hypericum and Body-Weight

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

Hypericum genus is traditionally known for its medicinal use and its therapeutic and antioxidant effects. However, the toxic effect of this plant has not been much explored. Our study aimed at investigating the effect of Hypericum humifusum (Hh) leaf extracts on oxidative stress parameters in male rats. For it, we first focused on the phytochemical analysis of the aqueous and methanolic extracts of Hh leaves. Hence, Wistar rats were treated per gavage for 30 days and divided into Control (1 mL/rat, distilled water), A200 group (200 mg/kg body weight (bw) aqueous extract), A400 group (400 mg/kg bw aqueous extract), M10 group (10 mg/kg bw methanolic extract), M20 group (20 mg/kg bw methanolic extract). The phytochemical analysis revealed the presence of tannins, flavonoids, steroids, carbohydrates, and phenolic compounds. Biochemical and histological investigations were performed in plasma and liver tissue. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) levels. At the same time, alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) were assayed in plasma samples. Histological study was also conducted in liver. We showed that Hh extracts reduced relative liver weight and increased ALT, AST, LDH activities in treated groups compared to control group. These results were associated with an increase of MDA levels and a decrease of antioxidant enzyme activities (CAT and SOD) in liver tissues of treated rats. Histology of liver demonstrated several alterations showing necrosis, altered hepatocytes and lymphocyte migration mainly in A200 group and dilated sinusoids, foamy appearance of hepatocytes and lymphocyte accumulation in the other treated groups. This original work indicated that chronic consumption of Hh leaf extracts has no antioxidant effect but instead it induces oxidative stress and enhances markers of cell damage which was confirmed by histological study of liver rats.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Biomarkers; Blood Cell Count; Body Weight; Catalase; Hypericum; L-Lactate Dehydrogenase; Liver; Malondialdehyde; Methanol; Organ Size; Oxidative Stress; Phytotherapy; Plant Extracts; Plant Leaves; Rats, Wistar; Superoxide Dismutase; Water

A high-fat diet (HFD) causes deficits in learning and memory by increasing oxidative stress. Antioxidants are known to improve learning and memory. Since Hypericum scabrum (H. scabrum) extract is rich in antioxidants, the aim of this study was to investigate the effects of the administration of H. scabrum extract on passive avoidance learning (PAL), novel object recognition (NOR), and locomotor activity in male rats on a HFD. Fifty-four male Wistar rats (weighing 220 ± 10 g) were divided into the following six groups: (1) Control (standard diet), (2) Ext100 (standard diet supplemented with 100 mg/kg extract once/day), (3) Ext300 (standard diet supplemented with 300 mg/kg extract once/day), (4) HFD (high-fat diet), (5) HFD + Ext100, and (6) HFD + Ext300. Rats in these groups were maintained on their respective diets for 3 months. In the PAL test, the step-through latencies in the retention test (STLr) were significantly higher in the HFD + extract group than in the HFD group. The time spent in the dark compartment (TDC) was significantly lesser and the time spent in exploring the novel object was significantly greater in the HFD + extract group than in the HFD group. In the HFD-fed rats, the activity of catalase had significantly decreased, and level of malondialdehyde had significantly increased; H. scabrum extract administration significantly reversed these changes. In conclusion, these results suggested that the administration of H. scabrum extract and its strong antioxidant properties enhanced learning and memory and reversed the memory impairment induced by chronic HFD consumption.

Topics: Animals; Antioxidants; Avoidance Learning; Body Weight; Catalase; Diet, High-Fat; Hypericum; Lipid Peroxidation; Male; Malondialdehyde; Memory; Motor Activity; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Recognition, Psychology

The continuous and long-term consumption of a high-fat diet (HFD) leads to weight gain and obesity. A HFD and obesity increase the risks of psychiatric disorders, such as anxiety and depression. In this study, we investigated the effects of a Hypericum Scabrum (H. scabrum) extract, which is an antioxidant, on anxiety in rats fed a long-term HFD. Sixty male Wistar rats were divided into the following six groups: (1) Control (standard diet), (2) Ext100 [standard diet supplemented with extract (100 mg/kg once/day)], (3) Ext300 [standard diet supplemented with extract (300 mg/kg once/day)], (4) HFD, (HFD), (5) HFD + Ext100, and (6) HFD + Ext300. The groups were fed their diet for 3 months. Anxiety was measured with the elevated plus-maze test. At the end of the study, blood samples were taken, and biochemical parameters and oxidative stress biomarker levels were determined in the plasma. Compared to the control group, the HFD group exhibited significant decreases in both the time in the open arms and number of entries into the open arms. H. scabrum extract supplementation significantly increased these parameters in the HFD-fed groups. The HFD significantly increased serum malondialdehyde levels and significantly decreased total glutathione levels, while H. scabrum extract supplementation significantly reversed these parameters. In conclusion, these results showed that a HFD increased anxiety behavior. In contrast, H. scabrum extract supplementation had anxiolytic effects and reversed the effects of the HFD, which suggested that the effects of H. scabrum extract supplementation were due to its strong antioxidant properties.

Topics: Animals; Antioxidants; Anxiety; Body Weight; Diet, High-Fat; Glutathione; Glutathione Peroxidase; Hypericum; Lipid Peroxidation; Male; Malondialdehyde; Motor Activity; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar

Oxidative stress and inflammation play a key role in the initiation and progression of diabetic nephropathy (DN). The present study aimed to investigate the possible protective effect of hypericum perforatum (HP) against DN. Rats were allocated into six groups: control, received normal saline; diabetic untreated (DM), received single dose of streptozotocin (STZ) after injection of nicotinamide (NA); gliclazide, received STZ,NA + gliclazide (10 mg/kg); DM + HP50, DM + HP100, DM + HP200, received STZ,NA and HP 50, 100, 200 mg/kg, respectively. Gliclazide and HP were administered daily via gavage for 8 weeks. Serum glucose, insulin, kidney function and histopathological picture were assessed. Furthermore, oxidative/nitrosative stress, inflammatory cytokines, apoptotic and fibrotic markers were measured. Diabetic untreated group showed increase in serum glucose, urea, creatinine with albuminurea. Renal expression of protein for nuclear factor kappa-B (NF-кB), renal expression of inducible nitric oxide synthase (iNOS), cyclooxygenase II (COXII), collagen IV, fibronectin were elevated. Malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intracellular adhesion molecule (ICAM-1), monocellular chemoattractant protein-1 (MCP-1), tumour growth factor- β (TGF-β), caspase-3 and cytochrome c contents were also increased consequently with decline of serum insulin, expression of peroxisome proliferator-activated receptor (PPARγ), renal reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Treatment with either gliclazide or HP mitigated the deleterious effects of STZ on the tested parameters. These findings indicate for the first time that HP may have a renoprotective effect against DN through reduction of oxidative/nitrosative stress, enhancement of antioxidant defense mechanisms, decline of inflammatory cytokines, antifibrotic, antiapoptotic and blood glucose lowering properties.

Topics: Animals; Antioxidants; Apoptosis; Body Weight; Collagen Type IV; Cyclooxygenase 2; Cytoprotection; Diabetic Nephropathies; Fibronectins; Gene Expression Regulation, Enzymologic; Gliclazide; Hypericum; Inflammation Mediators; Kidney; Male; NF-kappa B; Nitric Oxide Synthase Type II; Oxidative Stress; PPAR gamma; Rats; Rats, Wistar; Transforming Growth Factor beta

The widely-used Chinese medicinal herb Hypericum japonicum, also known as Hypericum japonicum Thunb or Tianjihuang, displays potent anti‑carcinogenic effects against liver cancer. However, the molecular mechanism underlying the therapeutic effects of Hypericum japonicum remains to be elucidated. The present study investigated the in vivo efficacy of ethyl acetate extract of Hypericum japonicum (EAEHJ) against tumor growth in an H22 cell‑bearing liver cancer mouse model. Treatment with EAEHJ significantly reduced tumor weight, but had no effect on murine body weight. The results of the present study also showed that EAEHJ induced H22 cell apoptosis in vivo. In addition, the anti‑carcinogenic effects of EAEHJ were investigated in vitro. The results of the present study demonstrate that both phospholipid asymmetry in the plasma membrane and mitochondrial membrane potential were deregulated in HepG2 human hepatoma cells, following treatment with EAEHJ. Treatment with EAEHJ also increased the ratio of pro‑apoptotic B‑cell lymphoma 2 (Bcl‑2)‑associated X protein (Bax) to anti‑apoptotic Bcl‑2, and activated the caspase‑9 signaling pathway. These results suggest that EAEHJ is able to trigger the apoptosis of liver cancer cells via the mitochondria-dependent pathway.

Topics: Acetates; Animals; Anticarcinogenic Agents; Apoptosis; bcl-2-Associated X Protein; Body Weight; Caspase 3; Caspase 9; Cell Line, Tumor; Gene Expression Regulation; Hep G2 Cells; Humans; Hypericum; Liver Neoplasms; Membrane Potential, Mitochondrial; Mice; Mitochondria; Plant Extracts; Signal Transduction; Xenograft Model Antitumor Assays

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

Since oxidative stress is implicated in the pathophysiology of dementia and depression, this study was designed to investigate the pro-oxidant activity of rotenone, the protective role of standardized extract of Hypericum perforatum (SHP), as well as the mRNA levels of antioxidant enzymes, in brain homogenates of rats following exposure to rotenone and SHP extract. Quercetin in liposomes, one active constituent, was tested in the same experimental conditions to serve as a positive control. The animals received pretreatment with SHP (4 mg/kg) or quercetin liposomes (25 and 100 mg/kg) 60 min before of rotenone injection (2 mg/kg). All treatments were given intraperitoneally in a volume of 0.5 ml/kg body weight, for 45 days. Rotenone treatment increased activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and levels of malondialdehyde (MDA). The content of reduced glutathione (GSH) was decreased due to chronic rotenone treatment. Rotenone significantly induced the gene expression of CuZnSOD, MnSOD; CAT and GPx in brain. In contrast, SHP extract exerted an antioxidant action which was related with a decreased of MnSOD activity and mRNA levels of some antioxidant enzymes evaluated. Liposomal quercetin treatment resulted in a significant preservation of the activities of antioxidant enzymes and a decreased in the mRNA levels of these antioxidant enzymes. One possible mechanism of action of SHP extract may be related to quercetin in protecting neurons from oxidative damage. Therefore standardized extract of H. perforatum could be a better alternative for depressed elderly patients with degenerative disorder exhibiting elevated oxidative stress status.

Topics: Analysis of Variance; Animals; Antioxidants; Body Weight; Drug Interactions; Gene Expression Regulation; Glutathione Peroxidase; Hypericum; Liposomes; Malondialdehyde; Oxidative Stress; Quercetin; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Rotenone; Superoxide Dismutase; Time Factors; Uncoupling Agents

A large number of plants belonging to the Hypericum family are known to possess strong antitumor properties. The methanol extract of H. hookerianum Wight and Arnott stem (MEHH) exhibited potent in vitro cytotoxic activity against various cancerous cell lines. In the present study, the high performance liquid chromatography (HPLC) standardized MEHH was tested for in vivo antitumor properties against Ehrlich ascites carcinoma (EAC) tumor bearing mice at 100, 200, and 400 mg/kg body weight doses given orally once daily for 14 days. The results indicate that administration of the extract not only increased the survival of animals with ascites tumor, decreased the body weight induced by the tumor burden, and reduced packed cell volume and viable tissue cell count, but also altered many hematological parameters changed during tumor progression, indicating the potent antitumor nature of the extract. Among the three doses tested, the 200 mg/kg body weight dose was found to be the most potent.

Topics: Animals; Antineoplastic Agents, Phytogenic; Body Weight; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Female; Hypericum; Male; Methanol; Mice; Neoplasm Transplantation; Phytotherapy; Plant Extracts; Plant Stems; Survival Analysis; Time Factors

An herbal health care supplement, St John's Wort (SJW, Hypericum perforatum) has become widely used in the treatment of depression, and is known to interact with therapeutic drugs. Here we report a preventive effect of SJW on cisplatin nephrotoxicity in rats. Rats were given SJW (400 mg/kg/day, p.o.) for 10 consecutive days, and were injected with cisplatin (5 mg/kg, i.v.) on the day after the final SJW treatment. Cisplatin treatment increased the serum creatinine level, which is an index of nephrotoxicity, to 1.51+/-0.22 mg/dl (mean+/-SE) from 0.28+/-0.05 mg/dl (control) on day 5 after the cisplatin injection. This increase fell significantly to 0.86+/-0.13 mg/dl by pre-treatment with SJW. Cisplatin-induced histological abnormality of the kidney was blocked by pre-treatment with SJW. When SJW was administered for 10 days, the amounts of renal metallothionein (MT) and hepatic multidrug resistance protein 2 (Mrp2) were increased to 164.8+/-13.0% and 220.8+/-39.3% (mean+/-SE) of controls, respectively. GSH levels in the kidney and liver were not changed. Total and free cisplatin concentration in serum was not influenced by SJW treatment. In conclusion, the results suggest that pre-treatment with SJW may diminish cisplatin nephrotoxicity.

Topics: Animals; Antineoplastic Agents; ATP-Binding Cassette Transporters; Body Weight; Cell Membrane; Cisplatin; Creatinine; Drug Interactions; Glutathione; Hypericum; Kidney; Kidney Diseases; Male; Metallothionein; Rats; Rats, Wistar

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

CPT-11 is a DNA topoisomerase I inhibitor for the therapy of colorectal cancer, whereas St. John's Wort (Hypericum perforatum, SJW) is a widely used herbal anti-depressant. This study aimed to investigate the effects of co-administered SJW on the toxicities and pharmacokinetics of CPT-11 and the underlying mechanisms. The body weight loss, gastrointestinal and hematological toxicities induced by CPT-11, and the pharmacokinetic parameters of CPT-11 were evaluated in rats pretreated with SJW or vehicle. Rats treated with CPT-11 alone experienced rapid decrease in body weight, whereas co-administration of SJW with CPT-11 resulted in lesser body weight loss. The gastrointestinal and hematological toxicities following CPT-11 injection were both alleviated in the presence of SJW. The rat pharmacokinetics of both CPT-11 and its metabolite SN-38 were significantly altered in presence of SJW. In conclusion, co-administered SJW significantly ameliorated the toxicities induced by CPT-11. The protective effect of SJW may be partially due to pharmacokinetic interaction between CPT-11 and SJW.

Topics: Animals; Antineoplastic Agents, Phytogenic; Area Under Curve; Blood Cell Count; Body Weight; Camptothecin; Chromatography, High Pressure Liquid; Diarrhea; Drug Interactions; Half-Life; Hypericum; Intestinal Diseases; Intestinal Mucosa; Irinotecan; Male; Rats; Rats, Sprague-Dawley; Reference Standards; Reproducibility of Results

The popularity of St. John's wort (Hypericum perforatum) for the treatment of depression is increasing and, in recent years, concerns about its use during pregnancy and breastfeeding have emerged. The purpose of this study was to investigate, in Wistar rats, the effects of a treatment with hypericum administered prenatally and during breastfeeding (from 2 weeks before mating to 21 days after delivery). Two doses of the extract were chosen, 100 mg/kg per day, which, based on surface area, is comparable to the dose administered to humans, and 1000 mg/kg per day. A microscopical analysis of livers, kidneys, hearts, lungs, brains, and small bowels was performed. A severe damage was observed in the livers and kidneys of animals euthanized postnatally on days 0 and 21. The lesions were more severe with the higher dose and in animals that were breastfed for 21 days; however, an important renal and hepatic damage was evident also with the dose of 100 mg/kg per day. In addition, similar serious hepatic and renal lesions were evident also in animals that were exposed to hypericum only during breastfeeding. In particular, a focal hepatic damage, with vacuolization, lobular fibrosis, and disorganization of hepatic arrays was evident; in the kidney, a reduction in glomerular size, disappearance of Bowman's space, and hyaline tubular degeneration were found. The results obtained in this study indicate that further, appropriate histological studies should be performed in other animal species to better evaluate the safety of hypericum extracts taken during pregnancy and breastfeeding.

Topics: Animals; Animals, Newborn; Body Weight; Female; Hypericum; Kidney; Lactation; Liver; Plant Extracts; Pregnancy; Pregnancy, Animal; Rats; Rats, Wistar

We previously showed that a methanolic extract of St John's wort (SJW) (Hypericum) and hypericin, one of its active constituents, both have delayed regulation of genes that are involved in the control of the hypothalamic-pituitary-adrenal (HPA) axis. Hyperforin, another constituent of SJW, is active in vitro and has been proposed to be the active constituent for therapeutic efficacy in depression. We therefore examined if hyperforin has delayed effects on HPA axis control centers similar to those of Hypericum and hypericin. We used in situ hybridization histochemistry to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) oral administration of two hyperforin preparations, fluoxetine (positive control), and haloperidol (negative control) on the expression of genes involved in the regulation of the HPA axis. Fluoxetine (10 mg/kg) given daily for 8 weeks, but not 2 weeks, significantly decreased levels of corticotropin-releasing hormone (CRH) mRNA by 22% in the paraventricular nucleus (PVN) of the hypothalamus and tyrosine hydroxylase (TH) mRNA by 23% in the locus coeruleus. Fluoxetine increased levels of mineralocorticoid (MR) (17%), glucocorticoid (GR) (18%), and 5-HT(1A) receptor (21%) mRNAs in the hippocampus at 8, but not 2, weeks. Comparable to haloperidol (1 mg/kg), neither the hyperforin-rich CO(2) extract (27 mg/kg) nor hyperforin-trimethoxybenzoate (8 mg/kg) altered mRNA levels in brain structures relevant for HPA axis control at either time point. These data suggest that hyperforin and hyperforin derivatives are not involved in the regulation of genes that control HPA axis function.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Anti-Bacterial Agents; Antidepressive Agents; Body Weight; Brain; Bridged Bicyclo Compounds; Corticosterone; Drug Interactions; Hypericum; Hypothalamo-Hypophyseal System; Immunohistochemistry; In Situ Hybridization; Male; Organ Size; Phloroglucinol; Phosphoproteins; Pituitary-Adrenal System; Plant Extracts; Pro-Opiomelanocortin; Radioimmunoassay; Rats; Receptor, Serotonin, 5-HT1A; Receptors, Glucocorticoid; Receptors, Mineralocorticoid; RNA, Messenger; Terpenes; Time Factors; Transcription, Genetic; Tyrosine 3-Monooxygenase

This investigation was designed to determine the ability of St. John's wort (SJW), a readily available antidepressant, to induce various hepatic drug metabolizing enzymes. SJW (140 or 280 mg/kg/day) was administered to male Swiss Webster mice for 1, 2, or 3 weeks. Enzymatic activity was analyzed in hepatic microsomes for all of the following drug metabolizing enzymes: CYP3A, CYP1A, CYP2E1, and UDP-glucuronosyltransferase (UDPGT). The catalytic activity of CYP1A was unchanged from control following any dose or duration of SJW, while both CYP3A and CYP2E1 catalytic activities were increased 2-fold by both SJW concentrations but only following 3 weeks of administration. Results from Western immunoblotting studies supported the changes in catalytic activity, as protein levels for CYP2E1 and CYP3A were increased (2.5-fold and 6-fold, respectively) following 3 weeks of SJW administration. Additionally, the catalytic activity of the conjugation enzyme UDPGT was unchanged from control following all SJW treatments. These results indicate that in the mouse moderate doses of SJW cause an increase in the catalytic activity and polypeptide levels of CYP2E1 and CYP3A but only following 21 days of administration, while the catalytic activity of CYP1A and UDPGT activity remain unaffected.

Topics: Animals; Aryl Hydrocarbon Hydroxylases; Blotting, Western; Body Weight; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2E1; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Enzyme Induction; Glucuronosyltransferase; Hypericum; Liver; Male; Mice; Mice, Inbred Strains; Microsomes, Liver; Organ Size; Oxidoreductases, N-Demethylating; Plant Extracts; Time Factors

This investigation was designed to determine whether St. John's wort (SJW)(435 mg/kg/d), a readily available antidepressant, or its purported active constituents hypericin (1 mg/kg/d) and hyperforin (10 mg/kg/d) were able to induce various hepatic cytochrome P450 (CYP450) isoforms. SJW, hypericin and hyperforin were administered to male Swiss Webster mice for four consecutive days and hepatic microsomes were prepared on day 5. None of the three treatments resulted in a statistical change in total hepatic CYP450 (SJW treated 0.95 +/- 0.09 nmol/mg vs control 1.09 +/- 0.14 nmol/mg). Furthermore, the catalytic activities of CYP1A2. CYP2E1 and CYP3A were unchanged from control following all three treatments as determined by ethoxyresorufin O-deethylation, p-nitrophenol hydroxylation and erythromycin N-demethylation respectively. Additionally, western immunoblotting demonstrated that there was no significant change in the polypeptide levels of any of the three isoforms. These results indicate that four days of treatment with moderate to high doses of SJW, hyperforin or hypericin fails to induce these CYP450 isoforms in the male Swiss Webster mouse.

Topics: Alanine Transaminase; Animals; Anthracenes; Antidepressive Agents; Body Weight; Bridged Bicyclo Compounds; Cytochrome P-450 Enzyme System; Enzyme Induction; Hypericum; Isoenzymes; Liver; Male; Mice; Perylene; Phloroglucinol; Plant Preparations; Terpenes

Our purpose was to determine whether prenatal exposure to the herb hypericum (St John's wort) affects long-term growth and physical maturation of mouse offspring.. Forty CD-1 mice were randomly assigned to receive daily doses of either 180 mg/kg per day hypericum (n = 20) or a placebo (n = 20) for 2 weeks before conception and throughout gestation. Perinatal outcomes, growth, and physical milestones of the offspring were compared in a blinded manner. Variables were compared by analysis of variance or by chi2 testing.. The gestational ages at delivery and litter sizes did not differ between the hypericum-exposed and the placebo-exposed offspring. The body weight, body length, and head circumference measurements from postnatal day 3 through adulthood increased in a manner that was indistinguishable between the two groups of offspring, regardless of gender. No differences in reaching physical milestones (teeth eruptions, eye opening, external genitalia) were noted between the 2 groups. The reproductive capability, perinatal outcomes, and growth and development of the second-generation offspring were unaffected by hypericum exposure.. Maternal administration of hypericum before and throughout gestation did not affect long-term growth and physical maturation of exposed mouse offspring.

Topics: Animals; Biometry; Body Weight; Cephalometry; Depression; Female; Genitalia; Gestational Age; Growth; Hypericum; Male; Mice; Plant Extracts; Plants, Medicinal; Pregnancy; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Reproduction; Tooth Eruption

Increasing widespread use of St. John's Wort (SJW, Hypericum perforatum) has led to concerns about its use in pregnant women. Behavioral and physiological alterations resulting from developmental treatment were investigated in Sprague-Dawley rats exposed to diets containing 0, 180, 900, 1800 or 4500ppm SJW beginning on gestational day 3 and ending at offspring weaning on postnatal day (PND) 21. These dietary doses span 1-25 times the recommended human dose. Post-weaning behavioral assessments of male and female offspring included: open field activity, acoustic startle, performance of complex and Morris water mazes, and activity in an elevated plus-maze. There were no SJW effects on maternal weight gain or duration of gestation; offspring body weights were similar to controls from PND 2 through PND 56 after which, some treated groups weighed significantly less than the controls. There were no SJW-related behavioral alterations on any measure. Whole and regional brain weights of offspring at adulthood indicated no significant effects of SJW. These results indicate that there are few neurobehavioral alterations resulting from developmental SJW treatment in rats.

Topics: Animals; Body Weight; Brain; Dose-Response Relationship, Drug; Female; Humans; Hypericum; Male; Maze Learning; Models, Animal; Motor Activity; Organ Size; Plant Preparations; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Reflex, Startle; Weaning