Hypericum Perforatum Extract Research Articles

Impacts of manganese bio-based nanocomposites on phytochemical classification, growth and physiological responses of Hypericum perforatum L. shoot cultures

We report a new green route for preparing MnO2/perlite nanocomposites (NCs) by leaf extract of Hypericum perforatum. Characterization of the physicochemical properties of the MnO2/perlite-NCs was performed using XRD, FESEM, EDX, FT-IR, and DLS techniques. Furthermore, their effects on the phytochemical classification and growth parameters of H. perforatum shoot cultures were assessed. According to the FESEM image, the synthesized spherical MnO2 nanoparticles on the sheet-like structure of nano-perlite were formed, ranging about 20–50 nm. In addition, based on the EDX spectra, the elemental analysis showed the presence of Carbon, Oxygen, Silicon, Aluminum, and Manganese elements in the as-synthesized MnO2/perlite-NCs. Biological studies confirmed that nano-perlite and MnO2/perlite-NCs were non-toxic to H. perforatum shoot cultures and showed positive effects on plant growth in specific concentrations. Overall, phytochemical classification demonstrated that the terpenoids decreased in the evaluated treatments, while hypericin and pseudohypericin were increased in some treatments (25, 50 and 150 mg/L of nano-perlite) relative to control. Metabolomics results suggested that both nano-perlite and MnO2/perlite-NCs can be used as elicitors and new nanofertilizers for generating some secondary metabolites.

Efficacy of Hypericum perforatum extract on ultrastructural changes in brain and oxidative damage in Parkinson’s disease

Parkinson’s disease (PD) is a serious chronic and progressive neurological disorder. Hypericum perforatum (H. perforatum) is a plant generally used as an antidepressant and therapy for many neurodegenerative disorders. The present study evaluates the action of Hypericum perforatum extract on MPTP induced oxidative stress and ultrastructural changes in the Parkinson disease model. For this research study, Parkinson disease in mice were induced using MPTP and Hypericum perforatum methanolic extract were given in the pre-treatment and post-treatment condition. After the treatment, the oxidative stress was measured using TBARS levels and the activities of GSH, GPx, CAT and SOD in brain tissues. The ultrastructural changes in brain mitochondria caused by MPTP toxicity was studied after Hypericum perforatum extract therapy using TEM images. The present study showed that HPE extract is able to balance the oxidative stress and antioxidants in the brain tissue of MPTP administered rats. The damaged nuclei in the brain recovered to the normal condition due to this extract therapy. Finally, to conclude, Hypericum perforatum extract post-treatment offers potential brain protection against MPTP-induced Parkinson’s disease than pre-treatment.

Protective Role of St. John's Wort and Its Components Hyperforin and Hypericin against Diabetes through Inhibition of Inflammatory Signaling: Evidence from In Vitro and In Vivo Studies.

Diabetes mellitus is a very common chronic disease with progressively increasing prevalence. Besides the well-known autoimmune and inflammatory pathogenesis of type 1 diabetes, in many people, metabolic changes and inappropriate lifestyle favor a subtle chronic inflammatory state that contributes to development of insulin resistance and progressive loss of β-cell function and mass, eventually resulting in metabolic syndrome or overt type 2 diabetes. In this paper, we review the anti-inflammatory effects of the extract of Hypericum perforatum L. (St. John’s wort, SJW) and its main active ingredients firstly in representative pathological situations on inflammatory basis and then in pancreatic β cells and in obese or diabetic animal models. The simultaneous and long-lasting inhibition of signal transducer and activator of transcription (STAT)-1, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPKs)/c-jun N-terminal kinase (JNK) signaling pathways involved in pro-inflammatory cytokine-induced β-cell dysfunction/death and insulin resistance make SJW particularly suitable for both preventive and therapeutic use in metabolic diseases. Hindrance of inflammatory cytokine signaling is likely dependent on the hyperforin content of SJW extract, but recent data reveal that hypericin can also exert relevant protective effects, mediated by activation of the cyclic adenosine monophosphate (cAMP)/protein kinase cAMP-dependent (PKA)/adenosine monophosphate activated protein kinase (AMPK) pathway, against high-fat-diet-induced metabolic abnormalities. Actually, the mechanisms of action of the two main components of SJW appear complementary, strengthening the efficacy of the plant extract. Careful quantitative analysis of SJW components and suitable dosage, with monitoring of possible drug–drug interaction in a context of remarkable tolerability, are easily achievable pre-requisites for forthcoming clinical applications.

Hypericum perforatum extract and hyperforin inhibit the growth of neurotropic parasite Toxoplasma gondii and infection-induced inflammatory responses of glial cells in vitro

Ethnopharmacological relevanceHypericum perforatum L. has been widely used as a natural antidepressant. However, it is unknown whether it is effective in treating infection-induced neuropsychiatric disorders. Aim of the studyIn order to evaluate the effectiveness of H. perforatum against infection with neurotropic parasite Toxoplasma gondii, which has been linked to neuropsychiatric disorders, this study investigated the anti-Toxoplasma activity using in vitro models. Materials and methodsDried alcoholic extracts were prepared from three Hypericum species: H. perforatum, H. erectum, and H. ascyron. H. perforatum extract was further separated by solvent-partitioning. Hyperforin and hypericin levels in the extracts and fractions were analyzed by high resolution LC-MS. Anti-Toxoplasma activities were tested in vitro, using cell lines (Vero and Raw264), murine primary mixed glia, and primary neuron-glia. Toxoplasma proliferation and stage conversion were analyzed by qPCR. Infection-induced damages to the host cells were analyzed by Sulforhodamine B cytotoxicity assay (Vero) and immunofluorescent microscopy (neurons). Infection-induced inflammatory responses in glial cells were analysed by qPCR and immunofluorescent microscopy. ResultsHyperforin was identified only in H. perforatum among the three tested species, whereas hypericin was present in H. perforatum and H. erectum. H. perforatum extract and hyperforin-enriched fraction, as well as hyperforin, exhibited significant anti-Toxoplasma property as well as inhibitory activity against infection-induced inflammatory responses in glial cells. In addition, H. perforatum-derived hyperforin-enriched fraction restored neuro-supportive environment in mixed neuron-glia culture. ConclusionsH. perforatum and its major constituent hyperforin are promising anti-Toxoplasma agents that could potentially protect neurons and glial cells against infection-induced damages. Further study is warranted to establish in vivo efficacy.

Effects of Hypericum perforatum (St John's wort) on the pharmacokinetics and pharmacodynamics of rivaroxaban in humans.

To investigate the influence of a cytochrome P450 CYP3A4 and efflux transporter P-glycoprotein (P-gp) inducing Hypericum perforatum extract on the pharmacokinetics and pharmacodynamics of rivaroxaban. Open-label, nonrandomized, sequential treatment interaction study. Following CYP3A4 and P-gp phenotyping using low-dose midazolam and fexofenadine, 12 healthy volunteers received a single oral dose of 20 mg rivaroxaban and rivaroxaban plasma concentrations and inhibition of the activated coagulation factor X (factor Xa) activity were measured prior to and up to 48 h postdosing. The procedures were repeated after 2 weeks' treatment with the H. perforatum extract. The geometric mean ratios for the area under the concentration-time curve and Cmax of rivaroxaban after/before induction with the H. perforatum extract were 0.76 (90% confidence interval [CI] 0.70, 0.82) and 0.86 (90% CI 0.76, 0.97), respectively. Inhibition of factor Xa activity was reduced with a geometric mean area under the effect-time curve ratio after/before induction of 0.80 (90% CI 0.71, 0.89). No clinically significant differences were found regarding Tmax (median 1.5 vs 1 h, P = .26) and terminal elimination half-life (mean 10.6 vs 10.8 h, P = .93) of rivaroxaban. The H. perforatum extract significantly induced CYP3A4 and P-gp activity, as evidenced by phenotyping. The CYP3A4/P-gp inducing H. perforatum extract caused a decrease of rivaroxaban exposure with a proportional decrease of the pharmacodynamic effect. Although the data do not justify a contraindication for the combination or a systematic adjustment of rivaroxaban dosage, avoidance of the combination or laboratory monitoring should be considered in patients taking hyperforin-containing H. perforatum extracts with rivaroxaban.

Gastroprotective activity of Hypericum perforatum extract in ethanol-induced gastric mucosal injury in Wistar rats: A possible involvement of H+/K+ ATPase α inhibition

Hypericum perforatum (HP) is a plant native to Asia and Europe. It has been documented to enclose medical effects against many disorders such as anxiety, depression and burns. This experiment was performed to evaluate the gastro-protective effect of Hypericum perforatum leaf extract in ethanol induced gastric ulcer in rats as compared to esomeprazole (the drug of choice for stomach ulcers). The mechanism of action was performed by Auto Dock Vina method.Ethanol ingestion up regulated the inflammatory reaction as demonstrated by rise of gastric proinflammatory TNF-α with a decline of IL-1β. On the other hand, the phytochemical screening of HP revealed the presence of alkaloids, flavonoids, tannins, phenols, steroids and saponins. The high dose of HP group shows mild injuries to the gastric mucosa which is comparable to the esomeprazole group, in contrast, severe damages are observed in the gastric mucosa of the ulcer control rats group. In silico results revealed that Amentoflavone and Quercitrin have highest affinity and very good interactions with H+/K+ ATPase α active site. This study showed that HP is nearly as effective as esomeprazole to prevent ethanol induced gastric ulcer the plant extract and it has more binding affinity than esomeprazole to gastric proton pumps.

In Vivo Investigation of Genotoxic and Antigenotoxic Potential of Hypericum Perforatum Extract in Rats

This study was planned to reveal in vivo genotoxic, antigenotoxic and cytotoxic properties of methanolic extracts of St. John's Wort plant (Hypericum perforatum). The methanol extract of H. perforatum was administrated to rats alone or in combination with N-nitrosodimethylamine and Triclosan (positive control). The concentrations of H. Perforatum were 20, 100, 500 mg/kg and the period of administration was 30 days. At the end of this period, chromosome aberration test used to determine genotoxic and antigenotoxic effects of H. perforatum. In addition, total oxidant and antioxidant levels of peripheral blood serum of rats were determined by spectrophotometric method. According to our result, H. perforatum extract did not demonstrate genotoxic effect at concentrations administrated. When compared to the negative control, the percentage of abnormal cells was increased in groups treated with test substance, N-nitrosodiethylamine and triclosan together. However, these increases were not as higher as groups treated with N-nitrosodiethylamine plus triclosan (positive control). Even, in groups treated with the test substance additional N-nitrosodiethylamine plus triclosan, the ratio of abnormal cells was inversely proportional to the increase in the concentration. The lowest ratio of abnormal cells was in the group in which the highest concentration of the H. perforatum (500 mg/kg) was applied. The highest two concentrations of the H. perforatum (100 and 500 mg/kg) significantly increased the mitotic index. In the group treated with test substance and positive control together, the mitotic index was even greater. At the same time 100 mg/kg of H. perforatum extract significantly reduced the oxidative stress.

Improving the phytochemical profile and bioactivity of Chinese cabbage sprouts by interspecific transfer of metabolites

The high demand for healthy food in recent years has led to an increasing need for highly bioactive plant materials. One such plant, Chinese cabbage, possesses flavonoids with antioxidant and antidiabetic properties, but they appear in low quantities. The interspecific transfer of metabolites is a promising technique that could contribute to the increase of the beneficial properties of food. The objective of the study was to determine how an interspecific source-sink phytochemical transfer from donor extracts to the Chinese cabbage affects its phenolic and vitamin C profile and intestinal bioaccessibility, hypoglycemic potential and antioxidant capacity. In addition, sprouts treated with Rosa sp. and Hypericum perforatum extracts showed better antiproliferative effect towards human breast adenocarcinoma cells than untreated sprouts. The results suggest that treatment of plants with donor extracts is a promising approach to improve the nutritional and phytochemical profile and bioactive properties of acceptor plants.

Oregano (Origanum vulgare), St John's-wort (Hypericum perforatum), and lemon balm (Melissa officinalis) extracts improved the growth rate, antioxidative, and immunological responses in Nile tilapia (Oreochromis niloticus) infected with Aeromonas hydrophila

The present study was designed to evaluate the effects of ethanolic extracts of Hypericum perforatum (HP), Origanum vulgare (ORG), and Melissa officinalis (MOF) on Nile tilapia (Oreochromis niloticus) juveniles. Fish (16.92 ± 0.28 g) were randomly divided into seven groups fed on diets with 0 % (CTR), and two levels (0.2 % and 0.5 %) from each plant extract for 60 days. Final body weight, weight gain %, specific growth rate, and feed conversion ratio were significantly improved in the groups fed with ORG and MOF at 0.5 % (P < 0.05). Moreover, ORG 0.5 % and MOF 0.5 % groups showed a significant increase in RBCs and WBCs counts as well as the hematocrit and hemoglobin values (P < 0.05). Besides, significant enhancement was noticed in the levels of intestinal digestive enzymes in the MOF 0.5 % group (P < 0.05). Activities of hepatic superoxide dismutase, glutathione peroxidase, catalase were significantly improved, meanwhile, the hepatic malondialdehyde levels were significantly decreased in all groups fed on phytogenic diets compared to the CTR group (P < 0.05). Furthermore, ORG 0.5 % and MOF 0.5 % groups showed a significant increase in serum total protein, and alternative complement activity (ACH50) (P < 0.05). Attractively, serum lysozyme levels were significantly increased while serum endotoxin values decreased in all groups fed on phytogenic diets. Furthermore, the MOF 0.5 % group showed the highest activities of skin mucus lysozyme, ACH50, and protease (P < 0.05), meanwhile mucosal total immunoglobulins were the highest in ORG 0.5 % and both levels of MOF. ORG 0.5 % and MOF 0.5 % groups showed the highest protection levels of fish following challenge with pathogenic Aeromonas hydrophila. Conclusively, this comparative study showed that both ORG and MOF extract at a 0.5 % level can effectively improve the growth, health, and immune status of Nile tilapia juveniles.

Protective Effect of Hypericum perforatum Extract on Methotrexate-Induced Osteotoxicity via Reducing Oxidative Stress and MAPK Activity

Protective Effect of Hypericum perforatum Extract on Methotrexate-Induced Osteotoxicity via Reducing Oxidative Stress and MAPK Activity

Chemical composition, antioxidant activity, standardization and kinetics of production of water-propylene glycol extracts of medicinal plants

Water-propylene glycol extracts of medicinal plants are widely used as active components in therapeutic and cosmetic products for external use. However, sparse data on the extracting efficiency of water-propylene glycol mixtures and chemical composition of water-propylene glycol extracts of plant raw materials are available in the scientific literature. Usually the manufacturer documentation also provides information about characteristics of the products that are not related to their biological activity. The results of HPLC/MS/MS study of Matricaria chamomilla L. flowers have shown that water-propylene glycol and water-ethanol extracts are similar in the composition of phenolic compounds: the dominant compounds of water-propylene glycol extract of Matricaria chamomilla L. flowers are apigenin and its glycosides (apigenin-7-glucoside, apigenin-7-O-6-O-malonyl-D-glycoside, apigenin-7-acetylglycoside, acetyl-malonyl-apigenin-7-O-glycoside), as well as 5,4’-dioxy-3,6,7,3’-tetramethoxyflavone, cis- and trans-forms of 2-O-glucopyranoside 2-hydroxy-4-methoxycoric acid, 7-methoxycumarin. Spectral and analytical characteristics in the UV-visible range of the spectra of water-propylene glycol extracts of a number of medicinal plants most often used in the cosmetic industry were studied to reveal extracts with the highest protective properties against UV radiation in A and B areas (extracts of Salvia officinalis L. leaves, Matricaria chamomilla L. flowers, Achillea millefolium L. grass), free radicals (extracts of Camellia sinensis L. leaves, Hypericum perforatum L. herb), and the highest content of flavonoids (extracts of Hypericum perforatum L. herb, leaves of Salvia officinalis L.) were revealed. When extracting raw materials from the same batch, the optical density at a wavelength of 270 nm is associated with the content of flavonoids, antioxidants and dry matter by a functional relationship, which is very convenient for rapid control of extraction processes in order to obtain a product with reproducible characteristics. Formulas for calculating the content of antioxidants in extracts using the DPPH method in comparison with standard samples of rutin and gallic acid are derived. Interpretation of data on the antioxidant content in different extracts in comparison with other analytical parameters are also presented. Demonstrated high repeatability of the shape of the spectral curves of Matricaria chamomilla L. flowers extract, observed regardless of the source of raw materials can be used in combination with the individuality of the curve shape of the extracts of raw materials of different types as one of the authenticity criteria. The proposed UV-spectrometric method was used to study the dynamics of Matricaria chamomilla L. flower extraction under different process parameters (temperature, propylene glycol/water ratio in the extractant). It is shown that extraction of raw materials with 50% water-propylene glycol for 4 h at a temperature of 50°C is optimal.

Proapoptotic Effect of Hypericum perforatum (St. John's Wort) Extract in Human Colorectal Adenocarcinoma Cell Line HT29

Proapoptotic Effect of Hypericum perforatum (St. John's Wort) Extract in Human Colorectal Adenocarcinoma Cell Line HT29

Effect of Extraction Conditions on the Phenolic Content and DPPH Radical Scavenging Activity of Hypericum perforatum L.

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

Improve cognition of depressive patients through the regulation of basal ganglia connectivity: Combined medication using Shuganjieyu capsule

Shuganjieyu capsule (Shugan) is a combined extract of Hypericum perforatum (HP) and Eleutherococcus senticosus (ES). Both HP and ES have been proven effective in the treatment of depression and impaired cognition. However, for mild to moderate depression (MMD), the treatment effect and underlying mechanism by combining both HP and ES are largely unknown. Here, we aim to evaluate the therapeutic effects on impaired cognition using Shugan, a combined medication of HP and ES. Resting-state magnetic resonance imaging (MRI) data and cognitive assessment have been collected from 54 healthy controls and 55 MMD patients that have been undergoing 8-week Shugan-treatment. The functional connectivity (FC) and brain region volume changes of the basal ganglia seeded circuit have been measured, and their relation with the cognitive assessment score was calculated. After that, a literature-based pathway analysis has been conducted to explore the biological relations among Shugan, brain regions, and depression. Compared to healthy controls, MMD patients demonstrated a significantly higher FC (P= 0.0025) between right ventral caudate (vCa) and left orbitofrontal cortex (OFC), which was decreased after the treatment (P < 0.001). A volume of the right caudate, which is increased in MMD, has also been reduced by Shugan treatment (P= 0.017). Importantly, the cognitive scores were strongly correlated with both Shugan treatment and the FC between vCa and OFC (r= 0.321, P= 0.02). Besides, we identified multiple signaling pathways, through which Shugan might improve the cognition of MMD patients. Our results support the therapeutic effects of Shugan on cognition in MMD, which may be realized partly through the regulation within two brain regions, vCa and OFC.

Inhibitory effects of different medicinal plants on growth of some oral microbiome member

Oral infections and dental caries are still considered as a serious public health problem. Using the method of minimum inhibitory concentrations (MICs), the aim of this study was to investigate the inhibitory effects of 16 plants on the growth of Actinomyces odontolyticus, Streptococcus mitis, Streptococcus sanguinis, Eikenella corrodens, Fusobacterium nucleatum, Lactobacillus acidophilus and Streptococcus mutans. The most effective were ethanol extracts of Rosmarinus officinalis, Salvia officinalis, Thymus vulgaris, Calendula officinalis and Hypericum perforatum. The least efficiency was observed for Acorus calamus extract. Plant extracts could be used in oral health as therapeutic and prophylactic approach or in balancing oral microbiota.

An extract of Hypericum perforatum induces wound healing through inhibitions of Ca2+ mobilizations, mitochondrial oxidative stress and cell death in epithelial cells: Involvement of TRPM2 channels

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Investigation of Apoptotic Effects of Hypericum perforatum Extract on Breast Cancer Cell Line

Hypericum perforatum has biological active contents affecting a variety of proteins such as caspase-3, bcl-2, and bax, which mediate apoptosis known as programmed cell death and exerting anti-inflammatory effect. Apoptotic pathways are important for cancers, chemotherapeutic resistance, and cancer development. Anti-inflammatory agents are also a potential target for cancer. Therefore, it was aimed to investigate the activity of caspase-3 and the expressions of bcl-2, bax, wee 1, gadd153, grp78, AIF, iNOS, COX-2, cPLA2, and NF-κB in H. perforatum extract-treated breast cancer (BC) cells in this study. The activity of caspase-3 and the expressions of these proteins were determined in the cells by ELISA. The HP extract increased the activity of caspase-3 and the expressions of bax, wee 1, gadd153, grp78 and AIF, and decreased the expressions of bcl-2, COX-2, iNOS, cPLA2 and NF-κB in the BC cells. In the light of these findings, HP extract could help to inhibit grow of BC cells and its anti-inflammatory effect may contribute this effect.

Antimicrobial Photoinactivation Using Visible Light Plus Water-Filtered Infrared-A (VIS\u2009+\u2009wIRA) and Hypericum Perforatum Modifies In Situ Oral Biofilms

Due to increasing antibiotic resistance, the application of antimicrobial photodynamic therapy (aPDT) is gaining increasing popularity in dentistry. The aim of this study was to investigate the antimicrobial effects of aPDT using visible light (VIS) and water-filtered infrared-A (wIRA) in combination with a Hypericum perforatum extract on in situ oral biofilms. The chemical composition of H. perforatum extract was analyzed using ultra-high-performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS). To obtain initial and mature oral biofilms in situ, intraoral devices with fixed bovine enamel slabs (BES) were carried by six healthy volunteers for two hours and three days, respectively. The ex situ exposure of biofilms to VIS + wIRA (200 mWcm−2) and H. perforatum (32 mg ml−1, non-rinsed or rinsed prior to aPDT after 2-min preincubation) lasted for five minutes. Biofilm treatment with 0.2% chlorhexidine gluconate solution (CHX) served as a positive control, while untreated biofilms served as a negative control. The colony-forming units (CFU) of the aPDT-treated biofilms were quantified, and the surviving microorganisms were identified using MALDI-TOF biochemical tests as well as 16 S rDNA-sequencing. We could show that the H. perforatum extract had significant photoactivation potential at a concentration of 32 mg ml−1. When aPDT was carried out in the presence of H. perforatum, all biofilms (100%) were completely eradicated (p = 0.0001). When H. perforatum was rinsed off prior to aPDT, more than 92% of the initial viable bacterial count and 13% of the mature oral biofilm were killed. Overall, the microbial composition in initial and mature biofilms was substantially altered after aPDT, inducing a shift in the synthesis of the microbial community. In conclusion, H. perforatum-mediated aPDT using VIS + wIRA interferes with oral biofilms, resulting in their elimination or the substantial alteration of microbial diversity and richness. The present results support the evaluation of H. perforatum-mediated aPDT for the adjunctive treatment of biofilm-associated oral diseases.

Effect of Hypericum Perforatum L Extracts on depression induced by chronic unpredictable mild stress in mice

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). 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. Key words: Hypericum perforatum L; Depression; Stress; Forced swimming; Brain-derived neurotrophic factor; Mice

Effects of hypericum perforatum extract on the immunogenic myocardial fibrosis in mice and its mechanism

To study the effects of hypericum perforatum extract (HPE) on myocardial fibrosis of the experimental autoimmune myocarditis (MFEAM) in mice. MFEAM model of immunosuppressive mouse was established by porcine cardiac myosin. The mice in the MFEAM model group were randomly divided into: MFEAM model group (n=14), HPE 100 mg/kg group (n=13), HPE 40 mg/kg group (n=13) and captopril (Cap) 50 mg/kg control group (n=13). Drug in each group was dissolved in 0.4 ml of physiological saline each time, and administered by intragastric administration twice a day for 60 days; the normal control group (n=10) and the MFEAM model group was given normal saline at the same volume and course of treatment as above described way. The ratio of heart weight and spleen weight to body weight were calculated, the general conditions of mice were observed. The contents of procollagen I N-terminal peptide(PINP), procollagen III N-terminal peptide (PIIINP) and TGF-β1 in serum of mice were detected. The degree of myocardial fibrosis (MF) and collagen volume fraction (CVF)were measured under the microscope by Masson staining. The protein expression of TGF-β1 was detected by Western blot. The serum levels of TGF-β1, PINP and PIIINP in the model group were higher than those in the normal group significantly (P＜0.05 or P＜0.01). Meanwhile , the levels of MF and CVF were increased, and the protein expression of myocardial TGF-β1 was up-regulated. However, the serum levels of PINP, PIIINP and TGF-β1 in HPE40 mg/kg, HPE 100 mg/kg and Cap treated-groups were decreased significantly. HPE and Cap could improve or decrease the MF level and CVF of the MFEAM model mice, and down-regulated the expression of TGF-β1 protein in different degrees. Compared with the MFEAM model group, the difference was significant (P＜0.05 or P＜0.01). HPE has a therapeutic effect on MF, which may be related to its reduction of collagen deposition and inhibition of TGF-β1 signaling pathway.