from sequencing results, which compromises HRM analysis, while matK showed to be an adequate mini-barcode for the differentiation of both species by real-time PCR coupled to HRM analysis. The assays were effectively applied to commercial herbal infusions, enabling the consistent identification of two labels with non-declared Hypericum species.