hypericum and Disease-Models--Animal

Insufficient sleep, insomnia, and sleep-related problems are important health issues, as their overall prevalence accounts for about 30% of the general population. The aim of this study was to systematically review previous studies investigating the effects of orally administered single plant-derived extracts on sleep-related outcomes in humans. Data sources were PubMed, Google Scholar, and Cochrane Library. The data search was conducted in two steps: step 1, names of plants which have been studied as sleep aids in humans were searched and retrieved; and step 2, each ingredient listed in step 1 was then added into the search term. Only original articles or reviews were applicable to the scope of this review. Studies on human subjects, with or without sleep-related disorders, were included. Sleep-related disorders refer to not only insomnia or sleep behavior disorders but also diseases with sleep-related symptoms. Studies were considered eligible for this review when the plant extracts were administered orally. Outcome measures relevant to sleep quality, duration, or other sleep-related problems were included. Twenty-one plants were listed in the first step of the search as potential candidates for natural sleep aids. Seventy-nine articles using these single plant-derived natural products were included in the final review. Although valerian was most frequently studied, conflicting results were reported, possibly due to the various outcome measures of each study. Other plants were not as rigorously tested in human studies. There was limited evidence with inconclusive results regarding the effects of single plant-derived natural products on sleep, warranting further studies.

Topics: Animals; Disease Models, Animal; Humans; Hypericum; Kava; Lavandula; Non-Randomized Controlled Trials as Topic; Observational Studies as Topic; Plant Extracts; Plant Preparations; Randomized Controlled Trials as Topic; Sleep; Sleep Initiation and Maintenance Disorders; Valerian

Hypericum perforatum (Hp) extracts contain many different classes of constituents including flavonoids and biflavonoids, phloroglucinols, naphthodianthrones, caffeic acid derivatives, and unknown and/or unidentified compounds. Many constituents may be responsible for the anti-inflammatory activity of Hp including quercetin and derivatives, hyperforin, pseudohypericin, and amentoflavone. In line with antidepressant data, it appears that the interactions of constituents may be important for the anti-inflammatory activity of Hp. Interactions of constituents, tested in bioavailability models, may explain why synergistic mechanisms have been found to be important for antidepressant and antiproliferative bioactivities. This review highlights the relationship among individual constituents and the anti-inflammatory activity of Hp extracts and proposes that interactions of constituents may be important for the anti-inflammatory activity of botanical extracts, although the exact mechanisms of the interactions are still unclear.

Topics: Animals; Anti-Inflammatory Agents; Biflavonoids; Disease Models, Animal; Flavonoids; Humans; Hypericum; Perylene; Phloroglucinol; Plant Extracts; Signal Transduction; Terpenes

St. John's wort (Hypericum perforatum L., SJW) contains numerous compounds with documented biological activity. Constituents that have stimulated the most interest include the naphthodianthrones hypericin and pseudohypericin, a broad range of flavonoids, and the phloroglucinols hyperforin and adhyperforin. According to the actual state of scientific knowledge the total extract has to be considered as the active substance. Although there are some open questions, the bulk of data suggests that several groups of active compounds are contributing to the antidepressant efficacy of the plant extract.

Topics: Animals; Anthracenes; Antidepressive Agents; Bridged Bicyclo Compounds; Cells, Cultured; Clinical Trials as Topic; Disease Models, Animal; Humans; Hypericum; Ice; Meta-Analysis as Topic; Perylene; Phloroglucinol; Phytotherapy; Plant Extracts; Terpenes

Clinical data indicate that hydroalcoholic extracts of Hypericum perforatum might be as valuable as conventional antidepressants in mild-to-moderate depression, with fewer side effects. One clinical trial using two extracts with different hyperforin contents indicated it as the main active principle responsible for the antidepressant activity. Behavioural models in rodents confirm the antidepressant-like effect of Hypericum extracts and also of pure hyperforin and hypericin. A hydroalcoholic extract lacking hyperforin also lacks the antidepressant-like effect. According to pharmacokinetic data and binding studies, it appears that the antidepressant effect of Hypericum extract is unlikely be due to an interaction of hypericin with central neurotransmitter receptors. The main in vitro effects of hyperforin (at concentrations of 0.1-1 microM) are non-specific presynaptic effects, resulting in the non-selective inhibition of the uptake of many neurotransmitters, and the interaction with dopamine D1 and opioid receptors. However, it is still not clear whether these mechanisms can be activated in vivo, since after administration of Hypericum extract brain concentrations of hyperforin are well below those active in vitro. In the rat, Hypericum extract might indirectly activate sigma receptors in vivo (through the formation of an unknown metabolite or production of an endogenous ligand), suggesting a new target for its antidepressant effects.

Topics: Animals; Anthracenes; Bridged Bicyclo Compounds; Depression; Disease Models, Animal; Hypericum; Neurotransmitter Agents; Perylene; Phloroglucinol; Phytotherapy; Plant Extracts; Rats; Receptors, Dopamine D1; Receptors, Opioid; Terpenes

The phloroglucinol derivative hyperforin has been recently shown to be a major antidepressant component in the extract of Hypericum perforatum. Experimental studies clearly demonstrated its activity in different behavioral models of depression. Moreover clinical studies linked the therapeutic efficacy of Hypericum extracts to their hyperforin content, in a dose-dependent manner. The molecular mechanism of action of hyperforin is still under investigation. Hyperforin has been shown to inhibit, like conventional antidepressants, the neuronal uptake of serotonin, norepinephrine and dopamine. However, hyperforin inhibits also the uptake of gamma-aminobutyric acid (GABA) and L-glutamate. The uptake inhibition by hyperforin does not involve specific binding sites at the transporter molecules; its mechanism of action seems to be related to sodium conductive pathways, leading to an elevation in intracellular Na(+) concentration. Other additional mechanisms of action of hyperforin, involving ionic conductances as well synaptosomal and vesicular function, have been suggested. In addition to its antidepressant activity, hyperforin has many other pharmacological effects in vivo (anxiolytic-like, cognition-enhancing effects) and in vitro (antioxidant, anticyclooxygenase-1, and anticarcinogenic effects). These effects could be of clinical importance. On the other hand, the role of hyperforin in the pharmacological interactions occurring during Hypericum extract therapy must be fully investigated. Hyperforin seems to be responsible for the induction of liver cytochrome oxidase enzymes and intestinal P-glycoprotein. Several pharmacokinetic studies performed in rats and humans demonstrated oral bioavailability of hyperforin from Hypericum extract. Only recently a new chromatographic method for detection of hyperforin in the brain tissue has been developed and validated. Taking into account the chemical instability of hyperforin, current efforts are directed to the synthesis of new neuroactive derivatives.

Topics: Animals; Antidepressive Agents; Bridged Bicyclo Compounds; Clinical Trials as Topic; Depression; Disease Models, Animal; Drug Interactions; Humans; Hypericum; Phloroglucinol; Terpenes

Sigma (sigma) receptors, first defined as a subclass of opioid receptors, later confounded with the high affinity phencyclidine (PCP) binding sites, now are regarded as unique binding sites, distinct from opiate and PCP receptors, and related to higher brain function. The investigation of functional significance of sigma receptors in the brain has been hampered for many years by relative lack of specific tool drugs and by the unavailability of their coherent classification into postulated agonists and antagonists. However, a potential involvement of sigma receptors in psychotic disorders was first suggested soon after their discovery. The sigma receptors are classified into two subtypes, sigma (1) and sigma (2) receptors, of which the first was recently cloned from rodent and human tissues while the second has not yet been fully characterized. Although the precise mechanism of the functional response of these receptors is still uncertain, it is accepted that sigma receptors can modulate a number of central neurotransmitter systems, including noradrenergic, glutamatergic and dopaminergic ones. The sigma receptors have been postulated to be involved in numerous pharmacological and physiological functions, including motor disorders, psychotic disorders, neuroprotective mechanisms. In the last years, a number of compounds with a high affinity and selectivity for sigma binding sites have been discovered and investigated for their therapeutic potential. In this review, we try to summarize the behavioral effects of sigma receptor ligands that have been described, and their activity in animal models related to some brain disorders, especially schizophrenia and affective disorders.

Topics: Amnesia; Animals; Antidepressive Agents; Cinnamates; Cocaine-Related Disorders; Cyclopropanes; Disease Models, Animal; Drug Interactions; Humans; Hypericum; Ligands; Nootropic Agents; Piperazines; Plant Extracts; Psychopharmacology; Psychotic Disorders; Quinolones; Receptors, sigma; Steroids

Extracts of Hypericum perforatum L. (St John's wort) are now successfully competing for status as a standard antidepressant therapy. Because of this, great effort has been devoted to identifying the active antidepressant compounds in the extract. From a phytochemical point of view, St John's wort is one of the best-investigated medicinal plants. A series of bioactive compounds has been detected in the crude material, namely flavonol derivatives, biflavones, proanthocyanidines, xanthones, phloroglucinols and naphthodianthrones. Although St John's wort has been subjected to extensive scientific studies in the last decade, there are still many open questions about its pharmacology and mechanism of action. Initial biochemical studies reported that St John's wort is only a weak inhibitor of monoamine oxidase-A and -B activity but that it inhibits the synaptosomal uptake of serotonin, dopamine and noradrenaline (norepinephrine) with approximately equal affinity. However, other in vitro binding assays carried out using St John's wort extract demonstrated significant affinity for adenosine, GABA(A), GABA(B) and glutamate receptors. In vivo St John's wort extract leads to a downregulation of beta-adrenergic receptors and an upregulation of serotonin 5-HT(2) receptors in the rat frontal cortex and causes changes in neurotransmitter concentrations in brain areas that are implicated in depression. In studies using the rat forced swimming test, an animal model of depression, St John's wort extracts induced a significant reduction of immobility. In other experimental models of depression, including acute and chronic forms of escape deficit induced by stressors, St John's wort extract was shown to protect rats from the consequences of unavoidable stress. Recent neuroendocrine studies suggest that St John's wort is involved in the regulation of genes that control hypothalamic-pituitary-adrenal axis function. With regard to the antidepressant effects of St John's wort extract, many of the pharmacological activities appear to be attributable to the naphthodianthrone hypericin, the phloroglucinol derivative hyperforin and several flavonoids. This review integrates new findings of possible mechanisms that may underlie the antidepressant action of St John's wort and its active constituents with a large body of existing literature.

Topics: Animals; Antidepressive Agents; Behavioral Medicine; Biogenic Monoamines; Depression; Disease Models, Animal; Humans; Hypericum; Phytotherapy; Plant Extracts; Receptors, Neurotransmitter

The present paper briefly reviews the most relevant experimental data on the reducing effect of some medicinal herbs on voluntary alcohol intake in animal models of alcoholism. Pueraria lobata, Tabernanthe iboga, Panax ginseng, Salvia miltiorrhiza and Hypericum perforatum proved to be effective in decreasing alcohol consumption. Reduction of alcohol absorption from the gastrointestinal system appears to be a common feature among most of the above plants. These data suggest that medicinal plants may constitute novel and effective pharmacotherapies for alcoholism.

Topics: Alcoholism; Animals; Antidepressive Agents; Disease Models, Animal; Humans; Hypericum; Panax; Phytotherapy; Plant Extracts; Plant Roots; Plants, Medicinal; Pueraria; Rats; Salvia; Tabernaemontana

The consequences of increased industrialization increased the risk of asthma and breathing difficulties due to increased particulate matter in the air. We aim to investigate the therapeutic properties of Hypericum ascyron L. extract (HAE) in airway inflammation and unravel its mechanism of action. We conducted nitric oxide and cell viability assay, real-time PCR and western blot analyses along with in vitro studies. in vivo studies include a model of coal fly ash and diesel exhaust particle (CFD)-induced airway inflammation in mice. HAE reduced coal fly ash (CFA)-induced nitric oxide secretion without exhibiting cytotoxicity in MH-S cells. HAE also reduced the mRNA expression of pro-inflammatory cytokines and reduced the expression of proteins in the NFκB and MAPK pathways. In a mice model of CFD-induced airway inflammation, HAE effectively reduced neutrophil infiltration in bronchoalveolar lavage fluid (BALF) and increased the amount of T cells in the BALF, lungs, and blood while reducing all other immune cell subtypes to reduce airway inflammatory response. CXCL-1, IL-17, MIP-2, and TNF-α expression in the BALF were also reduced. HAE effectively reduced MIP-2 and TNF-α mRNA expression in the lung tissue of mice. In a nutshell, HAE is effective in preventing airway inflammation induced by CFA in MH-S cells, as well as inflammation induced by CFD in mice.

Topics: Animals; Disease Models, Animal; Hypericum; Inflammation; Mice; Particulate Matter

Hypericum perforatum L. (HP), a well-known natural medicine, has a potential effect on menopausal hypercholesterolemia. However, the effect of HP extract on gut microbiota and related metabolites, which play vital roles in metabolic disease occurrence, in the context of estrogen deficiency have not yet been reported. The aims of the present study were to investigate the effects of HP extract on gut microbial composition and related metabolite profiles in ovariectomized (OVX) rats and reveal the relationships between pathological indicators and alterations in both gut microbial composition at the genus level and metabolites. Body weight, serum parameters, liver lipids and histomorphology were determined. Microbial composition was analyzed using 16S rRNA sequencing. Fecal short-chain fatty acids (SCFAs) and serum bile acids were quantitatively measured. Correlations between pathological indicators and alteration in gut microbiota and metabolites were investigated using Spearman's rank correlation test. Gene expression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7α-hydroxylase (CYP7A1) and cholesterol 27-hydroxylase (CYP27A1) in the liver and G protein-coupled receptors (GPCRs; GPR43 and GPR41), ZO-1 and occludin in the cecum were determined by PCR. Microbial composition and metabolite profiles were significantly changed in OVX rats compared with sham rats. Twelve bacterial genera, 5 SCFAs and 12 bile acids were identified as differential biomarkers. Differential genera, SCFAs and bile acids were closely associated with weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). In OVX rats, HP administration can significantly reverse the pathological symptoms of body weight gain, serum lipid disorders and hepatic steatosis, at the meanwhile, reestablish gut microbial composition and metabolite profiles. Moreover, HP administration significantly upregulated the levels of CYP7A1, GPR43 and GPR41. In conclusion, HP can ameliorate estrogen deficiency-induced hypercholesterolemia. The underlying mechanism may be associated with improvements in gut microbiota composition and the profile of related metabolites as well as increases in bile acid secretion.

Topics: Animals; Anticholesteremic Agents; Bacteria; Bile Acids and Salts; Biomarkers; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Disease Models, Animal; Down-Regulation; Estrogens; Female; Gastrointestinal Microbiome; Hypercholesterolemia; Hypericum; Intestines; Liver; Ovariectomy; Plant Extracts; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled

BACKGROUND This network pharmacology study aimed to identify the active compounds and molecular mechanisms involved in the effects of Hypericum japonicum on cholestatic hepatitis. We validated the findings in an alpha-naphthylisothiocyanate (ANIT) rat model of hepatotoxicity. MATERIAL AND METHODS The chemical constituents and targets of H. japonicum and target genes previously associated with cholestatic hepatitis were retrieved from public databases. A network was constructed using Cytoscape 3.7.2 software and the STRING database and potential protein functions were analyzed based on the public platform of bioinformatics. ANIT was used to induce cholestatic hepatitis in a rat model using 36 Sprague-Dawley rats, and this model was used to investigate intervention with 3 doses of quercetin (low-dose, 50 mg/kg; medium-dose, 100 mg/kg; and high-dose, 200 mg/kg), the main active component of H. japonicum. Levels of serum biochemical indexes were measured by commercial kits, and the messenger RNA (mRNA) levels of markers of liver and mitochondrial function and oxidative stress were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS The main active ingredients of H. japonicum were quercetin, kaempferol, and tetramethoxyluteolin, and their key targets included prostaglandin G/H synthase 2 (PTGS2), B-cell lymphoma-2 (BCL2), cholesterol 7-alpha hydroxylase (CYP7A1), and farnesoid X receptor (FXR). Quercetin intervention promoted recovery from cholestatic hepatitis. CONCLUSIONS The findings from this research provide support for future research on the roles of quercetin, kaempferol, and tetramethoxyluteolin in human liver disease and the roles of the PTGS2, BCL2, CYP7A1, and FXR genes in cholestatic hepatitis.

Topics: 1-Naphthylisothiocyanate; Animals; Chemical and Drug Induced Liver Injury; Cholangitis; Cholestasis; Disease Models, Animal; Hepatitis; Hepatocytes; Hypericum; Kaempferols; Liver; Liver Diseases; Luteolin; Male; Oxidative Stress; Plant Extracts; Quercetin; Rats; Rats, Sprague-Dawley

The genus Hypericum are widely distributed in China. Hypericum perforatum L. (genus Hypericum, family Hypericaceae) has a long history as a traditional Chinese medicine, which was traditionally used for the treatment of emotional distress, cardiothoracic depression, and acute mastitis. Hyperoside (Hyp) extracted from Hypericum perforatum L. has been affirmed to exert therapeutic effects on cardiovascular diseases, with widespread existence in plants of genus Hypericum. Hyp could also be extracted from Crataegus pinnatifida Bunge (genus Crataegus pinnatifida Bunge, family Rosaceae), another traditional Chinese medicine that traditionally prevented and treated heart disease in China. The cardioprotection and mechanism of Hyp comprise anti-inflammation, anti-fibrosis, activation of autophagy, and reversal of cardiac remodeling.. This study aimed to explore the Hyp effect against MI and its underlying mechanism.. The MI model was constructed in the KM mice via a ligating surgery of the left anterior descending (LAD) coronary artery. Subsequently, the mice were divided into following seven groups: Sham group, MI group, MI + Hyp 9 mg/kg group, MI + Hyp18 mg/kg group, MI + Hyp36 mg/kg group, MI + Fosinopril group, and MI + Hyp-36 mg/kg+3-MA group. Each group was treated with Hyp in different concentrations or positive medicine for two weeks except for the sham group. After two weeks, we examined the cardiac function, electrocardiogram (ECG), myocardial hypertrophy in the non-infarct area, collagen volume fraction (CVF), perivascular collagen area (PVCA) in the infarct area, and several serum cytokines. Autophagy and inflammation in cardiomyocytes were assessed via measuring autophagy-associated proteins and NLRP1 inflammasome pathway related proteins.. Hyp reversed LV remodeling and adverse ECG changes through reducing CVF and myocardial hypertrophy. Additionally, Hyp treatment could reduce inflammation levels in cardiomyocytes, compared with those in MI group. Moreover, NLRP1inflammation pathway was activated after MI. Up-regulation of autophagic flux suppressed NLRP1 inflammation pathway after Hyp treatment. However, co-treatment with 3-MA abrogated above effects of Hyp.. Hyp had obvious protective effect on heart injury in MI mice. Echocanrdiographic and histological measurements demonstrated that Hyp treatment improved cardiac function, and ameliorated myocardial hypertrophy and fibrinogen deposition after MI. The partial mechanism is that Hyp could up-regulate autophagy after MI. Furthermore, the promotion of autophagic flux would suppress NLRP1 inflammation pathway induced by MI.

Topics: Adaptor Proteins, Signal Transducing; Animals; Apoptosis Regulatory Proteins; Autophagy; Body Weight; Cardiotonic Agents; Cytokines; Disease Models, Animal; Electrocardiography; Heart Diseases; Hypericum; Inflammation; Male; Medicine, Chinese Traditional; Myocardial Infarction; Myocytes, Cardiac; Organ Size; Quercetin; Signal Transduction; Ventricular Remodeling

High-fat diet (HFD) can induce deficits in neural function, oxidative stress, and decrease hippocampal neurogenesis. Hypericum (H.) scabrum extract (Ext) contains compounds that could treat neurological disorders. This study aimed to examine the neuroprotective impacts of the H. scabrum Ext on hippocampal synaptic plasticity in rats that were fed HFD. Fifty-four male Wistar rats (220 ± 10 g) were randomly arranged in six groups: (1) HFD group; (2) HFD + Ext300 group; (3) HFD + Ext100 group; (4) Control group; (5) Ext 300 mg/kg group; (6) Ext 100 mg/kg group. These protocols were administrated for 3 months. After this stage, a stimulating electrode was implanted in the perforant pathway (PP), and a bipolar recording electrode was embedded into the dentate gyrus (DG). Long-term potentiation (LTP) was provoked by high-frequency stimulation (HFS) of the PP. Field excitatory postsynaptic potentials (EPSP) and population spikes (PS) were recorded at 5, 30, and 60 min after HFS. The HFD group exhibited a large and significant decrease in their PS amplitude and EPSP slope as compared to the control and extract groups. In reverse, H. scabrum administration in the HFD + Ext rats reversed the effect of HFD on the PS amplitude and EPSP slope. The results of the study support that H. scabrum Ext can inhibit diminished synaptic plasticity caused by the HFD. These effects are probably due to the extreme antioxidant impacts of the Ext and its capability to scavenge free radicals.

Topics: Animals; Antioxidants; Brain; Dentate Gyrus; Diet, High-Fat; Disease Models, Animal; Hippocampus; Hypericum; Long-Term Potentiation; Male; Neuronal Plasticity; Plant Extracts; Rats; Rats, Wistar

The most frequent etiologic cause is alkaline substances. We investigated the protective effects of the plant St. John 's Wort (Hypericum perforatum).. We included 42 Wistar albino rats weighing between 200-300 grams and divided into six groups as Group 1: Control, Group 2: Burn+Saline (BS), Group 3: Burn+St. John's Wort (BSJW), Group 4: Burn+Plasebo (BP), Group 5: St. John's Wort (SJW), Group 6: Placebo (P). After 15 days of treatment, esophagus, stomach and liver tissue samples were derived by dissection for histopathologic and biochemical markers. The cytotoxic effects of formulation on fibroblasts is evaluated in vitro on human dermoblast fibroblast line (HDFa, Gibco Invitrogen cell culture, C-013-5C).. The weight of the rats increased in Group 1, 3, 4, 6, decreased in Group 2 and did not change in Group 5. In the BSJW group, submucosal collagen accumulation, muscularis mucosa damage, tunica muscularis damage and collagen accumulation in esophagus were similar to the control group but lesser than BS and placebo group. In the stomach, mucosal damage, gastric gland dilatation, submucosal polymorphonuclear infiltration were similar to the control group and lesser than the BS group. The lethal concentration of SJW was 2.58 gr/mL.. SJW substrate is effective in protecting the esophagus and stomach in mild to moderate alcali corrosive burns in the subacute period. We should keep in mind the protective effects of STW substrate in alkaline corrosive burns of the gastrointestinal system.

Topics: Animals; Burns, Chemical; Caustics; Cell Line; Cell Survival; Disease Models, Animal; Fibroblasts; Humans; Hypericum; Plant Extracts; Rats; Upper Gastrointestinal Tract

Posttraumatic stress disorder (PTSD) is a serious mental health condition that affects some individuals who have witnessed or experienced a life-threatening or traumatic event. An enhanced or exaggerated acoustic startle response (ASR), reflecting heightened sensitivity to unexpected, loud sound, is a hallmark symptom of PTSD. Antidepressant medications, such as sertraline, are first-line pharmacotherapeutic agents in the treatment of PTSD, but concerns about potential side effects or taking synthetic drugs prompt discovery of naturalistic therapeutic agents. This study examined the relative effectiveness of a compound containing St. John's Wort (SJW), an herb widely prescribed for depression in Europe and sold as a dietary supplement in the United States, compared to sertraline (Zoloft) in a mouse model of PTSD. Thirty-six mice were tested for baseline ASR, then they were exposed to rats in a predator exposure paradigm known to induce PTSD-like symptoms. Mice were randomly divided into three groups for treatment (control, sertraline, SJW), and ASR was retested one week later. One-way ANOVAs found no significant group differences in ASR amplitude at baseline but a significant effect of Treatment Group after predator exposure,

Topics: Animals; Disease Models, Animal; Hypericum; Mice; Mice, Inbred C57BL; Phytotherapy; Plant Extracts; Reflex, Startle; Selective Serotonin Reuptake Inhibitors; Sertraline; Stress Disorders, Post-Traumatic

This study was conducted to explore whether Hypericum perforatum L. (HPL) as a potent antioxidant protects against oxidative stress, cytokine production and caspase expression in muscle (soleus), brain and blood of sciatic nerve injury (SNI)-induced rats.. Thirty-five rats were equally divided into five groups. The first and second were used as untreated control and sham control groups, respectively. The third, fourth and fifth were sham + HPL, SNI and SNI + HPL groups, respectively. The third and fifth groups received 30 mg/kg HPL via gastric gavage for 28 days.. High levels of muscle, brain and red blood cell (RBC) lipid peroxidation, plasma cytokine (TNF-α, IL-1β and IL-2), muscle PARP, caspase 3 and 9 expression levels were decreased by HPL treatments. Plasma glutathione peroxidase (GPx) activity, α-tocopherol and melatonin, muscle, brain and RBC reduced glutathione (GSH) concentrations were decreased by SNI induction, whereas their values were increased by HPL treatments. β-carotene and retinol concentrations did not change in the five groups.. HPL may play a role in preventing SNI-induced inflammatory, oxidative and apoptotic blood, muscle and brain damages through upregulation of the GSH and GPx values but downregulation of PARP, caspase level and cytokine production in SNI-induced rats.

Topics: Animals; Antioxidants; Apoptosis; Brain; Cytokines; Disease Models, Animal; Female; Hypericum; Inflammation; Lipid Peroxidation; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Sciatic Nerve

We investigated the effects of Oenothera biennis L. and Hypericum perforatum L. extracts on brain tissue histopathology, myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) in mice with experimental autoimmune encephalomyelitis (EAE). Forty-seven C57BL/6J mice were divided into the following groups: multiple sclerosis (MS), control (healthy mice), MS + H. perforatum treated (MS + HP), MS + O. biennis treated (MS + OB). All groups except the control group were immunized by EAE methods. Two weeks after the immunization, the mice in the MS + HP group were fed normal food containing 18 - 21 g/kg H. perforatum extract, the mice in MS + OB group were fed normal food containing 18 - 21 g/kg O. biennis extract, and the mice in control and MS groups were fed normal food for six weeks. Brain tissue samples were collected from all mice for histopathological and biochemical analysis. Clinical signs of the disease were scored using functional systems scores (FSS) daily. The H. perforatum and O. biennis extracts ameliorated the increased brain tissue MOG and MBP values for animals with MS. H. perforatum and O. biennis extract decreased the TOS and OSI values for brain tissue and increased TAS levels in brain tissue of animals with MS. In addition, H. perforatum and O. biennis extracts decreased the clinical signs at the end of the experiment compared to the beginning of extract administration. We found that myelin was lost in MS group vs. control group. H. perforatum and O. biennis extract treatments decreased the amount of myelin loss in the MS + HP and MS + OB groups. We also observed amyloid deposition on vascular walls, in the cytoplasm of the neurons and in the intercellular space in the MS group. O. biennis and H. perforatum treated groups exhibited neither abnormal amyloid deposition nor obvious cell infiltration. The beneficial effects of O. biennis and H. perforatum for attenuating myelin loss and amyloid deposition suggest their therapeutic utility for treatment of MS.

Topics: Animals; Central Nervous System; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Hypericum; Mice, Inbred C57BL; Multiple Sclerosis; Myelin Sheath; Myelin-Oligodendrocyte Glycoprotein; Neurons; Oenothera biennis; Oxidative Stress

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.

Topics: Animals; Antidepressive Agents; Antioxidants; Chromatography, High Pressure Liquid; Depression; Disease Models, Animal; Fruit; Hindlimb Suspension; Hypericum; Male; Mice, Inbred BALB C; Plant Extracts; Stroke; Swimming; Water

Parkinson's Disease (PD) is a progressive neurodegenerative disorder, hallmark of which is loss of nigral dopaminergic neurons. Since a  Hypericum polyanthemum extract inhibits monoamine reuptake and some of its constituents present cytotoxic properties, the aim of this study was to evaluate the effect of this extract in an animal PD model.. Adult Wistar rats (110 days old) received 6-hydroxydopamine (6-OHDA) infusions into the right medial forebrain bundle. A cyclohexane extract from aerial parts of H. polyanthemum (POL; 90 mg/kg/administration; gavage) was administered in three different regimens. In Regimens 1 and 2, rats received 3 administrations of POL starting 4 or 24 h after 6-OHDA infusion, respectively. In Regimen 3, these administrations were carried out 1 day before any evaluation of ipsilateral rotational activity induced by methylphenidate (MP, 20 mg/kg, i.p.). MP was administered 10, 45, and 85 days after 6-OHDA infusion in all groups. Nigral tyrosine hydroxylase (TH) immunocontent was evaluated 120 days after 6-OHDA infusion in animals submitted to Regimen 2 only. The effect of POL on apomorphine-induced climbing behavior in non-lesioned adult CF1 mice (60 days old) treated with POL was also evaluated.. Regimen 2 increased MP-induced rotational activity and decreased nigral TH levels in 6-OHDA-lesioned rats. Rotational activity was not altered in regimens 1 and 3. In addition, no change in climbing behavior was observed in non-lesioned mice.. Together, these results indicate that, in 6-OHDA-lesioned rats, a cyclohexane  H. polyanthemum extract potentiates neurotoxicity and MP-induced motor asymmetry depending on the time of administration. In the short term, it seems to not act directly on mice dopaminergic receptors.

Topics: Animals; Behavior, Animal; Disease Models, Animal; Dopamine; Hydroxydopamines; Hypericum; Motor Activity; Neuroprotective Agents; Neurotoxicity Syndromes; Rats, Wistar; Substantia Nigra; Tyrosine 3-Monooxygenase

Alzheimer's disease (AD) is a progressive and ultimately fatal neurodegenerative diseases. Aluminum, a neurotoxic metal, is considered as the pathological hallmark and contributing factor of AD. Hypericum perforatum extract (HPE) is a neuroprotective agent that can prevent neurodegenerative pathologies through antioxidants, anti-inflammatory and regulating neurotransmitter release in animal model of neuropathy. The present study aimed to identify the potential neuroprotective of HPE on AlCl

Topics: Acetylcholinesterase; Aluminum Chloride; Aluminum Compounds; Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Chlorides; Disease Models, Animal; Glutathione; Hippocampus; Hypericum; Interleukin-1beta; Interleukin-6; Lipid Peroxidation; Male; Maze Learning; Neuroprotective Agents; Oxidative Stress; Plant Extracts; Plaque, Amyloid; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

In this study, we compared the efficacy of a combination of PKC-blocker St. John's Wort (SJW) and morphine in mice with painful antiretroviral (2,3-dideoxycitidine [ddC]) and chemotherapic (oxaliplatin) neuropathy.. Morphine (1 and 5 mg/Kg i.p.), SJW (1 and 5 mg/Kg o.s.), or their combination was administered by systemic injection, and antinociception was determined by using the hot and cold plate tests.. Here we demonstrate the ability of SJW to relieve neuropathic pain in mice neuropathic models and a potentiation of morphine antinociception in thermal pain. The potentiating effect shown by SJW was not secondary to its antinociceptive activity as the increase of the morphine antinociceptive effect was produced at a dose (1mg/kg o.s.) devoid of any capability to modulate the pain threshold in neuropathic pain mice. Further examinations of the SJW main components revealed that hypericin was responsible for the potentiating properties whereas flavonoids were ineffective.. These results show that SJW has notable antinociceptive activity for both neuropathic pain models and could be used in neuropathic pain relief alone or in combination with morphine. These data support the utility of combination SJW/opioid therapy in pain management for antinociceptive efficacy by enhancing opioid analgesia.

Topics: Animals; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Hypericum; Male; Mice; Morphine; Neuralgia; Pain Measurement; Plant Extracts; Reaction Time; Treatment Outcome

The aim of this study was to investigate the probable effects of Hypericum perforatum (HP) on wound healing in diabetic rats.. Thirty-five male Wistar rats were divided evenly into 5 groups. Diabetes formation was induced by intraperitoneal streptozotocin (60 mg/kg) administration for groups 1 (HP extract in olive oil), 2 (HP extract in ethanol), 3 (povidone-iodine application), and 4 (diabetic rats without any applied medication); group 5 was the control. Dorsal dermoepidermal incision was performed on each rat after 48 hours. The aforementioned solutions were applied only to groups 1, 2, and 3; groups 4 and 5 did not receive solution applications. At the end of the 7-day period, the cutaneous tissue was resected from the center of the incised and sutured region and divided into 3 pieces for biomechanical, biochemical, and histopathological assessments.. Ultimate stress and toughness significantly decreased in groups 3, 4, and 5 compared to group 1. There was a significant difference between groups 2 and 3 for the same parameters (P < .05). Compared with group 4, tissue malondialdehyde levels were found to be lower in the HP groups (P < .05). Histopathological evaluation revealed the fibroblast count was reduced considerably in the HP-applied rats compared with other groups (P < .05).. Application of HP may be recommended as effective on wound healing in diabetic rats, but further investigation is needed to adapt the findings for clinical use.

Topics: Administration, Cutaneous; Animals; Anti-Infective Agents, Local; Diabetes Mellitus, Experimental; Disease Models, Animal; Hypericum; Male; Olive Oil; Plant Extracts; Rats; Rats, Wistar; Wound Healing; Wounds and Injuries

Parkinson's disease is the second most common neurodegenerative disorder with selective and progressive decline of nigral dopaminergic neurons. Hypericum perforatum L. (H. perforatum, St. John's wort) has been traditionally used for management of different disorders, especially mild-to-moderate depression. This study was conducted to evaluate the effect of H. perforatum extract against unilateral striatal 6-hydroxydopamine (6-OHDA) toxicity and to unmask some involved mechanisms. Intrastriatal 6-OHDA-lesioned rats were treated with H. perforatum hydroalcoholic extract at a dose of 200 mg/kg/day started 1 week pre-surgery for 1 week post-surgery. The extract attenuated apomorphine-induced rotational behavior, decreased the latency to initiate and the total time on the narrow beam task, lowered striatal level of malondialdehyde and enhanced striatal catalase activity and reduced glutathione content, normalized striatal expression of glial fibrillary acidic protein, tumor necrosis factor α with no significant effect on mitogen-activated protein kinase, lowered nigral DNA fragmentation, and prevented damage of nigral dopaminergic neurons with a higher striatal tyrosine hydroxylase immunoreactivity. These findings reveal the beneficial effect of H. perforatum via attenuation of DNA fragmentation, astrogliosis, inflammation, and oxidative stress.

Topics: Animals; Apomorphine; Catalase; Corpus Striatum; Disease Models, Animal; Ethanol; Glutathione; Hypericum; Male; Malondialdehyde; Mitogen-Activated Protein Kinases; Motor Activity; Neuroprotective Agents; Oxidopamine; Parkinson Disease; Plant Extracts; Rats, Wistar; Reaction Time; Tumor Necrosis Factor-alpha; Tyrosine 3-Monooxygenase; Water

Multiple sclerosis (MS) is a central nervous system disorder mainly characterized by inflammation, demyelination and axonal injury. Anti-inflammatory agents can be used to ameliorate the disease process. Hypericum perforatum L or St. John's wort is widely used as an anti-depressant and anti-inflammatory remedy in traditional and herbal medicine. Based on St. John's wort properties, the therapeutic potentials of an H. perforatum extract (HPE) and a single component, hyperforin were evaluated for effectiveness against MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Female C57BL/6 mice were immunized with specific antigen MOG35-55 and then administered different doses of hyperforin or HPE post-immunization. Clinical symptoms/other relevant parameters were assessed daily. Histological analysis of the spinal cord was performed. T-cell proliferative activity was also evaluated using a BrdU assay. The effect of hyperforin on regulatory T-cells (Treg cells) was assessed using flow cytometry. The results indicate hyperforin and HPE reduced the incidence and severity of EAE, an outcome that closely correlated with an inhibition of pathological features (leukocyte infiltration and demyelination) and antigen-specific T-cell proliferation. The study also showed that hyperforin caused increased Treg cell levels in the spleen. These results indicated that hyperforin and HPE could attenuate EAE autoimmune responses by inhibiting immune cell infiltration and expansion of Treg cell and could eventually be considered as a potential candidate for use in the treatment of MS.

Topics: Animals; Cell Proliferation; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Humans; Hypericum; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Peptide Fragments; Phloroglucinol; Phytotherapy; Spleen; T-Lymphocytes, Regulatory; Terpenes

Context Hypericum perforatum L. (Hypericaceae), used in moderate depression treatment, is active in experimental tests for antidepressant activity. For H. connatum Lam., a South American species lacking hyperforin, antidepressant effects have not been demonstrated. Objective This study evaluates the antidepressant-like effect of H. connatum in rats and identifies the components involved in this activity. Materials and methods First, the effects of acute and 14-d oral administrations of an extract derived from H. connatum aerial parts were studied using the Escape Deficit (ED) test. Next, methanol-extracted flavonoid-enriched fractions B and C and fraction-purified flavonoids (quercetin, rutin and isoquercitrin) were evaluated in the ED test after acute administration. To rule out possible confounding effects of the flavonoids, we examined nociceptive threshold using the tail-flick test and anxious behaviour using the elevated plus maze (EPM) test. Results Hypericum connatum increased reactivity of unavoidable stress-exposed rats after acute (0.5 and 1 g/kg: ED = 18.6/30 and 19.8/30, respectively) and repeated administration (0.5 g/kg twice daily: ED = 17.8/30). Protective effects were observed for fractions B and C (250 mg/kg: ED = 18.1/30 and 18.8/30, respectively), quercetin (2.5, 5 and 10 mg/kg: ED = 15.3/30, 18.3/30 and 21.6/30, respectively), rutin (5 and 10 mg/kg: ED = 15.4/30 and 13.0/30, respectively) and isoquercitrin (2.5 mg/kg: ED = 19.2/30). The flavonoids did not modify nociceptive threshold or performance in the EPM test. Discussion and conclusion Hypericum connatum showed protective activity in the ED test, a correlate of potential antidepressant-like effects that appeared to be related to the flavonoid components of this species.

Topics: Administration, Oral; Animals; Antidepressive Agents; Behavior, Animal; Depression; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Escape Reaction; Flavonoids; Hypericum; Locomotion; Male; Maze Learning; Nociception; Pain Threshold; Phytotherapy; Plant Components, Aerial; Plant Extracts; Plants, Medicinal; Quercetin; Rats, Sprague-Dawley; Rutin; Stress, Psychological

Our aim was to investigate the curative role of topical Hypericum perforatum (HP) in a rat model of tympanic membrane perforation in a histopathological manner.. This study was conducted on 30 female Sprague-Dawley rats. An HP extract was prepared as a suspension in pure olive oil. In all rats, the right and left tympanic membranes were perforated by a fine puncture under a microscope. Rats were randomly assigned to three groups. The HP extract was given as drops on a daily basis in Group 1, while olive oil alone was given on a daily basis in Group 2. In Group 3, the rats were allowed spontaneous recovery without any intervention. Three rats from each group were sacrificed on days 7, 14, and 21. Temporal bullae were removed for histopathological examination to evaluate fibroblast proliferation, leukocyte infiltration, neovascularization, and subepithelial thickness and to compare these among the groups.. In histopathological examination of the rats from each group on days 7, 14, and 21, there were significant differences in leukocyte infiltration, fibroblast proliferation, and subepithelial thickness. No significant difference was observed in neovascularization among the groups.. Compared with the spontaneous recovery group, HP was found to be more effective in a wound-healing model of the tympanic membrane. HP may be applied in clinical practice if it is shown to be safe with regard to ototoxicity.

Topics: Animals; Disease Models, Animal; Female; Hypericum; Phytotherapy; Rats; Rats, Sprague-Dawley; Tympanic Membrane Perforation; Wound Healing

Stress, via corticosteroids release, influences bone mass density. Hypericum perforatum (Hp) a traditional remedy possess antidepressive activity (serotonin reuptake inhibitor) and wound healing properties. Hp preparation contains mainly hypericin, hyperforin, hyperoside and flavonoids exerting oestrogen-mimetic effect. Cold swimming represents an experimental model of stress associating mental strain and corporal exhaustion.. This study investigates the Hp effect on femur and mandible bone mass changes in rats under cold forced swimming procedure.. 30 male Wistar rats were randomized into three groups. Group A was treated with Methanolic extract of Hp (Jarsin®) via gastroesophageal catheter, and was submitted to cold swimming stress for 10 min/daily. Group B was submitted to cold stress, since group C served as control. Experiment duration was 10 days. Haematocrite and serum free fatty acids (FFA) were estimated. Furthermore volume and specific weight of each bone as well as bone mass density via dual energy X-Ray absorptiometry (DEXA) were measured. Statistic analysis by t-test.. Hp treatment restores the stress injuries. Adrenals and bone mass density regain their normal values.. Injuries occurring by forced swimming stress in the rats are significantly improved by Hp treatment. Estrogen-like effects of Hp flavonoids eventually may act favorable in bone remodeling.

Topics: Animals; Bone Density; Cold Temperature; Disease Models, Animal; Femur; Hypericum; Male; Mandible; Phytotherapy; Plant Extracts; Random Allocation; Rats, Wistar; Stress, Psychological; Swimming

Sea buckthorn (Hippophae rhamnoides L.) and St. John's wort (Hypericum perforatum L.) are used as an emmenagog and for the treatment of other gynecological disorders including uterus inflammation and endometriosis. The aim of the present study is to investigate the potential of a mixture of sea buckthorn and St. John's wort oils (HrHp oil) in the treatment of endometriosis.. The activity was assessed in surgically induced endometriosis in rats. A 15-mm piece of endometrium was sutured into the abdominal wall. Twenty-eight days later, a second laparotomy was performed to calculate the endometrial foci areas and to score intra-abdominal adhesions. The rats were treated with either vehicle, HrHp oil formulation, or the reference (buserelin acetate). At the end of the experiment all rats were sacrificed and endometriotic foci areas and intra-abdominal adhesions were re-evaluated. The tissue sections were analyzed histopathologically. Peritoneal fluids of the experimental animals were collected in order to detect the levels of tumor necrosis factor-α, vascular endothelial growth factor, and interleukin-6, which might be involved in the etiology of endometriosis.. HrHp oil may be a promising alternative for the treatment of endometriosis.

Topics: Animals; Complementary Therapies; Disease Models, Animal; Drug Combinations; Endometriosis; Endometrium; Female; Hippophae; Humans; Hypericum; Interleukin-6; Plant Extracts; Plant Oils; Random Allocation; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factors; Vascular Endothelial Growth Factor A

Despite widespread use as well as epidemiologic indications, there have been no investigations into the effect of St. John's wort (SJW) extract on colorectal carcinogenesis in vivo. This study reports a systematic evaluation of the impact of dietary supplementation of SJW extract on azoxymethane-induced colorectal carcinogenesis in mice. Mice were fed with either AIN-93G (control) diet or SJW extract-supplemented diet (SJW diet) prior to azoxymethane treatment. SJW diet was found to significantly improve the overall survival of azoxymethane-treated mice. Pretreatment with the SJW diet significantly reduced body weight loss as well as decrease of serum albumin and cholesterol levels associated with azoxymethane-induced colorectal tumorigenesis. SJW diet-fed mice showed a significant decrease in tumor multiplicity along with a decrease in incidence of large tumors and a trend toward decreased total tumor volume in a dose-dependent manner. A short-term study, which examined the effect of SJW prior to rectal bleeding, also showed decrease in colorectal polyps in SJW diet-fed mice. Nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase (ERK1/2) pathways were attenuated by SJW administration. SJW extract resulted in early and continuous attenuation of these pathways in the colon epithelium of SJW diet-fed mice under both short-term and long-term treatment regimens. In conclusion, this study demonstrated the chemopreventive potential of SJW extract against colorectal cancer through attenuation of proinflammatory processes.

Topics: Animals; Anticarcinogenic Agents; Azoxymethane; Carcinogenesis; Cell Transformation, Neoplastic; Colon; Colorectal Neoplasms; Diet; Dietary Supplements; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Hypericum; Inflammation; Male; Mice; NF-kappa B; Oligonucleotide Array Sequence Analysis; Oligonucleotides; Plant Extracts; Signal Transduction

Tetrahydrohyperforin (IDN-5706) is a semisynthetic derivative of hyperforin, one of the main active components of Hypericum perforatum extracts. It showed remarkable positive effects on memory and cognitive performances in wild-type mice and in a transgenic mouse model of Alzheimer's disease, but little was known about the concentrations it can reach in the brain. The investigations reported herein show that repeated treatment of mice with tetrahydrohyperforin (20 mg/kg intraperitoneally, twice daily for 4 days and once on the fifth day) results in measurable concentrations in the brain, up to 367 ng/g brain (∼700 nM) 6 h after the last dose; these concentrations have significant effects on synaptic function in hippocampal slices. The other main finding was the identification and semiquantitative analysis of tetrahydrohyperforin metabolites. In plasma, three hydroxylated/dehydrogenated metabolites were the largest (M1-3) and were also formed in vitro on incubation of tetrahydrohyperforin with mouse liver microsomes; the fourth metabolite in abundance was a hydroxylated/deisopropylated derivative (M13), which was not predicted in vitro. These metabolites were all detected in the brain, with peak areas from 10% (M1) to ∼1.5% (M2, M3, and M13) of the parent compound. In summary, repeated treatment of mice with tetrahydrohyperforin gave brain concentrations that might well underlie its central pharmacological effects. We also provide the first metabolic profile of this compound.

Topics: Alzheimer Disease; Animals; Brain; Chromatography, High Pressure Liquid; Disease Models, Animal; Hippocampus; Hypericum; Mice; Microsomes, Liver; Molecular Structure; Phloroglucinol; Terpenes

Hypericum perforatum (HP) (St. John's Wort-Kantaron) has been used widely for the treatment of burn injuries for many years in traditional Turkish medicine. The aim of study was to investigate HP treatment in experimental thermal burns and compare it with silver sulfadiazine (SS) treatment.. Thirty-five rats were randomly assigned to one of the five groups, 7 rats in each. A second-degree thermal burn was created on the dorsal sites of rats by exposing an area of 4×4 cm to 100 °C boiled water for 10 seconds. All groups were provided with irrigation for three (3) minutes with 50 cc saline solution (SS). Group 1 (Control Group) was not administered any treatment. Group 2 (Burn Control Group) was administered only irrigation, Group 3 (topical silver sulfadiazine [SS]) was administered SS twice a day, Group 4 (the Topical HP Group) was administered HP four times a day (every six hours), Group 5 (treatment with agent -gel-) was administered other topical material used for the preparation of HP four times a day (every six hours). Wound site healing on the skin was histopathologically evaluated.. It was found that collagen discoloration of the HP treatment group was localized in the lower part of the epidermal layer and did not go up to the depth of dermis compared to the other groups, and epidermis, hair follicles and sebaceous glands remained protected compared to the groups administered burn, gel and SS in every hour of the experiment and it was the group closest to the control group structurally. It was determined that the epidermal thickness and the number of vessels of the HP Group were significantly higher compared to the other groups (p<0.05), which was the group closest to the control group in terms of these parameters and these numbers did not show any difference within hours (p>0.05). The number of degenerated hair follicles in the HP Group was significantly less than the other groups (p <0.05), and it was determined that the total number of hair follicles significantly increased in the twenty-fourth (p<0.05) and this number did not differ by the control group (p>0.05).. Administration of HP four times a day within the first 24 hours is clearly effective in wound healing in the experimental thermal second degree burn modality and is significantly superior to SS treatment.

Topics: Administration, Cutaneous; Animals; Anti-Infective Agents, Local; Burns; Disease Models, Animal; Female; Hypericum; Phytotherapy; Plant Extracts; Random Allocation; Rats; Rats, Wistar; Silver Sulfadiazine; Wound Healing

The adenosine triphosphate-binding cassette transport protein P-glycoprotein (ABCB1) is involved in the export of beta-amyloid from the brain into the blood, and there is evidence that age-associated deficits in cerebral P-glycoprotein content may be involved in Alzheimer's disease pathogenesis. P-glycoprotein function and expression can be pharmacologically induced by a variety of compounds including extracts of Hypericum perforatum (St. John's Wort). To clarify the effect of St. John's Wort on the accumulation of beta-amyloid and P-glycoprotein expression in the brain, St. John's Wort extract (final hyperforin concentration 5%) was fed to 30-day-old male C57BL/6J-APP/PS1(+/-) mice over a period of 60 or 120 days, respectively. Age-matched male C57BL/6J-APP/PS1(+/-) mice receiving a St. John's Wort-free diet served as controls. Mice receiving St. John's Wort extract showed (i) significant reductions of parenchymal beta-amyloid 1-40 and 1-42 accumulation; and (ii) moderate, but statistically significant increases in cerebrovascular P-glycoprotein expression. Thus, the induction of cerebrovascular P-glycoprotein may be a novel therapeutic strategy to protect the brain from beta-amyloid accumulation, and thereby impede the progression of Alzheimer's disease.

Topics: Alzheimer Disease; Amyloid; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Brain; Disease Models, Animal; Hypericum; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Phloroglucinol; Plant Extracts; Terpenes

Hypericum caprifoliatum Cham & Schlecht (Guttiferae) extracts have a potential antidepressant-like effect in rodents. However, the molecular mechanisms by which these extracts exert this effect remain unclear.. This study evaluated the effect of HC1, a fraction obtained from H. caprifoliatum enriched in phloroglucinol derivatives, on the Na⁺, K⁺ ATPase activity in mouse brain and verified the influence of veratrine on the effect of HC1 in the forced swimming test (FST).. Veratrine (0.06 mg/kg) and HC1 (360 mg/kg) were given alone or combined i.p. 60 and p.o. 30 min, respectively, before FST. The effect of single and repeated administration (once a day for 3 consecutive days) of HC1 (360 mg/kg) on Na⁺, K⁺ ATPase activity was evaluated ex vivo in the cerebral cortex and hippocampus of mice subjected or not to FST.. HC1 reduced the immobility time (103.15 ± 18.67 s), when compared to the control group (183.6 ± 9.51 s). This effect was prevented by veratrine (151.75 ± 22.19 s). Mice repeatedly treated with HC1 presented a significant increase in Na⁺, K⁺ ATPase activity, both in cerebral cortex (46 ± 2.41 nmol Pi/min·mg protein) and hippocampus (49.83 ± 2.31 nmol Pi/min·mg protein), in relation to the respective controls (30 ± 2.66 and 29.83 ± 2.31 nmol Pi/min·mg protein respectively).. The HC1 antidepressant-like effect on FST might be related to its capacity to inhibit Na⁺ influx. HC1 increases hippocampal and cortical Na⁺, K⁺ ATPase activities possibly through long-term regulatory mechanisms.

Topics: Animals; Antidepressive Agents; Cerebral Cortex; Depression; Disease Models, Animal; Hippocampus; Hypericum; Male; Mice; Phloroglucinol; Plant Extracts; Sodium; Sodium-Potassium-Exchanging ATPase; Swimming; Veratrine

Hypericum perforatum Linn. (Hypericaceae) (St. John's wort) attenuates opium withdrawal signs.. To explore the therapeutic potential of Hypericum perforatum in the management of opium-induced withdrawal syndrome.. The effect of the Hypericum perforatum hydro-ethanol extract was investigated for potential to reverse naloxone (0.25 mg/kg)-induced opium withdrawal physical signs. Rats received opium extract (80-650 mg/kg) twice daily for 8 days along with Hypericum perforatum (20 mg/kg, orally) twice daily in chronic treatment and the same single dose 1 h before induction of withdrawal syndrome in the acute treated group.. Hypericum perforatum reduced stereotype jumps and wet dog shake number in the chronic treatment compared to the saline control group (F(2, 24) = 3.968, p < 0. 05) and (F(2, 24) = 3.689, p < 0.05), respectively. The plant extract in the acutely treated group reduced diarrhea (F(2, 24) = 4.850, p < 0. 05 vs. saline). It decreased rectal temperature by chronic treatment at 30 min (F(2, 24) = 4.88, p < 0.05), 60 min (F(2, 240 = 5.364, p < 0.01) and 120 min (F(2, 24) = 4.907, p < 0.05).. This study reveals that the extract of Hypericum perforatum attenuates some physical signs of opium withdrawal syndrome possibly through direct or indirect interaction with opioid receptors. Further study is needed to clarify its mechanism.

Topics: Animals; Disease Models, Animal; Female; Hypericum; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Opium; Phytotherapy; Plant Components, Aerial; Plant Extracts; Rats, Sprague-Dawley; Substance Withdrawal Syndrome

We aimed to investigate the effects of herbal St. John's Wort (SJW) on transcriptional regulation of hepatic tryptophan 2, 3 - dioxygenase (TDO) enzyme activity and brain regional serotonin (5-HT) levels in rats exposed to forced swim test (FST). TDO mRNA expression was quantified using real-time reverse transcription polymerase chain (RT-PCR) reaction and brain regional indoleamines were determined by high performance liquid chromatography coupled to fluorescence detector. Behavioral analysis shows significant reduction in immobility time in SJW (500mg/kg/ml) administered rats. It was found that pretreatment of SJW to rats did not prevent stress-induced elevation in plasma corticosterone levels however it increases serotonin synthesis by virtue of inhibiting hepatic TDO enzyme activity and its gene expression, ascertaining the notion that there exists an inverse relationship between hepatic TDO enzyme activity and brain 5-HT. The drug also decreases serotonin turnover in all the brain areas (hypothalamus, hippocampus amygdala) in stressed rats endorsing its monoamine oxidase inhibition property. Inhibition of TDO enzyme activity and its gene expression by the drug provides new insights for the development of therapeutic interventions for stress related mental illnesses.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Brain; Corticosterone; Disease Models, Animal; Enzyme Inhibitors; Gene Expression Regulation, Enzymologic; Hypericum; Liver; Male; Motor Activity; Phytotherapy; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; RNA, Messenger; Serotonin; Stress, Psychological; Transcription, Genetic; Tryptophan Oxygenase; Up-Regulation

To evaluate the effects of montelukast and Hypericum perforatum against ischemia/reperfusion (I/R)-induced intestinal damage.. Twenty-eight hamsters were divided into 4 groups following midline abdominal laparotomy: control group (n = 7), I/R group (n = 7), montelukast and I/R (MIR) group (n = 7), and Hypericum perforatum and I/R (HPIR) group (n = 7). After 60 min of ischemia through obstruction of the superior mesenteric artery, 24 h of reperfusion was maintained. Ten minutes prior to the reperfusion period, the MIR group received 7 mg/kg of intraperitoneal montelukast and the HPIR group received 7 mg/kg of intraperitoneal Hypericum perforatum. Malondialdehyde, glutathione, myeloperoxidase, and cardiotrophin-1 levels were measured from blood samples. A semiquantitative histological evaluation was performed.. Montelukast and Hypericum perforatum significantly reduced malondialdehyde levels and increased glutathione levels compared to the I/R group (P < 0.008). A statistically significant difference was also found between the I/R group and MIR and HPIR groups in terms of myelqperoxidase levels (P < 0.008). The MIR and HPIR groups showed increased cardiotrophin- 1 levels compared to the control and I/R groups (P < 0.008 for all). The MIR and HPIR groups showed significantly lower histological scores compared to the I/R group (P = 0.03 and P = 0.007, respectively).. This study demonstrated the preventive effects of montelukast and Hypericum perforatum on I/R-induced intestinal injury.

Topics: Acetates; Animals; Cricetinae; Cyclopropanes; Disease Models, Animal; Glutathione; Hypericum; Intestines; Malondialdehyde; Mesenteric Artery, Superior; Mesocricetus; Plant Extracts; Protective Agents; Quinolines; Random Allocation; Reperfusion Injury; Sulfides

Hipericum perforatum is a well-known herbal for its antidepressant property. Recently, it has been shown to have nootropic effects against neurodegenerative disorders. The aim of the present study was to evaluate the protective role of chronic administration of two standardized extract of Hypericum perforatum SHP1 rich in hyperforin (6%) and SHP2 extract poor in hyperforin (0.2%) on the neurodegeneration induced by chronic administration of rotenone in rats. Quercetin in liposomes, one active constituent, was tested in the same experimental conditions. The animals received pretreatments with SHP1 (4 mg/Kg, ip), SHP2 (4 mg/Kg, ip) or quercetin liposomes (25 and 100 mg/kg, ip) 60 min before of rotenone injection (2.5 mg/kg) for 45 days. Pretreatment of the animals with SHP1 and SHP2 efficiently halted deleterious toxic effects of rotenone, revealing normalization of catalepsy in addition to amelioration of neurochemical parameters. Also, SHP1 reduced neuronal damage, diminishing substantia nigra dopaminergic cell death caused by the pesticide, indicating benefit of neuroprotective therapy. In general, the SHP1 was more active than SHP2. In addition, SHP1 inhibited the apoptotic cascade by decreasing Bax levels. The results presented here indicate that mainly hyperforin and quercetin, may be involved in the neuroprotective action of Hypericum standardized extracts. Combination of dietary antioxidants could provide better therapeutic advantage for the management of Parkinson, and possibly other neurodegenerative disorders. Therefore H. perforatum standardized extract enriched in hyperforin, could be a better alternative for depressed elderly patients with degenerative disorders exhibiting elevated oxidative stress status.

Topics: Analysis of Variance; Animals; Apoptosis Regulatory Proteins; Brain; Catalepsy; Corpus Striatum; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Fluorodeoxyglucose F18; Hypericum; Insecticides; Liposomes; Male; Maze Learning; Neurons; Neuroprotective Agents; Parkinson Disease; Phytotherapy; Positron-Emission Tomography; Quercetin; Rats; Rats, Wistar; Rotenone; Swimming

Despite a number of antimigraine drugs belonging to different pharmacological classes are available, there is a huge unmet need for better migraine pharmacotherapy. We here demonstrated the capability of Hypericum perforatum, popularly called St. John's wort (SJW), to relieve meningeal nociception in an animal model induced by administration of the nitric oxide (NO) donors glyceryl trinitrate (GTN) and sodium nitroprusside (SNP). GTN and SNP produced a delayed meningeal inflammation, as showed by the upregulation of interleukin (IL)-1β and inducible NO synthase (iNOS), and a prolonged cold allodynia and heat hyperalgesia with a time-course consistent with NO-induced migraine attacks. A single oral administration of a SJW dried extract (5mg/kg p.o.) counteracted the nociceptive behaviour and the overexpression of IL-1β and iNOS. To clarify the cellular pathways involved, the expression of protein kinase C (PKC) and downstream effectors was detected. NO donors increased expression and phosphorylation of PKCγ, PKCɛ and transcription factors, such as nuclear factor (NF)-κB, cyclic AMP response element binding protein (CREB), Signal Transducer and Activator of Transcription (STAT)-1. All these molecular events were prevented by SJW and hypericin, a SJW main component. In conclusion, SJW counteracted the NO donor-induced pain hypersensitivity and meningeal activation by blocking PKC-mediated pathways involving NF-κB, CREB, STAT1. These results might suggest SJW as an innovative and safe perspective for migraine pain.

Topics: Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Hypericum; Male; Meninges; Mice; Migraine Disorders; Nociception; Phytotherapy; Plant Extracts

Hypericum (H.) perforatum, popularly called St. John's Wort has been used traditionally for the treatment of anxiety, depression and as a nerve tonic. Large amount of clinical and animal experimental data demonstrate that H. perforatum acts by biochemical mechanisms similar to the tricyclic antidepressants or serotonin reuptake inhibitors. However, its efficacy in comparison to standard antidepressant drugs is not well studied. The present study evaluated H. perfortum extract in animal models of depression compared to clinically used antidepressants.. The effects of standardized extract of H. perforatum was compared with standard antidepressants using animal models of depression such as forced swim test (FST), yohimbine induced lethality test, pnetylenetetrazole (PTZ) induced convulsion and locomotor activity tests. Different doses of the plant extract and standard drugs were administered to rats or mice intraperitoneally (i.p).. In the FST, H. perforatum extract (30-90 mg/kg i.p.) caused a dose dependent reduction in immobility time in rats with maximal effect being 53% at 90 mg/kg. This effect was reversed at higher doses (100 mg/kg) showing a U-shaped dose response curve. Fluoxetine and imipramine (30-70 mg/kg i.p.) produced similar reduction in the immobility time in rats. Venlafaxine exhibited weak antidepressant effect. H. perforatum extract (30-100 mg/kg i.p.), dothiepin (10-50 mg/kg i.p.), fluoxetine (30-60 mg/kg i.p.) and venlafaxine (20-40 mg/kg i.p.) potentiated yohimbine induced lethality. PTZ induced toxicity was also enhanced with these agents. In the locomotor activity test H. perforatum decreased the locomotor counts of mice similar to standard antidepressants.. H. perforatum has antidepressant properties similar to standard antidepressants. The antidepressant profile of H. perforatum is closely related to the selective serotonin reuptake inhibitors class of antidepressants.

Topics: Animals; Antidepressive Agents; Depression; Disease Models, Animal; Hypericum; Male; Mice; Motor Activity; Pentylenetetrazole; Plant Extracts; Rats; Rats, Sprague-Dawley; Rats, Wistar; Yohimbine

Hypericum (H.) spp. has been used in traditional medicine for their anticonvulsant effect for many years. In spite of many works on this genus, little is known about H. scabrum. In this work, anticonvulsant activity of H. scabrum was investigated.. Anticonvulsant activity of aqueous extract was evaluated by pentylenetetrazole (PTZ) induced convulsion and picrotoxin induced convulsion. Also, nitric oxide radical scavenging was investigated as a possible mechanism involved.. Extract (125-500 mg kg-1, i.p.) significantly delayed the onset of PTZ induced convulsion. At 500 mg kg-1, 100% protection against mortality was observed. At this dose, it significantly prolonged the onset of picrotoxin induced convulsion in mice, too. It showed significant nitric oxide radical scavenging activity.. Mechanism of anticonvulsant activity may be through GABA and/or nitric oxide pathway.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Free Radical Scavengers; gamma-Aminobutyric Acid; Hypericum; Male; Medicine, Traditional; Mice; Nitric Oxide; Pentylenetetrazole; Picrotoxin; Plant Extracts; Seizures; Time Factors

The effects of Hypericum perforatum, a plant with antidepressant action, were evaluated in models of abnormal movements in rats, brought about by administration of fluphenazine or reserpine. The number of vacuous chewing movements (VCMs) and locomotor activity (the number of crossings and rears in the open field test) were measured. In experiment 1, rats received a single administration of fluphenazine enanthate (25 mg/kg, intramuscular) and/or daily treatment with H. perforatum (300 mg/kg, in place of drinking water) for 7 days. Fluphenazine increased VCMs and decreased locomotor activity. H. perforatum had no effect on either the number of VCMs or the locomotor activity. In experiment 2, rats received reserpine every 2 days for 6 days (0.5 mg/kg, subcutaneous) and/or H. perforatum (300 mg/kg, in place of drinking water) daily for 16 days beginning 10 days before the first administration of reserpine. Reserpine treatment increased VCMs and decreased locomotor activity. H. perforatum had no effect on either the number of VCMs or the number of rears but did prevent the effect of reserpine on the number of crossings. In conclusion, H. perforatum failed to protect against orofacial movements induced by fluphenazine or reserpine in rats.

Topics: Animals; Disease Models, Animal; Fluphenazine; Hypericum; Male; Mastication; Motor Activity; Movement Disorders; Plant Extracts; Rats; Rats, Wistar; Reserpine

Soluble β-amyloid peptides (Aβ) and small Aβ oligomers represent the most toxic peptide moieties recognized in brains affected by Alzheimer's disease (AD). Here we provide the first evidence that specific St. John's wort (SJW) extracts both attenuate Aβ-induced histopathology and alleviate memory impairments in APP-transgenic mice. Importantly, these effects are attained independently of hyperforin. Specifically, two extracts characterized by low hyperforin content (i) significantly decrease intracerebral Aβ42 levels, (ii) decrease the number and size of amyloid plaques, (iii) rescue neocortical neurons, (iv) restore cognition to normal levels, and (iv) activate microglia in vitro and in vivo. Mechanistically, we reveal that the reduction of soluble Aβ42 species is the consequence of a highly increased export activity in the bloodbrain barrier ABCC1transporter, which was found to play a fundamental role in Aβ excretion into the bloodstream. These data (i) support the significant beneficial potential of SJW extracts on AD proteopathy, and (ii) demonstrate for the first time that hyperforin concentration does not necessarily correlate with their therapeutic effects. Hence, by activating ABC transporters, specific extracts of SJW may be used to treat AD and other diseases involving peptide accumulation and cognition impairment. We propose that the anti-depressant and anti-dementia effects of these hyperforin-reduced phytoextracts could be combined for treatment of the elderly, with a concomitant reduction in deleterious hyperforin-related side effects.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Brain; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression Regulation; Hypericum; Maze Learning; Mice; Mice, Transgenic; Microglia; Multidrug Resistance-Associated Proteins; Peptide Fragments; Phagocytes; Phloroglucinol; Phytotherapy; Plant Preparations; Plaque, Amyloid; Terpenes; Time Factors

Topics: Animals; Cardiomyopathy, Dilated; Connexin 43; Disease Models, Animal; Hypericum; Male; Plant Extracts; Rats; Rats, Wistar

To explore the synergistic antidepressant effect of quercetin and hyperforin (HF, extracted from Hypericum perforatum).. Male ICR mice were divided into nine groups:blank control, positive control (Paroxetine, 10 mg/kg), quercetin groups (A: 5 mg/kg, B: 10 mg/kg, C: 20 mg/kg), Hypericum perforatum extract (HF 10 mg/kg),combination groups (A: quercetin 2.5 mg/kg + HF 5 mg/kg,B:quercetin 5 mg/kg + HF 5 mg/kg,C: quercetin 10 mg/kg + HF 5 mg/kg). All drugs were administered intragastrically. Reserpine reversal tests were used to compare the reversal effects of drugs on body temperature decline, eyelid ptosis and akinesia. Tail suspension test was used to compare immobility time in each group.. Combination group B showed no significant difference (P>0.05) compared with combination group C in reserpine reversal tests and tail suspension test. However, its body temperature reversal effect was significantly higher (P<0.01) than that of quercetin group B, and its effect in shortening immobility time was stronger than that of HF 10 mg/kg group (P<0.05) and quercetin group B (P<0.01).. The combination of quercetin and Hypericum perforatum extract in certain ratio has significant synergistic antidepressant effect in ICR mice.

Topics: Animals; Antidepressive Agents; Depression; Disease Models, Animal; Hypericum; Male; Mice; Mice, Inbred ICR; Plant Extracts; Quercetin

Hypericum perforatum L., a plant used in Chinese herbal medicine, has been proven effective against many viral diseases. In the present study, the therapeutic efficacy of an extract of H. perforatum (HPE) against influenza A virus (IAV) was investigated in mice. Whether HPE would be a promising agent for influenza treatment was evaluated by measuring the protection rate, mean survival days, lung index, and viral titer, as well as the secretion of IL-6, interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α), and interferon-gamma (IFN-γ) in lung tissue and serum on days 3 and 5 post-infection. The results showed that HPE could reduce the lung index and viral titer of mice infected with IAV, decrease mortality, and prolong the mean survival time. HPE decreased the concentration of IL-6 and TNF-α in lung tissue and serum on day 5 post-infection. In contrast, HPE enhanced the lung and serum levels of IL-10 and IFN-γ on the days 3 and 5 post-infection. Our study indicates that HPE has significant therapeutic efficacy for mice infected with IAV. The possible reasons for these results were concluded to be pertaining to up-regulating the expression of IL-10 and IFN-γ, and down-regulating the secretion of IL-6 and TNF-α in lung and serum.

Topics: Animals; Antiviral Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Female; Hypericum; Inflammation Mediators; Influenza A virus; Interferon-gamma; Interleukin-10; Interleukin-6; Lung; Male; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections; Ribavirin; Time Factors; Tumor Necrosis Factor-alpha; Viral Load

Curcumin is the active principle of Curcuma longa, one of the widely used components in the traditional system of medicine in India. Despite its efficacy in experimental studies aiming at neuronal disorders like depression, curcu-min's poor water solubility challenges the production of therapeutic formulations. This study investigates the antidepressant-like activity of novel water-soluble curcumin formulations, dispensed in three different concentrations. Further, the study comparatively evaluates St. John's wort (SJW), another herbal preparation.. These compounds were evaluated in the forced swimming test in mice, and the corresponding changes in the neurotransmitter levels were measured.. Three water-soluble curcumin formulations, C-5, C-20 and C-50 (50-200 mg/kg p.o.) decreased the immobility period, and increased serotonin and dopamine levels in the brain tissues. A subeffective dose (50 mg/kg) of these formulations enhanced the antidepressant-like effect of classical antidepressants with varied mechanisms of action. In addition, an SJW dose of 25 mg/kg showed a significant antidepressant-like effect in all the behavioral studies and also significantly increased brain neurotransmitter levels, especially that of serotonin. The effects produced by C-5 were comparable with those of SJW and fluoxetine, respectively.. In all these observations, the water-soluble formulations showed a significant antidepressant-like effect, including enhancement of neurotransmitter levels as compared to the similar dose of a conventional curcumin preparation. Thus, these formulations may be used as a novel treatment option in the management of mental depression.

Topics: Animals; Antidepressive Agents; Biogenic Amines; Brain; Chemistry, Pharmaceutical; Curcumin; Depression; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Therapy, Combination; Hypericum; Immobility Response, Tonic; Male; Mice; Mice, Inbred Strains; Motor Activity; Phytotherapy; Plant Extracts; Solubility; Time Factors

The protective effects of St John's Wort extract (SJ), ginsenosides (GS), and clomipramine (CPM) on chronic unpredictable mild stress (CUMS)-induced depression in rats were investigated by using a combination of behavioral assessments and metabonomics. Metabonomic analyses were performed using gas chromatography/mass spectrometry in conjunction with multivariate and univariate statistical analyses. During and at the end point of the chronic stress experiment, food consumption, body weight, adrenal gland, thymus and spleen indices, behavior scores, sucrose consumption, and stress hormone levels were measured. Changes in these parameters reflected characteristic phenotypes of depression in rats. Metabonomic analysis of serum, urine, and brain tissue revealed that CPM and SJ mainly attenuated the alteration of monoamine neurotransmitter metabolites, while GS affected both excitatory/inhibitory amino acids and monoamine neurotransmitter metabolites. GS also attenuated the stress-induced alterations in cerebrum and peripheral metabolites to a greater extent than CPM and SJ. These results provide important mechanistic insights into the protective effects of GS against CUMS-induced depression and metabolic dysfunction.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Antidepressive Agents; Behavior, Animal; Body Weight; Clomipramine; Depressive Disorder; Disease Models, Animal; Food Deprivation; Gas Chromatography-Mass Spectrometry; Ginsenosides; Hypericum; Male; Metabolome; Metabolomics; Multivariate Analysis; Phenotype; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Spleen; Stress, Psychological; Sucrose; Swimming; Thymus Gland

Hypericum perforatum L., known as St. John's wort (SJW), is used as a phytotherapeutic agent for the treatment of mild to moderate forms of depression.. The aim of the present study was to evaluate the effect of SJW extract (STW 3-VI; 250 and 500 mg/kg; p.o.) and fluoxetine (10 mg/kg, p.o.) on genes involved in the pathogenesis of depression using a chronic restraint stress (CRS) model in rats. Of particular interest was the assessment of similarities and differences between SJW extract and fluoxetine on the gene expression level in two different brain regions.. Hypothalamic and hippocampal tissues were analyzed using the Affymetrix gene chip Rat Genome 230 2.0 Array, which comprises more than 30,000 rat transcripts. Limma program and PANTHER database were used to evaluate the microarray data. Genes involved in the pathways of inflammatory processes (Mapk8), oxidative stress (Gpx3, Gstm3, Sod3) or Alzheimer's disease (Sncb, Apbb1ip) were altered by both fluoxetine and SJW extract. For all groups, several signaling pathways were identified which could provide a link between the various hypotheses of depression.. In conclusion, microarray analysis proved to be a valuable tool to identify a large number of genes and resulting pathways that may serve as novel drug targets or predict drug responsiveness for SJW or fluoxetine. Based on our comprehensive analysis, it was possible to identify similarities and differences between SJW and fluoxetine which may help to better understand their molecular action and, in addition, help to find novel treatment strategies for stress-related depression.

Topics: Animals; Antidepressive Agents; Depression; Disease Models, Animal; Dose-Response Relationship, Drug; Fluoxetine; Gene Expression Regulation; Hippocampus; Hypericum; Hypothalamus; Male; Microarray Analysis; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley

Extracts of Hypericum, Passiflora and Valeriana are used for the treatment of mild depression and anxiety. We were interested whether a combination of Hypericum and Passiflora exerts comparable effects to Hypericum alone. We used two well-established models for investigating extracts for their anti-depressant activity, namely the effects on synaptic uptake of serotonin and the forced-swimming-test. We show here for the first time, that Passiflora significantly enhances the pharmacological potency of Hypericum in both models. Our data suggest that anti-depressive therapeutic effects of Hypericum are possible with lower doses, when it is combined with Passiflora, than with mono-preparations of Hypericum.

Topics: Animals; Antidepressive Agents; Biological Transport; Depression; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Hypericum; Passiflora; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Serotonin; Swimming; Synapses

Extracts of Hypericum perforatum (St. John's wort) have been traditionally recommended for a wide range of medical conditions, in particular mild-to-moderate depression. The present study was designed to investigate the effect of Hypericum perforatum treatment in a mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone administration.. CD1 mice were submitted to 7 weeks corticosterone administration and then behavioral tests as Open Field (OF), Novelty-Suppressed Feeding (NSF), Forced Swim Test (FST) were performed. Cell proliferation in hippocampal dentate gyrus (DG) was investigated by both 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) immunohistochemistry techniques and stereological procedure was used to quantify labeled cells. Golgi-impregnation method was used to evaluate changes in dendritic spines in DG. Hypericum perforatum (30 mg/Kg) has been administered for 3 weeks and then neural development in the adult hippocampus and behavioral changes have been examined.. The anxiety/depressive-like state due to chronic corticosterone treatment was reversed by exogenous administration of Hypericum perforatum; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment, whereas a long term treatment with Hypericum perforatum prevented the corticosterone-induced decrease in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density that was ameliorated by Hypericum perforatum administration.. These results provide evidence of morphological adaptations occurring in mature hippocampal neurons that might underlie resilient responses to chronic stress and contribute to the therapeutic effects of chronic Hypericum perforatum treatment.

Topics: Animals; Anxiety; Behavior, Animal; Cell Proliferation; Corticosterone; Dendrites; Depression; Disease Models, Animal; Doublecortin Protein; Hippocampus; Hypericum; Male; Mice; Mice, Inbred Strains; Neurogenesis; Phytotherapy; Plant Extracts; Stem Cells; Stress, Physiological

Beneficial effects of St. John's wort (Hypericum perforatum) in the treatment of stress-evoked memory impairment were recently described. In this study, we tested a hypothesis that St. John's wort alleviates stress- and corticosterone-related memory impairments by restoring levels of synaptic plasticity proteins: neuromoduline (GAP-43) and synaptophysin (SYP) in hippocampus and prefrontal cortex. Stressed and corticosterone-treated rats displayed a decline in the acquisition of spatial working memory (p < 0.001) in the Barnes maze (BM). Chronic administration of H. perforatum (350 mg kg(-1) for 21 days), potently and significantly improved processing of spatial information in the stressed and corticosterone-injected rats (p < 0.001). Also, St Johns' wort statistically significantly (p < 0.05) increased levels of GAP-43 and SYP, respectively in the hippocampi and prefrontal cortex as measured by western immunoblotting. We found that H. perforatum prevented the deleterious effects of both chronic restraint stress and prolonged corticosterone administration on working memory measured in the BM test. The herb significantly (p < 0.01) improved hippocampus-dependent spatial working memory in comparison with control and alleviated some other negative effects of stress on cognitive functions. These findings increase our understanding of the reaction of the hippocampus and prefrontal cortex to stressful assaults and provide new insight into the possible actions of H. perforatum in the treatment of patients with impaired adaptation to environmental stressors and simultaneously suffering from cognitive impairment.

Topics: Animals; Blotting, Western; Corticosterone; Disease Models, Animal; GAP-43 Protein; Hippocampus; Hypericum; Male; Maze Learning; Memory, Short-Term; Neuronal Plasticity; Plant Extracts; Prefrontal Cortex; Rats; Rats, Wistar; Stress, Psychological; Synaptophysin

Cholesterol gallstone disease (CGD) results from a biochemical imbalance of lipids and bile salts in the gallbladder bile. We investigated whether the xenobiotic receptor pregnane X receptor (PXR) has a role in pathogenesis of CGD.. Wild-type, PXR-null (PXR-/-), and CGD-sensitive C57L mice were placed on a lithogenic diet and then analyzed for CGD at the biochemical, histological, and gene-regulation levels.. Loss of PXR sensitized mice to lithogenic diet-induced CGD, characterized by decreases in biliary concentrations of bile salts and phospholipids and an increases in the cholesterol saturation index and formation of cholesterol crystals. The decreased bile acid pool size in PXR-/- mice that received lithogenic diets was associated with reduced expression of cholesterol 7α-hydroxylase, the rate-limiting enzyme of cholesterol catabolism and bile acid formation. The reduced expression of cholesterol 7α-hydroxylase most likely resulted from activation of farnesoid X receptor and induction of fibroblast growth factor 15 in the intestine. In C57L mice given the PXR agonist, pregnenolone-16α-carbonitrile, or the herbal medicine, St John's wort, cholesterol precipitation was prevented by increases in concentrations of biliary bile salt and a reduced cholesterol saturation index. PXR prevented CGD via its coordinate regulation of the biosynthesis and transport of bile salts in the liver and intestine.. PXR maintains biliary bile acid homeostasis and may be developed as a therapeutic target for CGD.

Topics: Animals; Bile; Bile Acids and Salts; Biological Transport; Cholesterol 7-alpha-Hydroxylase; Cholesterol, Dietary; Disease Models, Animal; Fibroblast Growth Factors; Gallstones; Gene Expression Regulation; Hypericum; Intestinal Mucosa; Intestines; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Phospholipids; Plant Preparations; Pregnane X Receptor; Pregnenolone Carbonitrile; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; Time Factors

To observe the effect of combined administration of intragastric perfusion of extract of Hypericum Perforatum L (HP-L) and electroacupuncture (EA) of "Baihui" (GV 20) and "Yamen" (GV 15) on behavior and brain microcirculation in depression rats.. Female SD rats were randomized into control, model, lower-dose of HP-L (lower-dose in short, 10 mg/kg), lower-dose+ EA, higher-dose (20 mg/kg) and higher-dose+ EA groups (n = 10/group). Depression model was established by lonely raising and chronic unpredictable mild stress (tail cramping, water-deprivation, fasting, electrical shock stimulation, etc. ) for 21 days. EA (2 Hz, 1 mA) was applied to "Baihui"(GV 20) and "Yamen"(GV 15) for 20 min, once daily for 14 days. Changes of ethology including glucose-consumption during 1 h, crossing and rearing scores of open-field test during 3 min (for assessing the rats' locomoto)and laser Doppler flowmetry values of cortical regional cerebral bloodflow (r CBF) were detected, and Morris water maze test (for assessing the rats' learning-memory ability) was conducted.. In comparison with the control group, the sucrose consumption, crossing and rearing scores of open-field test, the average swimming velocity (ASV). the ratios of path length and swimming duration near the hidden-platform and the path length and swimming duration far from the platform of Morris water maze test during 70 seconds, and the cortical r CBF value in the model group were decreased significantly (P < 0.01), while the total swimming distance and escape latency in the model group increased apparently (P < 0.01). Compared to the model group, the average sucrose consumption, crossing and rearing scores of open-field test, the ASV, and the ratios of path length and swimming duration near the platform and those far from the platform in the lower-dose. lower-dose + EA, higher-dose and higher-dose + EA groups, and the cortical r CBF in the lower-dose + EA and higher-dose + EA groups were increased considerably (P < 0.05, P < 0.01). The total swimming distances and escape latencies of lower-dose, lower-dose + EA, higher-dose and higher-dose + EA groups were significantly shortened in comparison with the model group (P < 0.05, P < 0.01). The sucrose consumption and crossing score were significantly higher in the higher-dose + EA group than the lower-dose group (P < 0.05). The escape latency was significantly shorter in the higher-dose + EA group than in the lower-dose group (P < 0.05). No significant differences were found among the lower-dose, lower-dose + EA and higher-dose groups the sucrose consumption, crossing score and escape latency: among the lower-dose, lower-dose + EA, higher-dose and higher-dose + EA groups in the rearing score and ASV; among the lower-dose, higher-dose and model groups in the cortical r CBF (P > 0.05).. EA can enhance the effect of extract of HP-L in increasing sucrose consumption, crossing score and cerebral blood flow, and in shortening escape latency in depression rats, which may contribute to their effect in improving depression. But HP-L itself has no effect on cortical microcirculation.

Topics: Administration, Topical; Animals; Brain; Combined Modality Therapy; Depression; Disease Models, Animal; Drugs, Chinese Herbal; Electroacupuncture; Ethology; Female; Humans; Hypericum; Microcirculation; Random Allocation; Rats; Rats, Sprague-Dawley

Hypericum enshiense L. H. Wu et F. S. Wang is a new species of Hypericum occurring in China, which was first identified and denominated by our laboratory. No research has been reported on the antidepressant activity and chemical constituents of this new species. In this study, the qualitative and quantitative analyses of the chemical constituents in the hydroalcoholic extract of this species were performed using HPLC/DAD/ESI-MS online method. Hypericin, pseudohypericin and some flavonoids were identified or tentatively identified. Furthermore, H. enshiense had a high content of hypericins than H. perforatum. In addition, the antidepressant activity of the hydroalcoholic extract of the species was investigated using forced swimming test (FST) and tail suspension test (TST). The extract significantly shortened the immobility time in FST and TST, while did not alter the locomoter activity of mice. These results suggested for the first time that the hydroalcoholic extract of H. enshiense might possess potential antidepressant-like activity in the animal behavioral models, and this species might act as a new potential resource for developing antidepressants to treat depressive disorders.

Topics: Animals; Anthracenes; Antidepressive Agents; Behavior, Animal; China; Depression; Disease Models, Animal; Flavonoids; Hindlimb Suspension; Hypericum; Male; Mice; Mice, Inbred Strains; Motor Activity; Perylene; Phytotherapy; Plant Components, Aerial; Plant Extracts; Swimming

The antinociceptive profile of St. John's Wort (SJW) was investigated in mice in a condition of acute thermal and chemical pain, together with the mechanism that might underlie this effect. A dried extract of SJW induced a prolonged antinociception that persisted for 120 minutes after administration. The thermal antinociception was prevented by naloxone and by the protein kinase C (PKC) activator PMA, whereas the chemical antinociception was prevented by PMA, remaining naloxone insensitive. A chloroform (CHL) and a methanol (MET) fraction, obtained to investigate the involvement of the SJW main components, hyperforin and hypericin/flavonoid, respectively, increased pain threshold with a time course comparable to the dried extract. The CHL antinociception was prevented by naloxone, whereas the MET antinociception was antagonized by PMA. Purified hyperforin and hypericin showed an antinociceptive efficacy comparable to CHL and MET, respectively. Conversely, flavonoids were devoid of any effect. The administration of yohimbine and atropine did not modify SJW, CHL and MET antinociception. These results indicate that both CHL and MET fractions mediate the SJW-induced antinociception. In particular, the presence of hypericin was fundamental to induce both thermal and chemical antinociception through the inhibition of the PKC activity, whereas hyperforin selectively produced a thermal opioid antinociception.. This article presents evidence of a persistent thermal and chemical antinociception of SJW that is mainly mediated by PKC-inhibiting mechanisms. These findings identify important targets for a longer-acting activation of endogenous pain systems and should potentially help clinicians who seek safe, tolerable, and prolonged treatments for pain relief.

Topics: Acetic Acid; Analgesics; Analgesics, Opioid; Animals; Anthracenes; Chromatography, High Pressure Liquid; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Administration Schedule; Drug Compounding; Hypericum; Male; Mice; Naloxone; Naltrexone; Narcotic Antagonists; Pain; Pain Measurement; Pain Threshold; Perylene; Phorbol Esters; Phytotherapy; Protein Kinase C; Quercetin; Somatostatin; Spectrometry, Mass, Electrospray Ionization; Statistics, Nonparametric; Time Factors

Hypericum perforatum is a medicinal plant species containing many polyphenolic compounds, namely flavonoids and phenolic acids. In this study we evaluate the effect of Hypericum perforatum in animal model of periodontitis.. Periodontitis was induced in adult male Sprague-Dawley rats by placing a nylon thread ligature around the lower 1st molars. Hypericum perforatum was administered at the dose of 2 mg/kg os, daily for eight days. At day 8, the gingivomucosal tissue encircling the mandibular first molar was removed.. Periodontitis in rats resulted in an inflammatory process characterized by edema, neutrophil infiltration and cytokine production that was followed by the recruitment of other inflammatory cells, production of a range of inflammatory mediators such as NF-κB and iNOS expression, the nitration of tyrosine residues and activation of the nuclear enzyme poly (ADP-ribose) polymerase; apoptosis and the degree of gingivomucosal tissues injury. We report here that Hypericum perforatum exerts potent anti-inflammatory effects significantly reducing all of the parameters of inflammation as described above.. Taken together, our results clearly demonstrate that treatment with Hypericum reduces the development of inflammation and tissue injury, events associated with periodontitis.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Cytokines; Disease Models, Animal; Edema; Flavonoids; Hypericum; Inflammation Mediators; Male; Mouth Mucosa; Neutrophil Infiltration; Periodontitis; Phenols; Phytotherapy; Plant Extracts; Poly(ADP-ribose) Polymerases; Polyphenols; Rats; Rats, Sprague-Dawley; Tyrosine

Various species of Hypericum genus have been used in the Canary Islands as sedative, diuretic, vermifuge, wound healing, antihysteric and antidepressant agent. Studies have shown that methanol extract of Hypericum grandifolium Choisy is active in tetrabenazine-induced ptosis and forced swimming tests. In the current study, the aqueous, butanol and chloroform fractions obtained from the methanol extract as well as three sub-fractions derived from the chloroform fraction were evaluated for their central nervous effects in mice, particularly their antidepressant activity.. The central nervous effect of different fractions and sub-fractions of Hypericum grandifolium was evaluated in mice using various behavioural models including locomotor and muscle relaxant activity, forced swimming test, effect on normal body temperature, barbiturate-induced sleep, tetrabenazine-induced syndrome and 5-hydroxytryptohan-induced head twitches and syndrome.. We found that the butanol and chloroform fractions and all sub-fractions showed an antidepressant effect in the forced swimming test, the chloroform fraction being the most active. They produced no effects or only a slight depression of locomotor activity. Chloroform fraction significantly increased the pentobarbital-induced sleeping time, produced a slight but significant hypothermia and antagonized tetrabenazine-induced ptosis, whereas the butanol fraction produced a slight potentiation of 5-HTP-induced head twitches and syndrome.. The present results, together with previous pharmacological and phytochemical data, indicated that Hypericum grandifolium possess antidepressant-like effects in mice and that different constituents, such as the flavonoids and the benzophenone derivatives, could be responsible at least in part for the antidepressant effects observed for this species.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Body Temperature; Depression; Disease Models, Animal; Hypericum; Male; Medicine, Traditional; Mice; Motor Activity; Plant Components, Aerial; Plant Extracts; Spain; Swimming

Present study has investigated acute effects of Saint Johns Wort (SJW, 500mg/kg) administration on behavioral, neuroendocrine responses and serotonergic activity following forced swim test (FST) exposure in rats. The results show that SJW increased swimming and climbing behaviour of rats during FST exposure. Swim stress produced significant reduction in serum total tryptophan (P<0.01), increase in corticosterone (P<0.01) and 5-hydroxytryptamine (serotonin, 5-HT) turnover in hypothalamus by 100% (P<0.01), amygdala by 148 % (P<0.01), and hippocampus by 41% (P<0.05) when compared with unstressed saline injected group. SJW in swim stressed rats when compared with saline injected stressed rats altered neither lowered serum tryptophan nor enhanced HPA axis response, however 5HT was found to be increased by 110% (P<0.01), 163% (P<0.01) and 172% (P<0.01), in hypothalamus, amygdala and hippocampus respectively. 5-hydroxyindoleacetic acid (5HIAA) was also found to be increased in hypothalamus by 74% (P<0.01), amygdala by 45% (P<0.01) and hippocampus by 143.5% (P<0.01). Further SJW administration in unstressed rats showed decrease in tryptophan (P<0.01), increase in corticosterone (P<0.01), 5HT was found to be decreased in hypothalamus (47%, P<0.01) and in amygdala (13 %, P<0.05) with no change in hippocampus, while 5HIAA was found increased in hypothalamus by 58 %(P<0.01), amygdale by 203 % (P<0.01) and hippocampus by 171% (P<0.01). The data shows that SJW affects circulating tryptophan and corticosterone in absence of conditioned stress but not in its presence. In conclusion, SJW increases intraneuronal 5HT metabolism but inhibits its release under adverse conditions proving its anxiolytic property. Thus, these effects produced by the SJW add to our understanding of the interactions between SJW and stress induced behavioral, neuroendocrine and serotonergic alterations.

Topics: Amygdala; Animals; Anti-Anxiety Agents; Behavior, Animal; Brain; Corticosterone; Disease Models, Animal; Hippocampus; Hydroxyindoleacetic Acid; Hypericum; Hypothalamo-Hypophyseal System; Hypothalamus; Male; Pituitary-Adrenal System; Plant Preparations; Rats; Rats, Wistar; Serotonin; Stress, Psychological; Swimming; Tryptophan

Multiple sclerosis is an inflammatory and demyelinating disease of the central nervous system which mainly affects young adults. To overcome wide spectrum troublesome symptoms of multiple sclerosis which affects the quality of life both in patients and their families, new drugs and remedies have been examined and offered. The preclinical beneficial effects of different medicines have mostly been examined in an animal model of multiple sclerosis called experimental allergic encephalomyelitis (EAE). In this study we have tested a traditionally used natural (herbal-marine) product called MS(14) in EAE mice. EAE mice were fed with MS(14) containing diet (30%) on the immunization day and monitored for 20 days. The results show that while clinical scores and therefore severity of the disease was progressive in normal-fed EAE mice, the disease was slowed down in MS(14)-fed EAE mice. Moreover, while there were moderate to severe neuropathological changes in normal fed mice, milder changes were seen in MS(14) fed mice.

Topics: Administration, Oral; Animal Feed; Animals; Apium; Biological Products; Brain; Demyelinating Diseases; Disease Models, Animal; Disease Progression; Encephalomyelitis, Autoimmune, Experimental; Female; Hypericum; Intracranial Hemorrhages; Iran; Mice; Necrosis; Penaeidae

Present study shows the effects of St John's Wort (SJW) (20 mg/kg) on swim stress induced changes in tryptophan (TRP) metabolism and disposition in rats. The results show that after forced swim test (FST) hepatic tryptophan pyrrolase (holo and total) activities were significantly decreased (P<0.001). Liver TRP was increased (P<0.001) while serum TRP was decreased (P<0.01). Brain TRP, 5-hydroxytryptamine (5-HT, Serotonin) and 5-hydroxyindole acetic acid (5-HIAA) concentrations were increased (P<0.001), similarly immobility time during swim test was also increased. SJW pretreated FS group of rats showed reduced holo enzyme activity (P<0.001) while increase in total and apo enzyme activities (P<0.001). There was significant decrease in liver TRP (P<0.01), serum TRP (P<0.05), brain TRP (P<0.001), 5-HT (P<0.001) and 5-HIAA (P<0.001) concentrations with reduction in immobility time during swim test when compared with saline injected FS group. SJW injected group but when compared with untreated controls showed significant increase in total and apo enzyme activities (P<0.001) while holo enzyme activity was decreased (P<0.001), serum TRP, brain TRP and 5-HIAA levels were significantly decreased (P<0.001). Changes in 5-HT concentrations were not significant. It is concluded that SJW treatment alter stress induced augmented 5-HT levels by decreasing precursor availability to the brain and that serotonergic system is involve in the mechanism of action of the drug.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Brain; Depression; Disease Models, Animal; Hydroxyindoleacetic Acid; Hypericum; Injections, Intraperitoneal; Male; Motor Activity; Plant Extracts; Rats; Rats, Wistar; Serotonin; Stress, Psychological; Swimming; Tryptophan; Tryptophan Oxygenase

Ocular neovascularization is a leading cause of blindness in ischemic retinopathies. Hypericin is an active ingredient in the medical herb St. John's Wort (SJW). Because hypericin inhibits intracellular signaling pathways that are believed to participate in the regulation of angiogenesis, we investigated the actions of hypericin and SJW in retinal neovascularization, using a mouse model of oxygen-induced retinopathy (OIR).. C57BL/6 neonatal mice were exposed to a 75% concentration of oxygen from postnatal day 7 (P7) to P12 and returned to room air from P12 to P17 to induce retinal neovascularization. SJW (15 mg/kg/day), hypericin (15, 45, or 135 mug/kg/day), or vehicle was given by gavage once a day for five days from P12 to P17. To quantify the area of retinal neovascularization and vasoobliteration, we stained retinas with isolectin B4 at P17. Phosphorylation of extracellular signal-regulated kinase (ERK) in ischemic retinas was determined by western blot analysis. To estimate retinal vascularization, we stained retinas with isolectin B4 at P7 after treatment with SJW, hypericin, or vehicle from P3 to P7.. Gavage administration of hypericin or SJW significantly inhibited the degree of retinal neovascularization, but did not affect the area of retinal vasoobliteration in a mouse model of OIR. Both SJW and hypericin had no effect on normal vascularization over the treatment time course. Treatment with SJW or hypericin reduced phosphorylation of ERK in the retina.. These data suggest that hypericin and SJW reduce pathological retinal neovascularization and that administration of these agents could have clinical utility for treatment of ischemic retinopathies.

Topics: Angiogenesis Inhibitors; Animals; Anthracenes; Disease Models, Animal; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Female; Hypericum; Ischemia; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic; Oxygen; Perylene; Phosphorylation; Retina; Retinal Diseases; Retinal Neovascularization

This study was done to assess the effects of Urtica dioica, Plantago major and Hypericum perforatum L herbal mixture in the MCIA rat model. In addition, a new pathological and clinical arthritis lesion assessment was developed. Sprague-Dawley (SD) rats were immunized with bovine type II collagen and muramyl dipeptide (MDP). Commercial herbal extracts were administered daily to the rats after the immunization for the course of experiment (90 days). Rats were boosted with a second collagen-MDP emulsion 60 days after the first immunization. Paws were daily evaluated macroscopically for redness, swelling, distortion, or ankylosis of the joints. On the day of sacrifice, rat paws were assessed for histopathologic changes. Herbal mixture administration decreased the clinical lesion manifestation in the MCIA rat model and led to development of similar or slightly more severe histopathological lesions compared to rats that did not receive the treatment. The clinical arthritis signs appeared as early as 13 days after the first MDP/collagen injection and with peak incidence at 20 days post-immunization. Histopathologically, animals showed changes ranging from mild to very severe. Administration of the herbal mixture used in this study had a clinical therapeutic effect on the course of the clinical manifestations in the MCIA model, but the herbal treatment had no such effect on the histopathological lesion development and even led to slightly more severe lesions. Rats in the MCIA model developed prominent clinical and histopathological changes that were comparable to rheumatoid arthritis (RA) lesions in humans.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Arthritis, Rheumatoid; Cattle; Collagen Type II; Disease Models, Animal; Humans; Hypericum; Joints; Male; Phytotherapy; Plant Extracts; Plantago; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Urtica dioica

Hypercholesterolemia, high cholesterol diet and oxidative stress increase serum total cholesterol and LDL cholesterol levels resulting in increased risk for development of atherosclerosis. Antioxidants play an important role in inhibiting and scavenging radicals, thus providing protection to humans against infectious and degenerative diseases. Literature shows that the antioxidant activity is high in medicinal plants. Realizing the fact that, this study was carried out to determine the effect of ethanol extract of Hypericum lysimachioides Boiss var lysimachioides (Guttifera) on serum lipid levels and serum lipid peroxidation in hypercholesterolemic rabbits. The rabbits were divided into four groups and these groups were fed with diets containing standard laboratory diet (Group I), standard laboratory diet and ethanol extracts of H. lysimachioides (HL) (50mg/kg body weight) (Group II), standard laboratory diet, ethanol extracts of HL (50mg/kg body weight) and cholesterol (100mg/kg body weight) (Group III), and finally standard laboratory diet and cholesterol (100mg/kg body weight) (Group IV), for 5 weeks. Feeding cholesterol increased serum cholesterol and LDL cholesterol levels significantly in Group IV as compared to the other groups. Ethanol extract of HL with high cholesterol diet significantly lowered LDL cholesterol and total cholesterol levels in the rabbits of Group III as compared to the Group IV. The level of serum triacylglycerol was found to be similar to all comparison groups. HDL cholesterol levels were also increased significantly in Groups II and III as compared to Group IV. Statistically significant difference was found in Group IV as compared to all other groups. The ethanol extract of HL with high cholesterol diet significantly lowered the serum MDA levels in the rabbits of Group III compared to the Group IV. The histopathological findings confirmed that the ethanol extract of HL restrained the progression of the hydropic degeneration and fatty changes in the liver and some atherosclerotic lesions in the aorta. The in vitro antioxidant activities of ethanol extract of HL was also evaluated. The free radical-scavenging properties of HL (IC(50)=28 microg/ml) were studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay system. Since plant phenolic compound is one of the phytochemicals possessing radical scavenging activity, the amount of total phenolic compound was also determined in ethanol extract of HL and total phenolic content of one-

Topics: Animals; Antioxidants; Aorta; Cholesterol, HDL; Cholesterol, LDL; Diet, Atherogenic; Disease Models, Animal; Hypercholesterolemia; Hypericum; Lipid Peroxidation; Liver; Male; Plant Extracts; Rabbits; Thiobarbituric Acid Reactive Substances

Histomorphological changes in murine fibrosarcoma after photodynamic therapy (PDT) based on the natural photosensitizer hypericin were evaluated. C3H/DiSn mice were inoculated with fibrosarcoma G5:1:13 cells. When the tumour reached a volume of 40-80 mm(3) the mice were intraperitoneally injected with hypericin, either in a single dose (5 mg/kg; 1 or 6 h before laser irradiation) or two fractionated doses (2.5 mg/kg; 6 and 1 h before irradiation with laser light; 532 nm, 70 mW/cm(2), 168 J/cm(2)). All groups of PDT-treated animals with single and fractionated hypericin dosing presented primary vascular reactions including vascular dilatation, congestion, thrombosis and oedema. Two hours after PDT there were necrotic changes with small, rather focal appearance. One day after therapy the necrotic areas were enhanced, often affecting a complete superficial layer of tumour tissue. Necrotic areas were accompanied with inflammation and haemorrhages.

Topics: Animals; Anthracenes; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Disease Models, Animal; Fibrosarcoma; Humans; Hypericum; Injections, Intraperitoneal; Male; Mice; Mice, Inbred C3H; Perylene; Photochemotherapy; Photosensitizing Agents; Phytotherapy; Plant Extracts; Radiation Dosage

Ethanol extracts of the aerial parts of six Hypericum species, H. barbatum, H. androsaemum, H. richerii, H. hirsutum, H. perforatum and H. perforatum cultivated on mountain Tara were tested for antiinflammatory activity in comparison with indomethacin (IND) using the carrageenan-induced rat paw edema test. It was found that all examined extracts produced antiinflammatory activity, particularly those from H. hirsutum, and both wild and cultivated H. perforatum. A dose-dependent antiinflammatory effect was especially pronounced in extracts showing some lower antiinflammatory activity. There was no correlation between the amount of hypericin in the extracts and their antiinflammatory activity.

Topics: Animals; Anthracenes; Anti-Inflammatory Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Hypericum; Indomethacin; Perylene; Plant Extracts; Rats

This study investigated, in mice, the antidepressant like effect of hyperfoliatin, a prenylated phloroglucinol derivative isolated from the aerial parts of Hypericum perfoliatum, as well as its action on monoaminergic systems. In the forced-swimming test, hyperfoliatin dose-dependently reduced immobility time. Immobility was interpreted as an expression of "behavioural despair", which could be a component of depression syndrome. The effect of hyperfoliatin did not result from the stimulation of animal motor activity. Hyperfoliatin inhibited, in a concentration-dependent manner, the [(3)H]-dopamine, [(3)H]-serotonin and [(3)H]-noradrenaline synaptosomal uptakes, but did not prevent the binding of specific ligands to the monoamine transporters. These data suggest that the antidepressant-like effect of hyperfoliatin on the forced-swimming test is probably associated to monoamine uptake inhibition, due to a mechanism of action different from that of known antidepressants.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Depression; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Hypericum; Male; Mice; Motor Activity; Neurotransmitter Uptake Inhibitors; Norepinephrine; Phloroglucinol; Phytotherapy; Plant Components, Aerial; Plant Extracts; Serotonin; Swimming; Triterpenes

St John's Wort (Hypericum perforatum) is the main herbal species used to treat depression. The products available on the pharmaceutical and dietary supplement markets are obtained by a variety of preparation processes and their pharmacological effects may differ significantly. The purpose of this study therefore was to investigate the effect of different St John's Wort commercial preparations available on the French market. Only one preparation gave significant results in the forced swimming test.

Topics: Animals; Body Weight; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Freezing Reaction, Cataleptic; Hypericum; Mice; Plant Extracts; Swimming

The methanol extract from Hypericum hircinum leaves exhibited in vitro inhibition of monoamine oxidases (MAO). Bioassay-guided fractionation led to the isolation of quercetin and five compounds identified for the first time from H. hircinum. Quercetin was the only compound with a selective inhibitory activity against MAO-A, with an IC50 value of 0.010 microM. To explain MAO selective inhibition at the molecular level, a computational study was carried out by conformational search and docking techniques using recently determined crystallographic models of both enzymatic isoforms. An in vivo study in mice was carried out using the forced swimming test in order to elucidate the behavioral effects of quercetin.

Topics: Animals; Disease Models, Animal; Hypericum; Inhibitory Concentration 50; Mice; Molecular Conformation; Molecular Structure; Monoamine Oxidase Inhibitors; Motor Activity; Plant Leaves; Plants, Medicinal; Quercetin; Swimming

The major protein constituent of amyloid deposits in Alzheimer's disease (AD) is the amyloid beta-peptide (Abeta). In the present work, we have determined the effect of hyperforin an acylphloroglucinol compound isolated from Hypericum perforatum (St John's Wort), on Abeta-induced spatial memory impairments and on Abeta neurotoxicity. We report here that hyperforin: (1) decreases amyloid deposit formation in rats injected with amyloid fibrils in the hippocampus; (2) decreases the neuropathological changes and behavioral impairments in a rat model of amyloidosis; (3) prevents Abeta-induced neurotoxicity in hippocampal neurons both from amyloid fibrils and Abeta oligomers, avoiding the increase in reactive oxidative species associated with amyloid toxicity. Both effects could be explained by the capacity of hyperforin to disaggregate amyloid deposits in a dose and time-dependent manner and to decrease Abeta aggregation and amyloid formation. Altogether these evidences suggest that hyperforin may be useful to decrease amyloid burden and toxicity in AD patients, and may be a putative therapeutic agent to fight the disease.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloidosis; Analysis of Variance; Animals; Bridged Bicyclo Compounds; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Escape Reaction; Hippocampus; Hypericum; Male; Maze Learning; Microinjections; Neuroprotective Agents; Phloroglucinol; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Terpenes; Time Factors

This study aimed at verifying a hypothesis that St. John's wort (Hypericum perforatum) alleviates stress-induced memory impairments. Administration of Hypericum perforatum (350 mg kg(-1) daily for 21 days) significantly enhanced recall of passive avoidance behavior (PAB), but had no effect on the acquisition of conditioned avoidance responses (CARs). Rats stressed chronically (2 h daily for 21 days) displayed diminished recall of the PAB and this effect was abolished by St John's wort. Chronic administration of the "equivalent" to the stress dose of exogenous corticosterone (5 mg kg(-1) daily for 21 days) also impaired recall of PAB, and this effect was also reversed by Hypericum perforatum. None of our treatments produced significant motor coordination impairments as tested in a 'chimney' test. It appears that H. perforatum prevents stress-induced deterioration of memory in rats.

Topics: Animals; Anti-Inflammatory Agents; Avoidance Learning; Chronic Disease; Conditioning, Psychological; Corticosterone; Disease Models, Animal; Hypericum; Male; Mental Recall; Motor Activity; Phytotherapy; Powders; Rats; Rats, Wistar; Restraint, Physical; Stress, Physiological

Diarrhea is a common dose-limiting toxicity associated with cancer chemotherapy, in particular for drugs such as irinotecan (CPT-11), 5-fluouracil, oxaliplatin, capecitabine and raltitrexed. St. John's wort (Hypericum perforatum, SJW) has anti-inflammatory activity, and our preliminary study in the rat and a pilot study in cancer patients found that treatment of SJW alleviated irinotecan-induced diarrhea. In the present study, we investigated whether SJW modulated various pro-inflammatory cytokines including interleukins (IL-1beta, IL-2, IL-6), interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) and intestinal epithelium apoptosis in rats. The rats were treated with irinotecan at 60 mg/kg for 4 days in combination with oral SJW or SJW-free control vehicle at 400 mg/kg for 8 days. Diarrhea, tissue damage, body weight loss, various cytokines including IL-1beta, IL-2, IL-6, IFN-gamma and TNF-alpha and intestinal epithelial apoptosis were monitored over 11 days. Our studies demonstrated that combined SJW markedly reduced CPT-11-induced diarrhea and intestinal lesions. The production of pro-inflammatory cytokines such as IL-1beta, IFN-gamma and TNF-alpha was significantly up-regulated in intestine. In the mean time, combined SJW significantly suppressed the intestinal epithelial apoptosis induced by CPT-11 over days 5-11. In particular, combination of SJW significantly inhibited the expression of TNF-alpha mRNA in the intestine over days 5-11. In conclusion, inhibition of pro-inflammatory cytokines and intestinal epithelium apoptosis partly explained the protective effect of SJW against the intestinal toxicities induced by irinotecan. Further studies are warranted to explore the potential for STW as an agent in combination with chemotherapeutic drugs to lower their dose-limiting toxicities.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Camptothecin; Cytokines; Diarrhea; Disease Models, Animal; Down-Regulation; Drug Therapy, Combination; Hypericum; Intestinal Mucosa; Irinotecan; Male; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley

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

Topics: Animals; Anticonvulsants; Cyclic GMP; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Electroshock; Ethanol; Hypericum; Injections, Intraperitoneal; Lethal Dose 50; Medicine, Traditional; Mice; NG-Nitroarginine Methyl Ester; Nitric Oxide; Pentylenetetrazole; Plant Components, Aerial; Plant Extracts; Receptors, N-Methyl-D-Aspartate; Seizures; Water

Clinical studies have demonstrated that the antidepressant efficacy of Hypericum perforatum extract is comparable to that of classic antidepressants, such as imipramine. The role played by its components, particularly hypericin and hyperforin, has been examined in different experimental models of depression. The present study was carried out in order to verify the hypothesis that hyperforin is the main active antidepressant component. For this purpose we evaluated the activity of a dry extract from a subspecies of H. perforatum, H. perforatum spp. angustifolium, which has a higher hyperforin content than H. perforatum perforatum, in a series of experimental models of depression. The models used are based on the development of hyporeactivity to aversive stimuli induced by unavoidable stress exposure in rats. The extract of H. perforatum angustifolium presented an efficacy that was similar to that obtained with a treatment with imipramine or H. perforatum perforatum. Furthermore, in the models used the H. perforatum angustifolium extract was active at doses eight times lower than those necessary to produce a comparable activity with H. perforatum extract.

Topics: Animals; Antidepressive Agents; Bridged Bicyclo Compounds; Depression; Disease Models, Animal; Dose-Response Relationship, Drug; Hypericum; Imipramine; Male; Phloroglucinol; Phytotherapy; Plant Extracts; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Stress, Psychological; Terpenes

Chronic fatigue syndrome (CFS) is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various body systems. The etiology of CFS remains unclear; however, a number of studies have shown that oxidative stress may be involved in its pathogenesis. In the present study, a mouse model of CFS was used in which mice were forced to swim for one 6-minute session on each day for 15 days and the immobility period was recorded. There was a significant increase in immobility period in saline-treated mice on successive days. Intraperitoneal treatment with the potent antioxidants carvedilol (5 mg/kg) and melatonin (5 mg/kg) produced a significant reduction in immobility period. Similar results were observed with herbal preparations administered orally: Withania somnifera (100 mg/kg), quercetin (50 mg/kg), and St. John's wort (Hypericum perforatum L., 10 mg/kg). Biochemical analysis revealed that chronic swimming significantly induced lipid peroxidation and decreased glutathione (GSH) levels in the brains of mice. The rats also showed decreased levels of antioxidant defense enzymes, superoxide dismutase (SOD), and catalase. Co-administration of antioxidants carvedilol, melatonin, W. somnifera, quercetin or St. John's wort significantly reduced lipid peroxidation and restored the GSH levels decreased by chronic swimming in mice. Further, the treatment increased levels of SOD in the forebrain and of catalase. The findings strongly suggest that oxidative stress plays a significant role in the pathophysiology of CFS and that antioxidants could be useful in the treatment of CFS.

Topics: Animals; Antioxidants; Brain; Carbazoles; Carvedilol; Catalase; Disease Models, Animal; Fatigue Syndrome, Chronic; Glutathione; Hypericum; Lipid Peroxidation; Male; Melatonin; Mice; Oxidative Stress; Phytotherapy; Plant Extracts; Propanolamines; Quercetin; Superoxide Dismutase; Swimming; Withania

The present study was carried out using mice model of chronic fatigue syndrome (CFS) in which mice were forced to swim everyday for 7 days for a 6 min session. There was a significant increase in despair behavior (immobility period) in saline treated mice on successive days. Treatment with potent antioxidants carvedilol (5 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) produced a significant reduction in immobility period. Similar results were observed with herbal products St. John's Wort (Hypericum perforatum L) (10 mg/kg, p.o.) and GS-02 (20 mg/kg, p.o.). Fluoxetine, a selective serotonin reuptake inhibitor produced a significant effect only on first and second day of its treatment. Biochemical analysis revealed that chronic swim test significantly increased lipid peroxidation and catalase levels in whole brains of mice. There was a decrease in the levels of super oxide dismutase (SOD) and glutathione reductase (GSH) in the brain. Administration of carvedilol, melatonin, GS-02 and St. John's Wort restored the levels of lipid peroxidation and glutathione. The enzymes SOD and catalase were also restored. Fluoxetine affected the biochemical variables not to the same extent as other treatments. The findings of the present study suggest that oxidative stress might play a significant role in the pathophysiology of CFS. Thus antioxidants and herbal products like St. Johns wort and GS-02 could be useful in the treatment of CFS.

Topics: Animals; Antioxidants; Brain; Carbazoles; Carvedilol; Catalase; Disease Models, Animal; Fatigue Syndrome, Chronic; Fluoxetine; Glutathione; Glutathione Reductase; Hypericum; Lipid Peroxidation; Male; Melatonin; Mice; Oxidative Stress; Phytotherapy; Propanolamines; Selective Serotonin Reuptake Inhibitors; Superoxide Dismutase; Swimming

The treatment of non-selected depressed patients with a hydro-alcoholic extract of Hypericum perforatum has been reported to have an efficacy similar to that of classical antidepressants. The effects of H. perforatum on three animal depression models have been studied: (a) an acute form of escape deficit (ED) induced by unavoidable stress; (b) a chronic model of ED, which can be maintained by the administration of mild stressors on alternate days; (c) a model of anhedonia based on the finding that repeated stressors prevent the development of appetitive behavior induced by vanilla sugar in satiated rats fed ad libitum. H. perforatum: (i) acutely protects animals from the sequelae of unavoidable stress; (ii) reverts the chronic escape deficit state maintained by repeated stressors and (iii) preserves the animal's capacity to acquire motivated appetitive behavior. Exposure to chronic stress not only induces escape deficit, but also decreases extraneuronal levels of dopamine in the nucleus accumbens shell; both behavioral and neurochemical effects are reverted by long-term treatment with antidepressants. Three-week treatment with H. perforatum reverted the chronic stress effect on extraneuronal dopamine in the nucleus accumbens. A consistent body of data in the literature suggests that, among the components of H. perforatum extract, hyperforin is the compound (or one of the compounds) responsible for the antidepressant activity. We compared the efficacy of the total extract with the efficacy of hyperforin after p.o. administration. In the acute-escape deficit model, hyperforin showed a potency of about ten times that of the total extract in protecting rats from the sequelae of unavoidable stress. Thus, hyperforin appears to be the most likely active component responsible for the antidepressant activity of H. perforatum.

Topics: Animals; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Bridged Bicyclo Compounds; Chronic Disease; Depression; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Electroshock; Fluoxetine; Hypericum; Imipramine; Microdialysis; Phloroglucinol; Plant Extracts; Rats; Stress, Physiological; Terpenes

The total methanol crude extracts and petroleum ether, chloroform, and methanol fractions obtained from Hypericum species, H. caprifoliatum, H. carinatum, H. connatum, H. cordatum, H. myrianthum, H. piriai, H. polyanthemum and H. brasiliense, all native to South Brazil, were assayed for monoamine oxidase A (MAO A) and MAO B inhibitory activity in rat brain mitochondrial preparations at concentrations ranging from 1 to 20microg mL(-1). Three benzopyrans, HP1 (6-isobutyryl-5,7-dimethoxy-2,2-dimethylbenzopyran), HP2 (7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethylbenzopyran) and HP3 (5-hydroxy-6-isobutyryl-7-methoxy-2,2dimethylbenzopyran) isolated from H. polyanthemum were also tested at maximal concentrations of 150, 150 and 75/microM, respectively. The lipophilic extracts of H. polyanthemum, H. caprifoliatum and H. piriai displayed MAO A inhibitory activity greater than 50%. Among the benzopyrans, only HP3 showed significant activity, with an IC50 value of 22 microM. The total methanol crude extracts of aerial parts from H. carinatum, H. connatum, H. cordatum, H. polyanthemum and H. piriai were evaluated for antidepressant activity in the Porsolt's forced swimming test in Wistar rats (270 mg kg(-1) day(-1); i.p); however, none of them showed activity.

Topics: Animals; Antidepressive Agents; Brain; Brazil; Depression; Disease Models, Animal; Enzyme Inhibitors; Hypericum; Mitochondria; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Plant Extracts; Rats; Rats, Wistar; Swimming

Hypericum hookerianum Wight and Arnott of the family Hypericaceae is a well-known plant among the 20 different species of Hypericum found in India. Because of its use as a wound-healing agent in traditional practices and literature references, the present study was undertaken to evaluate the wound-healing potential of this plant.. Methanol extracts of the leaves (HHLM) and stems (HHSM) of H. hookerianum were studied for their wound-healing properties in the form of ointment, using two types of wound models in 36 rats. Ointments of the dried extract of the leaves and stems of this plant were applied in two different concentrations (5% w/w and 10% w/w ointment of extracts in simple ointment base) in both the wound models used in the present study. The effects were studied on incision (skin-breaking strength) and excision (percent wound contraction and epithelialization time) wound models.. The methanol extract of both leaves and stem of H. hookerianum; 72 white albino rats of either gender containing six groups for each experimental model with six animals in each group.. The extract ointments at both concentrations performed significant in both the wound models. The leaf extract in both concentrations showed greater activity than the stem. Ointments of both extracts of H. hookerianum showed significant effects on wound contraction, wound closure time, tensile strength, regeneration of tissues at the wound site, among other effects. All these effects were comparable to those of a standard drug, nitrofurazone ointment (0.2% w/w). This investigation confirms the use of aerial parts of H. hookerianum as a potential wound-healing agent, a property known from folklore medicine.

Topics: Animals; Disease Models, Animal; Female; Hypericum; Male; Ointments; Plant Extracts; Plant Leaves; Plant Stems; Plants, Medicinal; Rats; Rats, Wistar; Tensile Strength; Treatment Outcome; Wound Healing

A standardised 50% aqueous ethanolic extract of Indian Hypericum perforatum (IHp) was investigated for its antidepressant activity on various experimental paradigms of depression, viz. behavioural despair (BD), learned helplessness (LH), tail suspension (TS) and reserpine-induced hypothermia (RIH) tests in rats and mice. Pilot studies indicated that single dose administration of IHp had very little or no acute behavioural effects, hence the IHp was administered orally at two dose levels (100 and 200 mg/kg, p.o.) once daily for three consecutive days, while imipramine (15 mg/kg, i.p.), a clinically used antidepressant agent, was administered acutely to rats (CF strain, 150 +/- 10 g) and mice (Wistar strain, 23 +/- 2 g) of either sex as the standard drug. Controls animals were treated similarly with equal volume of vehicle (0.3% carboxymethyl cellulose). Indian Hypericum perforatum extract showed significant antidepressant activity on all the paradigms of depression used. Thus IHp and imipramine treatments significantly reduced the immobility time in BD and TS tests. Significant reduction in escape failures was also observed in LH test. In RIH test IHp and imipramine inhibited reserpine induced hypothermia in a dose dependent manner. The observed antidepressant activity of IHp was qualitatively comparable to that induced by imipramine.

Topics: Animals; Antidepressive Agents; Depression; Disease Models, Animal; Female; Hypericum; Imipramine; Male; Mice; Plant Extracts; Plants, Medicinal; Rats