Perforatum Extract Research Articles

Serotonin mediates beneficial effects of Hypericum perforatum on nicotine withdrawal signs

Antidepressants may be effective treatment for smoking cessation and new evidence on relationship between smoking and depression is emerging. Extracts of the plant Hypericum perforatum possess antidepressant activity in humans and reduce nicotine withdrawal signs in mice. Both nicotine and H. perforatum administration elicit changes in serotonin (5-HT) formation in the brain. On this basis, we investigated the possible involvement of 5-HT in the beneficial effects of H. perforatum on nicotine withdrawal signs. With the aim to induce nicotine dependence, nicotine (2 mg/kg, four intraperitoneal injections daily) was administered for 14 days to mice (NM). Saline (controls, M) or H. perforatum extract (Ph 50, 500 mg/kg) were orally administered immediately after the last nicotine injection for 30 days after nicotine withdrawal. Another group of animals treated with nicotine (14 days) and successively with H. perforatum extract was intraperitoneally co-administered with selective 5-HT receptorial antagonist WAY 100635 (WAY) (1 mg/kg). All animals were evaluated for locomotor activity and abstinence signs, 24 after nicotine withdrawal. Brain 5-HT metabolism was evaluated in the cortex of mice sacrificed 30 days after nicotine withdrawal through evaluation of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/5-HT ratio. After nicotine withdrawal measurement of 5-HT metabolism in the cortex showed a reduction of 5-HT content while animals treated only with Hypericum extract showed a significant reduction of total abstinence score compared to controls. WAY inhibited the reduction of total abstinence score induced by H. perforatum. Moreover, 5-HT1A expression has been evaluated 30 days after nicotine withdrawal. Our results, show a significant increase of cortical 5-HT content in NM treated with H. perforatum, with a concomitant significant increase of 5-HT1A receptor. So, it is possible to suggest an involvement of 5-HT in beneficial effects of H. perforatum on suffering produced by nicotine withdrawal in dependent mice.

Influence of Hypericum perforatum extract and its single compounds on amyloid-β mediated toxicity in microglial cells

As immunocompetent cells of the brain, microglia are able to counteract the damaging effects of amyloid-β in Alzheimer's disease by phagocytosis-mediated clearance of protein aggregates. The survival and health of microglia are therefore critical for attenuating and preventing neurodegenerative diseases. In a microglial cell line pretreated with St. John's wort ( Hypericum perforatum L.) extract (HPE), the cell death evoked by treatment with amyloid-β (25–35) and (1–40) was attenuated significantly in a dose-dependent manner. Investigation of the single compounds in the extract revealed that the flavanols (+)-catechin and (−)-epicatechin increase cell viability slightly, whereas the flavonol quercetin and its glycosides rutin, hyperosid and quercitrin showed no effect on cell viability. In contrast, at the same concentration, the flavonoids reduced the formation of amyloid-induced reactive oxygen species in microglia, indicating that improvement of cell viability by the catechins is not correlated to the antioxidant activity. No influence of HPE on the capacity of microglia to phagocytose sub-toxic concentrations of fibrillar amyloid-β (1–40) was observed. Other experiments showed that HPE, (+)-catechin and (−)-epicatechin can alter cellular membrane fluidity and thereby may have a beneficial effect on cell health. Our findings provide in vitro evidence that treatment especially with the complex plant extract HPE may restore or improve microglial viability and thereby attenuate amyloid-β mediated toxicity in Alzheimer's disease.

Placebo controlled continuation treatment with Hypericum extract WS® 5570 after recovery from a mild or moderate depressive episode

Patients suffering from an acute episode of mild to moderate major depression and who had been treated successfully with Hypericum perforatum extract WS 5570 in doses of 600 mg/day or 1200 mg/day or with placebo for 6 weeks in a multi-centre, double-blind, randomized clinical trial, were asked to take part in a continuation treatment. Those participants with a HAMD total score decrease > or =50% during acute treatment were eligible for 4 months of double-blind continuation treatment with the same dose regimen. In total, 69, 68 and 24 (WS 5570 600 mg/day, 1200 mg/day and placebo) patients entered continuation treatment. Both WS 5570 groups showed an additional slight decrease of the HAMD total score by 0.8 (600 mg WS 5570/day) and 0.4 (1200 mg WS 5570/day) points during treatment phase, while patients in the placebo group deteriorated by 2.1 points. The incidence of adverse events was low in all therapy groups.

Simultaneous determination of total hypericin and hyperforin in St. John's wort extracts by HPLC with electrochemical detection

An analytical procedure was developed for the simultaneous determination of total hypericin (protopseudohypericin, pseudohypericin, protohypericin and hypericin) and hyperforin in Hypericum perforatum (St. John's wort) extracts and its preparations. The determination of total hypericin and hyperforin in one step was achieved by exposing the samples to artificial daylight in amber glass vials. This procedure allows both the photoconversion of the protoforms into the appropriate hypericins and the protection of the photosensitive hyperforin. For quantification, an HPLC method with electrochemical detection was applied. As an example of the application of the principle, two preparations containing St. John's wort were assayed.

Phloroglucinol Derivatives from Two Mediterranean Hypericum L. (Clusiaceae) Species

The flowering plant genus Hypericum L. (St. John's Wort, Clusiaceae) is the subject of considerable interest due to the use of H. perforatum extracts as treatment for mild to moderate depression. Extensive phytochemical and pharmacological research on this species has revealed many bioactive substances, including flavonoid glycosides, naphthodianthrones (hypericin) and phloroglucinol derivatives (hyperforin) [1]. The latter class of substances is interesting both chemically and pharmacologically [2]. As part of our continuing research on phytochemistry of the genus Hypericum, two species – H. polyphyllum Boiss. & Balansa (section Olympia) and H. empetrifolium Willd. (section Coridium) – occurring in Mediterranean region were phytochemically studied. A phloroglucinol derivative (1) previously isolated from H. jovis and H. stypheloides was isolated from the DCM extract of H. empetrifolium fruits. Two new flavones, one major (2) and one minor one, were isolated from the DCM extract of H. polyphyllum fruits.

St. John's Wort (Hypericum perforatum L.,Clusiaceae) polysaccharides affect the signal transduction of human skin keratinocytes and fibroblasts

The traditional dermatological use of Hypericum perforatum L., Clusiaceae, extracts is currently undergoing a renaissance and a potential use in treatment of topic dermatitis is discussed. Since the use of H. perforatum extracts for topical treatment of skin diseases like atopic dermatitis has been discussed, the intention of the present study was to determine the most active polysaccharide fraction of the crude extract influencing keratinocytes and even fibroblasts. The crude polysaccharide fraction was fractionated by anion exchange chromatography (AEC) with regard to the polymer acidity followed by treatment of skin cells with 10µg/ml of each obtained polysaccharide. qRT-PCR studies elucidated the influence of polysaccharides on the expression of proliferation (EGF-R, FGF2-R, InsR, STAT6, FGF-7) and differentiation (PKC-α, SMAD3) related genes. The crude polysaccharide of St. John wort water extract induced the differentiation as measured by involucrin and keratin K1 and K10 content, while no effects on proliferation were observed. In the case of the AEC, fractions the two most acidic polysaccharides revealed a very strong effect on keratinocyte differentiation examined morphologically as well as by determination of involucrin. Gene expression analysis demonstrated that the PKC-α gene was the preferred up-regulated gene in keratinocytes. The effect on primary fibroblasts was different: Mitochondrial activity as well as proliferation was enhanced. Examination of proliferation specific genes showed that the EGF-R, STAT6 and FGF-7genes were up-regulated as compared to the untreated control cells. Apoptotic and necrotic cells were not observed after treatment of skin cells with St. John wort polysaccharides. In conclusion it could be shown that the acidic polysaccharides exert the greatest influence on keratinocyte differentiation and that their influence on epidermal keratinocytes differs from their effect on dermal fibroblasts.

Identification of the major constituents of Hypericum perforatum by LC/SPE/NMR and/or LC/MS

The newly established hyphenated instrumentation of LC/DAD/SPE/NMR and LC/UV/(ESI)MS techniques have been applied for separation and structure verification of the major known constituents present in Greek Hypericum perforatum extracts. The chromatographic separation was performed on a C18 column. Acetonitrile-water was used as a mobile phase. For the on-line NMR detection, the analytes eluted from column were trapped one by one onto separate SPE cartridges, and hereafter transported into the NMR flow-cell. LC/DAD/SPE/NMR and LC/UV/MS allowed the characterization of constituents of Greek H. perforatum, mainly naphtodianthrones (hypericin, pseudohypericin, protohypericin, protopseudohypericin), phloroglucinols (hyperforin, adhyperforin), flavonoids (quercetin, quercitrin, isoquercitrin, hyperoside, astilbin, miquelianin, I3,II8-biapigenin) and phenolic acids (chlorogenic acid, 3- O-coumaroylquinic acid). Two phloroglucinols (hyperfirin and adhyperfirin) were detected for the first time, which have been previously reported to be precursors in the biosynthesis of hyperforin and adhyperforin.

Wound-healing activity of St. John's Wort ( Hypericum perforatum L.) on chicken embryonic fibroblasts

Wound-healing effect of St. John's Wort ( Hypericum perforatum L.) extract was evaluated by comparing with dexpanthenol and titrated extract of Centella asiatica (TECA) on cultured chicken embryonic fibroblasts. Chicken embryonic fibroblasts from fertilized eggs were incubated with the plant extract, dexpanthenol and TECA. Using microscopical methods by staining cells, mitotic ability, morphologic changes and collagen production in the cultured fibroblasts were evaluated as parameters to approach its mechanism of action in wound repair. Findings obtained in the present study indicated that Hypericum perforatum extract exhibited a wound-healing activity whose mechanism of action is similar to that of TECA. Wound-healing activity of Hypericum perforatum extract seems to be mainly due to the increase in the stimulation of fibroblast collagen production and the activation of fibroblast cells in polygonal shape, which plays a role in wound repair by closing damaged area. The findings demonstrated the wound-healing activity of Hypericum perforatum, which has previously been based on ethnomedical data.

Effects of acute and repeated administration of Hypericum perforatum extract (WS 5572®) and its main constituents on extracellular levels of serotonin, noradrenaline and dopamine in the rat brain: A microdialysis study

Effects of acute and repeated administration of Hypericum perforatum extract (WS 5572®) and its main constituents on extracellular levels of serotonin, noradrenaline and dopamine in the rat brain: A microdialysis study

Mass spectral characterization of phloroglucinol derivatives hyperforin and adhyperforin

Active phloroglucinol constituents of Hypericum perforatum (St. John's wort) extracts, hyperforin and adhyperforin, have been studied following ion activation using tandem mass spectrometry (MS/MS) and complemented by accurate mass measurements. These two compounds were readily analyzed as protonated and deprotonated molecules with electrospray ionization. MS/MS and MS3 data from a quadrupole-linear ion trap tandem mass spectrometer were employed to elucidate fragmentation pathways. Fourier transform ion cyclotron resonance measurements afforded excellent mass accuracies for the confirmation of elemental formulae of product ions formed via infrared multiphoton dissociation and sustained off-resonance irradiation collision-induced dissociation. Fragmentation schemes have been devised for the dissociation of hyperforin and adhyperforin in negative and positive ion modes. This information is expected to be especially valuable for the characterization of related compounds, such as degradation products, metabolites and novel synthetic analogs of hyperforin.

Enhanced neuroprotective effect by combination of bromocriptine and Hypericum perforatum extract against MPTP-induced neurotoxicity in mice

The present study has been designed to evaluate the combined effect of bromocriptine (BRC) and Hypericum perforatum extract (HPE) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease in male Swiss Albino mice, which were randomly divided into seven groups of six animals each. Group I served as control. Groups II and III were given 300 mg/kg HPE (po) and 10 mg/kg BRC (i.p.) respectively, once daily for 7 days. The four doses of MPTP (20 mg/kg) were administered intraperitoneally with an interval of 2 h to the groups IV, V, VI and VII. The drug treatment was given to fifth group (10 mg/kg BRC; i.p), sixth group (300 mg/kg HPE; po) and seventh group (300 mg/kg HPE; po and 10 mg/kg BRC; i.p.) once in a day for 7 days and the dose on the first day was given 30 min prior to first MPTP injection. The rotarod test, hang test and forepaw stride length revealed significant improvement by the combined treatment. Dopamine and DOPAC levels were significantly improved ( p < 0.05). There was a significant reduction in lipid peroxidation after the combined treatment ( p < 0.05) and the antioxidant status was improved. These findings suggest that the combined effect of BRC and HPE was more pronounced than BRC or HPE alone. So it is concluded that the combined treatment might be preferable to either BRC (or) HPE alone in the effective clinical management of Parkinson's disease.

Reduction in hypericin-induced phototoxicity by Hypericum perforatum extracts and pure compounds

Clinical evidence suggests that administration of Hypericum perforatum (Hp) extracts containing the photo-activated hypericin compounds may cause fewer skin photosensitization reactions than administration of pure hypericin. This study was conducted to determine whether the phototoxicity of hypericin in HaCaT keratinocytes could be attenuated by H. perforatum extracts and constituents. Two extracts, when supplemented with 20 μM hypericin: (1) an ethanol re-extraction of residue following a chloroform extraction (denoted ethanol(-chloroform)) (3.35 μM hypericin and 124.0 μM total flavonoids); and (2) a chloroform extract (hypericin and flavonoids not detected), showed 25% and 50% ( p < 0.0001) less phototoxicity than 20 μM hypericin alone. Two H. perforatum constituents, when supplemented with 20 μM hypericin: (1) 10 μM chlorogenic acid; and (2) 0.25 μM pyropheophorbide, exhibited 24% ( p < 0.05) and 40% ( p < 0.05) less phototoxicity than 20 μM hypericin alone. The peroxidation of arachidonic acid was assessed as a measure of oxidative damage by photo-activated hypericin, but this parameter of lipid peroxidation was not influenced by the extracts or constituents. However α-tocopherol, a known antioxidant also did not influence the amount of lipid peroxidation induced in this system. These observations indicate that hypericin combined with H. perforatum extracts or constituents may exert less phototoxicity than pure hypericin, but possibly not through a reduction in arachidonic acid peroxidation.

Superior efficacy of St John's wort extract WS®5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298

BackgroundThe aim of the current study was to assess the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort) extract WS® 5570 at doses of 600 mg/day in a single dose and 1200 mg/day in two doses.MethodsThe participants in this double-blind, randomized, placebo-controlled, multi-center clinical trial were male and female adult out-patients with an episode of mild or moderate major depressive episode (single or recurrent episode, DSM-IV criteria). As specified by the relevant guideline, the study was preceded by a medication-free run-in phase. For the 6-week treatment, 332 patients were randomized: 123 to WS® 5570 600 mg/day, 127 to WS® 5570 1200 mg/day, and 82 to placebo. The primary outcome measure was the change in total score on the Hamilton Rating Scale for Depression (HAM-D, 17-item version) between baseline and endpoint. Additional measures included the number of responders, the number of patients in remission, and several other standard rating scales. Efficacy and safety were assessed after 2 and 6 weeks. The design included an interim analysis performed after randomization with the option of early termination.ResultsAfter 6 weeks of treatment, mean ± standard deviation decreases in HAM-D total scores of 11.6 ± 6.4, 10.8 ± 7.3, and 6.0 ± 8.1 points were observed for the WS® 5570 600 mg/day, 1200 mg/day and placebo groups, respectively (endpoint analysis). Secondary measures of treatment efficacy also showed that both WS® 5570 groups were statistically superior to placebo. Significantly more patients in the WS® 5570 treatment groups than in the placebo group showed treatment response and remission. WS® 5570 was consistently more effective than placebo in patients with either less severe or more severe baseline impairment. The number of patients who experienced remission was higher in the WS® 5570 1200 mg/day group than the WS® 5570 600 mg/day group. The incidence of adverse events was low in all groups. The adverse event profile was consistent with the known profile for Hypericum extract preparations.ConclusionHypericum perforatum extract WS® 5570 at doses of 600 mg/day (once daily) and 1200 mg/day (600 mg twice daily) were found to be safe and more effective than placebo, with comparable efficacy of the WS® 5570 groups for the treatment of mild to moderate major depression.

Attenuation of ethanol withdrawal syndrome by extract of Hypericum perforatum in Wistar rats

The effects of Hypericum perforatum (St John's wort) on ethanol withdrawal syndrome have been investigated in ethanol-dependent rats. Adult male Wistar rats were subjects. Ethanol (7.2% v/v) was given to rats by a liquid diet for 15 days. Hypericum perforatum extract (HPE) (25-200 mg/kg) and saline were injected to rats intraperitoneally just before ethanol withdrawal. After second, fourth and sixth hour of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, stereotyped behavior and tremors were recorded or rated. A second series of injections was given at 6 h after the first one, and subjects were then tested for audiogenic seizures. HPE (25-200 mg/kg) produced some dose-dependent and significant inhibitory effects on locomotor hyperactivity at second and sixth hour of ethanol withdrawal. In addition, it significantly reduced the number of stereotyped behaviors at the same dose range. HPE (50 and 100 mg/kg) produced some significant inhibitory effects on tremor and audiogenic seizures during withdrawal period. These results suggest that HPE has some beneficial effects on ethanol withdrawal syndrome in rats.

Protective effect of Hypericum perforatum in zymosan-induced multiple organ dysfunction syndrome: Relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity

Hypericum perforatum is a medicinal plant species containing many polyphenolic compounds, namely flavonoids and phenolic acids. Since polyphenolic compounds have high antioxidant potential, we have investigated the effects of H. perforatum extract on the development of multiple organ dysfunction syndrome caused by zymosan (500 mg/kg, administered i.p. as a suspension in saline) in mice. Organ failure and systemic inflammation in rats was assessed 18 h after administration of zymosan and/or H. perforatum extract and monitored for 12 days (for loss of body weight and mortality). Treatment of mice with H. perforatum extract (30 mg/kg i.p., 1 and 6 h after zymosan) attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan, pulmonary, intestinal and pancreatic injury, and renal dysfunction as well as the increase in myeloperoxidase in the lung and intestine. Immunohistochemical analysis for inducible nitric oxide synthase (iNOS), nitrotyrosine, and poly(ADP-ribose) (PAR) revealed positive staining in lung and intestine tissues obtained from zymosan-injected mice. The degree of staining for nitrotyrosine, iNOS, and PAR was markedly reduced in tissue sections obtained from zymosan-treated mice, which received H. perforatum extract. In conclusion, this study provides evidence, for the first time, that H. perforatum extract attenuates the degree of zymosan-induced multiple organ dysfunction syndrome in mice.

A radioassay for synaptic core complex assembly: Screening of herbal extracts for effectors

Synaptic core complex formation between syntaxin and synaptosome-associated protein of 25 kDa (SNAP25) on the plasma membrane and synaptobrevin on the vesicle membrane is responsible for membrane fusion and neurotransmitter release. A radiolabeled protein binding assay for synaptic core complex formation was developed. The components of this assay included recombinant glutathione S-transferase (GST)–syntaxin immobilized on glutathione agarose beads, SNAP25 and 125I-labeled synaptobrevin. Reactions were performed in tubes containing filter inserts to facilitate removal of unbound protein. The radiolabeled protein bound was then quantified by gamma counter. A K d of 1.6 μM was determined for the GST–syntaxin/SNAP25/synaptobrevin complex, and a K d of 12 μM was determined for the GST–syntaxin/synaptobrevin complex. The assay was used to screen 14 herbal extracts for effectors of core complex formation. Herbs traditionally used to treat neurological conditions such as depression, anxiety, and stress were chosen. A Hypericum perforatum extract was found to have a nonspecific effect via protein complexation, whereas an Albizzia julibrissin extract was found to reduce the level of core complex formation. The assay was used to further investigate the effect of the A. julibrissin extract. The discovery of an inhibitor of core complex formation demonstrates the efficacy of the assay in screening natural products for substances that affect core complex formation.

NEUROPROTECTION AND ENHANCED RECOVERY WITH HYPERICUM PERFORATUM EXTRACT AFTER EXPERIMENTAL SPINAL CORD INJURY IN MICE

Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants, and/or a depletion of antioxidants. A considerable body of recent evidence suggests that oxidative stress and exaggerated production of reactive oxygen species play a major role in several aspects of inflammation. Hypericum perforatum is a medicinal plant species containing many polyphenolic compounds, namely, flavonoids and phenolic acids. Because polyphenolic compounds have high antioxidant potential, in this study, we evaluated the effect of H. perforatum (given at 30 mg . kg (-1)) in an experimental animal model of spinal cord injury, which was induced by the application of vascular clips to the dura via a four-level T5 through T8 laminectomy. The degree of (a) spinal cord inflammation and tissue injury (histological score), (b) nitrotyrosine, (c) poly(adenosine diphosphate-ribose), (d) neutrophils infiltration, and (e) the activation of signal transducer and activator transcription 3 was markedly reduced in spinal cord tissue obtained from H. perforatum extract-treated mice. We have also demonstrated that H. perforatum extract significantly ameliorated the recovery of limb function.

PGE2 as a measure of anti‐inflammatory activity in Hypericum perforatum extracts and pure constituents

Recent reports provide evidence that Hypericum perforatum (Hp) may possess anti-inflammatory properties. We assessed the anti-inflammatory activity of extracts and constituents using RAW264.7 macrophage cells stimulated with lipopolysaccharide (LPS) and prostaglandin E2 (PGE2) was measured after 8 hours. Extracts made from commercial source Frontier Herb exhibited reductions in PGE2 regardless of extraction procedure used; Iowa State Plant Introduction Station material revealed that only certain soxhlet chloroform extractions reduced PGE2. Of the flavonoids, rutin showed no reduction in PGE2 at concentrations up to 20 uM, quercetin showed a reduction in PGE2 at 5 uM (p=.0001) and a potent reduction in PGE2 from 10 to 40 uM (p<.0001) while quercetrin showed a reduction in PGE2 at 20 uM (p=.0197). The phloroglucinol hyperforin showed a reduction in PGE2 at 2 uM (p=.0297). The napthodianthrones hypericin (2 uM and 5 uM) and pseudohypericin (0.5 uM and 2 uM) showed no effect on PGE2 levels when assayed in the dark; light-activated hypericin showed no effect on PGE2; but 2 uM light-activated pseudohypericin showed a reduction in PGE2 (p<.0119). There was a significant increase in PGE2 production of 2 uM and 5 uM hypericin without LPS in light-activated versus dark conditions, warranting further study of the napthodianthrones’ effect on inflammation. Future work includes isolating and identifying constituents responsible for activity, but it is likely interactions of compounds accounting for the anti-inflammatory activity of extracts. Supported by grant ES012020 from NIEHS and ODS, NIH.

Black Cohosh and St. John’s Wort for Climacteric Complaints

To investigate the efficacy of the fixed combination of black cohosh (Cimicifuga racemosa) and St. John's wort (Hypericum perforatum) extracts in women with climacteric complaints with a pronounced psychological component. In this double-blind randomized placebo-control study, 301 women experiencing climacteric complaints with psychological symptoms were treated with ethanolic St. John's wort extract and isopropanolic black cohosh extract or a matched placebo for 16 weeks. Climacteric complaints were evaluated by means of the Menopause Rating Scale mean score, and psychological complaints were evaluated using the Hamilton Depression Rating Scale sum score. The mean (+/- standard deviation) Menopause Rating Scale score decreased 50% (0.46 +/- 0.13 to 0.23 +/- 0.13) in the treatment group and 19.6% (0.46 +/- 0.14 to 0.37 +/- 0.15) in the placebo group. The Hamilton Depression Rating Scale total score decreased 41.8% in the treatment group (18.9 +/- 2.2 to 11.0 +/- 3.8 points), and 12.7% in the placebo group (18.9 +/- 2.1 to 16.5 +/- 4.3). The treatment was significantly (P < .001) superior to placebo in both measures. There were no relevant group differences regarding adverse events, laboratory values, or tolerability. This fixed combination of black cohosh and St. John's wort is superior to placebo in alleviating climacteric complaints, including the related psychological component. I.

HYPERICUM PERFORATUM ATTENUATES THE DEVELOPMENT OF CERULEIN-INDUCED ACUTE PANCREATITIS IN MICE

A considerable body of recent evidence suggests that oxidative stress and exaggerated production of reactive oxygen species play a major role in several aspects of inflammation and shock. Hypericum perforatum is a medicinal plant species containing many polyphenolic compounds, namely flavonoids and phenolic acids. Because polyphenolic compounds have high antioxidant potential, in this study we evaluated the effect of Hypericum perforatum extract on acute pancreatitis induced by cerulein administration in male CD mice. Intraperitoneal injection of cerulein in mice resulted in a severe, acute pancreatitis, which was characterized by edema, neutrophil infiltration, tissue hemorrhage, and cell necrosis as well as increases in the serum levels of amylase and/or lipase in comparison to sham-treated mice. The infiltration of the pancreatic tissue of these animals with neutrophils (measured as increase in myeloperoxidase activity) was associated with expression of the adhesion molecule ICAM-1. Immunohistochemical examination demonstrated a marked increase in the staining (immunoreactivity) for nitrotyrosine and poly(ADP-ribose) (PAR) in the pancreas of cerulein-treated mice in comparison to sham-treated mice. In contrast, the degree of (a) pancreatic inflammation and tissue injury (histological score), (b) expression of ICAM-1, (c) the staining for nitrotyrosine and PAR, and (d) myeloperoxidase activity was markedly reduced in pancreatic tissue sections obtained from cerulein-treated mice administered Hypericum perforatum extract (30 mg/kg, suspended in 0.2 mL of saline solution, o.s.). Moreover, the treatment with Hypericum perforatum extract significantly reduced the mortality rate at 5 days after cerulein administration. Taken together, our results indicate that Hypericum perforatum extract reduces the development of acute pancreatitis.