hypericum and Pain

Hypericum perforatum L. (Hypericaceae), popularly called St. John's wort (SJW), has a rich historical background being one of the oldest used and most extensively investigated medicinal herbs. Many bioactivities and applications of SJW are listed in popular and in scientific literature, including antibacterial, antiviral, anti-inflammatory. In the last three decades many studies focused on the antidepressant activity of SJW extracts. However, several studies in recent years also described the antinociceptive and analgesic properties of SJW that validate the traditional uses of the plant in pain conditions.. This review provides up-to-date information on the traditional uses, pre-clinical and clinical evidence on the pain relieving activity of SJW and its active ingredients, and focuses on the possible exploitation of this plant for the management of pain.. Historical ethnobotanical publications from 1597 were reviewed for finding local and traditional uses. The relevant data on the preclinical and clinical effects of SJW were searched using various databases such as PubMed, Science Direct, Scopus, and Google Scholar. Plant taxonomy was validated by the database Plantlist.org.. Preclinical animal studies demonstrated the ability of low doses of SJW dry extracts (0.3% hypericins; 3-5% hyperforins) to induce antinociception, to relieve from acute and chronic hyperalgesic states and to augment opioid analgesia. Clinical studies (homeopathic remedies, dry extracts) highlighted dental pain conditions as a promising SJW application. In vivo and in vitro studies showed that the main components responsible for the pain relieving activity are hyperforin and hypericin. SJW analgesia appears at low doses (5-100mg/kg), minimizing the risk of herbal-drug interactions produced by hyperforin, a potent inducer of CYP enzymes.. Preclinical studies indicate a potential use of SJW in medical pain management. However, clinical research in this field is still scarce and the few studies available on chronic pain produced negative results. Prospective randomized controlled clinical trials performed at low doses are needed to validate its potential efficacy in humans.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antidepressive Agents; Clinical Trials as Topic; Depression; Humans; Hypericum; Pain; Plant Extracts

This review aims at a coherent summary of the results obtained from various studies that concern analgesic-like activity of the extracts of H. preforatum L and thirteen other Hypericum L. species (Hypericaceae). Botanical origin, plant organs and extraction modes of the plant material, experimental models, routes of administration and doses used for animal treatment are summarized. Mechanisms of action and substances (and even the synergy thereof) proposed so far to be responsible for the observed activity have also been discussed. Even though St. John's wort (H. perforatum) is the most renowned plant species of this genus, it is neither the only nor the most potent one in inducing pain relief.

Topics: Analgesics; Hypericum; Pain; Plant Extracts

Hypericum perforatum (St. John's Wort) has been used for a variety of medicinal indications. Most recent research has focussed on its use in herbal form for depression, but its claimed analgesic and anti-inflammatory properties in homeopathic form have also led to a number of studies in patients with acute pain conditions. This systematic review overviews the literature on the use of St. John's Wort for pain conditions in homeopathic dental practice.. PubMed, EMBASE, AMED, CAMbase and the electronic archives of Thieme Publishers were searched with the search terms "(Hypericum OR St. Johns Wort) AND pain". We reviewed and meta-analysed the evidence on Hypericum in pain after tooth extraction was carried out.. Twenty one relevant articles were found: four described general recommendations, three basic research, six reported studies in dental care and eight were expert opinions or case reports. Four studies were eligible for the meta-analysis. There was marked high heterogeneity in the effects pain (Chi-Squared = 26.46; I(2) = 0.89). The overall effect of 0.24 (95% CI: [0.06; 1.03]) favours Hypericum but is not statistically significant.. Although case reports suggest therapeutic potential of Hypericum for pain conditions in dental care, this effect is not currently supported by clinical studies. All studies included in this meta-analysis used Arnica montana as well as Hypericum the results are more influenced by Arnica than Hypericum. Further clinical controlled trials of Hypericum alone in dental practice should be performed.

Topics: Dental Anxiety; Dental Care; Homeopathy; Humans; Hypericum; Pain; Phytotherapy; Plant Extracts

In this work, previously published and unpublished results on biological activity of Hypericum caprifoliatum, a native species to South Brazil, are presented. Lipophilic extracts obtained from this species showed an antidepressant-like activity in mice and rat forced swimming test. Results from in vivo experiments suggest an effect on the dopaminergic transmission. Besides that, in vitro experiments demonstrated that the extract and its main component (a phloroglucinol derivative) inhibit monoamine uptake in a concentration-dependent manner, more potently to dopamine, but this effect is not related to direct binding at the uptake sites. It was also observed that a 3-day treatment with lipophilic extract prevents stress-induced corticosterone rise in mice frontal cortex but not in plasma. The lipophilic and methanolic H. caprifoliatum extracts also demonstrated antinociceptive effect, which seems to be indirectly mediated by the opioid system. These results indicate that H. caprifoliatum presents a promising antidepressant-like effect in rodents which seems to be related to a mechanism different from that of other classes of antidepressants.

Topics: Animals; Antidepressive Agents; Anxiety; Brazil; Depression; Hypericum; Pain; Plant Extracts; Rodentia; Seizures

To evaluate the clinical efficacy of a hypericum and neem oil dressing, Primary Wound Dressing [ONE] (1PWD) (Kerecis AG, Switzerland), in a patient population with dehiscence of surgical wounds with critical colonisation/infection. Efficacy was defined as resolution of inflammatory/infective symptoms.. A randomised, controlled, single-blinded, parallel-arms phase III study was conducted comparing the experimental medication to silver-based dressings. All patients were evaluated at enrolment, on days 7, 14, 21 and 28. Improvement of inflammatory/infective symptoms was measured by detecting seven items of the Bates-Jensen Wound Assessment Tool (BWAT). Pain was assessed using the Numeric Rating Scale (NRS).. The study enrolled 99 patients. Follow-up was completed in 49 patients in the experimental group and 48 patients in the control group. Overall BWAT evaluation demonstrated similar outcomes between the groups: t=0.23, p-value=0.81, 95% confidence interval (CI): -13.3-10.8. Furthermore, when evaluating the seven items of the BWAT relating to inflammatory signs, there was not a significant difference between the groups: t=0.38, p=0.35, 95% CI: -2.8-2.7. However, when an analysis using the NRS pain scale was performed, a statistically significant pain reduction was demonstrated in favour of the experimental group: t=7.8, p<0.0001, 95% CI: 2.918-4.8819.. This randomised controlled trial confirmed the efficacy of 1PWD, an investigational product, in the management of surgical dehiscence with critical colonisation or infection, with the added benefit of significant pain reduction when compared with a silver-based dressing.

Topics: Glycerides; Humans; Hypericum; Pain; Silver; Surgical Wound; Surgical Wound Infection; Terpenes; Wound Healing

To determine the efficacy and tolerance of Otikon Otic Solution (Healthy-On Ltd, Petach-Tikva, Israel), a naturopathic herbal extract (containing Allium sativum, Verbascum thapsus, Calendula flores, and Hypericum perforatum in olive oil), compared with Anaesthetic (Vitamed Pharmaceutical Ltd, Benyamina, Israel) ear drops (containing ametocaine and phenazone in glycerin) in the management of ear pain associated with acute otitis media (AOM).. Children between the ages of 6 and 18 years who experienced ear pain (otalgia) and who were diagnosed with eardrum problems associated with AOM were randomly assigned to be treated with Otikon or Anaesthetic ear drops, which were instilled into the external canal(s) of the affected ear(s). Ear pain was assessed using 2 visual analog scales: a linear scale and a color scale. Pain assessment took place throughout the course of 3 days. The mean score of pain reduction was used to measure outcome.. Primary pediatric community ambulatory centers.. One hundred three children aged 6 to 18 years who were diagnosed with otalgia associated with AOM.. Each of the 2 treatment groups were comparable on the basis of age, sex, laterality of AOM, and the effectiveness of ameliorating symptoms of otalgia. The 2 groups were also comparable to each other in the initial ear pain score and in the scores at each application of Otikon or Anaesthetic drops. There was a statistically significant improvement in ear pain score throughout the course of the study period (P =.007).. Otikon, an ear drop formulation of naturopathic origin, is as effective as Anaesthetic ear drops and was proven appropriate for the management of AOM-associated ear pain.

Topics: Adolescent; Ambulatory Care; Analgesics; Child; Complementary Therapies; Female; Garlic; Humans; Hypericum; Male; Otitis Media; Pain; Pain Measurement; Phytotherapy; Plant Extracts; Plants, Medicinal; Treatment Outcome

The south Brazilian Hypericum species have revealed the presence of a series of biologically active phloroglucinol derivatives. In this study, a mixture of japonicine A and an isomer with an unreported structure, named japonicine E, was isolated from the roots of H. polyanthemum. Additionally, uliginosin A from H. myrianthum, isouliginosin B from H. polyanthemum, hyperbrasilol B and isohyperbrasilol B from H. caprifoliatum and cariphenone A from H. carinatum were also isolated. The structures were elucidated using 1D- and 2D-NMR experiments and by comparison with previously reported data. The compounds japonicines A/E, uliginosin A, isouliginosin B, hyperbrasilol B and cariphenone A exhibited antinociceptive activity in the mice hot-plate test and did not induce motor impairment in the rotarod apparatus.

Topics: Analgesics; Animals; Brazil; Dose-Response Relationship, Drug; Hypericum; Male; Mice; Mice, Inbred Strains; Molecular Structure; Pain; Pain Measurement; Phloroglucinol; Plant Roots

The present therapeutic agents for the treatment of pain, inflammation and pyrexia are not very effective and accompanied by various side effects. Therefore, new effective agents are the most wanted. The present study investigates the anti-nociceptive, anti-inflammatory and antipyretic activities of crude methanol extract of Hypericum oblongifolium.. In vivo acetic acid induced writhing and hot plate tests were used for antinociceptive effects at 100, 200 and 300 mg/kg i.p. The anti-inflammatory and antipyretic potential of methanol extract were tested in carrageenan induced paw edema in mice and yeast induced hyperthermia respectively.. The extract doses of 100, 200 and 300 mg/kg i.p. revealed significant inhibitory effect (P < 0.001) in acetic acid induced writhing test. Pretreatment of extract at doses of 100, 200 and 300 mg/kg i.p. produced significant anti-inflammatory effect (P < 0.001) in the carrageenan induced paw edema. The methanol extract also showed significant antipyretic effect in yeast induced hyperthermia in mice during various assessment times.. The methanol extract of H. oblongifolium showed significant anti-nociceptive, anti-inflammatory and antipyretic effects in various animal models and thus validates the traditional uses of the plant in said conditions.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Female; Fever; Hypericum; Inflammation; Male; Mice; Mice, Inbred BALB C; Pain; Phytotherapy; Plant Extracts; Plants, Medicinal

Investigate the involvement of monoaminergic and glutamatergic systems on the antinociceptive and ataxic effects of uliginosin B, which we have already demonstrated to be a promising molecular scaffold to develop new analgesic drugs.. Uliginosin B was obtained from hexane extract of aerial parts of Hypericum polyanthemum by chromatographic methods. Uliginosin B antinociceptive and motor coordination effects were evaluated in mice by using hot-plate (15 and 90 mg/kg, i.p.) and rotarod (90 mg/kg, i.p.) tests, respectively. The mechanism of action was investigated through pretreatments with prazosin 1 mg/kg intraperitoneal (α1 receptor antagonist), yohimbine 5 mg/kg intraperitoneal (α2 receptor antagonist), pCPA 300 mg/kg intraperitoneal (serotonin synthesis inhibitor) and MK-801 0.25 mg/kg intraperitoneal (N-methyl-D-aspartic acid receptor antagonist).. The antinociceptive effect of uliginosin B (15 and 90 mg/kg, i.p.) was reduced significantly by pCPA and MK-801. Prazosin and yohimbine improved the antinociceptive effect of the highest dose (90 mg/kg, i.p.) of uliginosin B only. The ataxic effect of uliginosin B (90 mg/kg, i.p.) was completely prevented by pretreatment with pCPA or MK-801, but it was unaffected by pretreatment with prazosin or yohimbine.. These data confirm the contribution of monoaminergic neurotransmission as well as provide the first evidence of glutamatergic neurotransmission contribution to the uliginosin B effects.

Topics: Analgesics; Animals; Behavior, Animal; Biogenic Monoamines; Glutamic Acid; Hypericum; Male; Mice, Inbred Strains; Pain; Pain Measurement; Pain Threshold; Phloroglucinol; Plant Components, Aerial; Plant Extracts; Synaptic Transmission

Uliginosin B is a natural phloroglucinol derivative, obtained from Hypericum species native to South America. Previous studies have shown that uliginosin B presents antidepressant-like and antinociceptive effects. Although its mechanism of action is still not completely elucidated, it is known that it involves the activation of monoaminergic neurotransmission. The aim of the current study was to further investigate the antinociceptive mechanism of action of uliginosin B by combining it with different drugs used for treating pain in clinical practice. The intraperitoneal administration of uliginosin B, morphine, amitriptyline and clonidine, alone or in mixture, produced a dose-dependent antinociceptive effect in the hot-plate assay in mice. The effect of the mixtures of drugs was studied using an adapted isobologram analysis at the effect level of 50% of the maximal effect observed. The analysis showed that the interactions between uliginosin B and morphine was synergistic, while the interactions between uliginosin B and amitriptyline or clonidine were additive. These findings point to uliginosin B as a potential adjuvant for pain pharmacotherapy, especially for opioid analgesia.

Topics: Amitriptyline; Analgesics; Animals; Clonidine; Dose-Response Relationship, Drug; Drug Synergism; Hypericum; Male; Mice; Morphine; Pain; Phloroglucinol; Plant Components, Aerial

To observe the efficacy of a plant-derived wound dressing (1 Primary Wound Dressing®), a mixture of hypericum and neem oil, in different types of paediatric burns.. A retrospective review was conducted over the complete healing course of 9 paediatric patients with a mean age of 8.17±3.35 (1-11 years), presenting mixed, partial or full-thickness burns. The treatment applied by the wound care specialist consisted of daily cleansing of the wound with a saline solution and application of 1 Primary Wound Dressing on the whole wound surface. There was no application of a secondary dressing. The time to heal, wound size, ease of handling, pain and complications were recorded. Procedural and background pain were observed in six of the patients older than 5 years (mean age 9.6±2.39, range 8-11 years). Due to the small number of patients examined during the period studied, it was not possible to perform statistical analyses.. The mean wound size was 50.76±48.32cm2 (4.63-132.0cm2). A rapid induction of granulation tissue and re-epithelialisation was observed. Time to complete healing was 16.6±4.69 days (10-22 days). No complications related to wound infection was observed. The 6 patients older than five years reported a strong relief of pain, from an initial value of 7-8 out of 10 to 0 out of 10 within the first week of treatment. This remained at the 0 out of 10 level during the second and third weeks of treatment.. This retrospective, non-controlled examination suggests that 1 Primary Wound Dressing could be an effective therapy for the treatment of burn wounds, with benefits including pain reduction and simplicity of use. Further evaluations with a larger population are required to document the effectiveness of this plant-derived wound dressing in a controlled fashion.. There were no external sources of funding for this study. F. Carnevali is a researcher and co-inventor of 1 Primary Wound Dressing®.

Topics: Azadirachta; Bolivia; Burns; Child; Child, Preschool; Female; Glycerides; Humans; Hypericum; Infant; Male; Occlusive Dressings; Pain; Phytotherapy; Plant Extracts; Retrospective Studies; Terpenes; Wound Healing; Wound Infection

Despite the substantial improvement that antimigraine drugs brought to migraineurs, there is the need for a long-acting and better tolerated migraine treatment than actual pharmacotherapy. St. John's wort (SJW), a medicinal plant endowed with a favourable tolerability profile, showed numerous bioactivities. We here investigated the pain-relieving property of SJW and its main components, hypericin and flavonoids, in a mouse model induced by nitric oxide (NO) donors administration.. The NO donors nitroglycerin and sodium nitroprusside (SNP) induced allodynia (cold plate test) and hyperalgesia (hot plate test). Western blotting experiments were performed to detect c-Fos and protein kinase C (PKC) expression within periaqueductal grey matter (PAG).. A single oral administration of an SJW dried extract (5 mg/kg p.o.) produced a prolonged relief from pain hypersensitivity. Similarly, preventive SJW administration increased the latency to the induction of hyperalgesia and reduced the duration of the painful symptomatology. Among SJW main components, hypericin showed a similar profile of activity, whereas flavonoids were devoid of any antihyperalgesic effect. To clarify the cellular pathways involved in the SJW mechanism of action, we examined the effects induced by the herbal drug on PKC. NO donors' administration upregulated and increased phosphorylation of PKCγ and PKCε isoforms within PAG that was prevented by SJW treatment. The absence of behavioural side effects or altered animals' locomotor activity by SJW was demonstrated.. These results suggest SJW as a safe therapeutic perspective for migraine pain, and indicate PKC as an innovative target for antimigraine therapy.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Blotting, Western; Cold Temperature; Ergotamine; Hot Temperature; Hyperalgesia; Hypericum; Indomethacin; Injections, Intraventricular; Male; Mice; Migraine Disorders; Motor Activity; Nitric Oxide Donors; Nitroglycerin; Nitroprusside; Pain; Periaqueductal Gray; Plant Extracts; Postural Balance; Protein Kinase C; Vasoconstrictor Agents; Vasodilator Agents

The present study investigated the antinociceptive activity of different extracts prepared from the aerial parts of blossom of Hypericum grandifolium Choisy-a species native to the Macaronesian Region-using the acetic acid-induced writhing, formalin and tail flick test in mice. Oral administration of methanol extract (500 and 1,000 mg/kg p.o.), the aqueous, butanol and chloroform fractions (500 mg/kg p.o.) as well as subfractions F2 and F3 (45 mg/kg p.o.) from the chloroform fraction significantly inhibited acetic acid-induced writhing, with values ranging from 28 to 50% of inhibition. The methanol extract (1,000 mg/kg p.o.) and chloroform fraction (500 mg/kg p.o.) significantly reduced both phases of formalin-induced pain (with inhibition values ranging from 18 to 53%), whereas subfraction F2 (45 mg/kg p.o.) significantly inhibited the late phase (30%). In the tail flick assay, only the chloroform fraction (500 mg/kg p.o.) significantly prolonged the tail flick response. Different constituents, such as flavonoids and benzophenone derivatives, could account for the effects observed. Taking together, the results indicate that Hypericum grandifolium Choisy possesses both peripheral and central antinociceptive activities in mice, suggesting an interesting therapeutic potential for this species in pain diseases.

Topics: Acetic Acid; Analgesics; Animals; Benzophenones; Chromatography, High Pressure Liquid; Female; Flavonoids; Formaldehyde; Hypericum; Male; Mass Spectrometry; Mice; Pain; Plant Extracts

The main purpose of the present study was to develop a novel formulation of St. John's Wort (SJW) extract with the aim of improving its pharmacokinetics and anti-nociceptive effect. Several formulations of SJW were prepared, including cyclodextrin inclusion (SJW-CD), solid dispersion (SJW-SD), dry-emulsion (SJW-DE), and nano-emulsion (SJW-NE). Physicochemical properties of SJW formulations were characterized with a focus on the morphology, dissolution behavior, colloidal properties, and dispersion stability in water. Although all the SJW formulations and SJW extract itself exhibited fine dissolution behavior in water, SJW extract and most formulations tended to cream, aggregate, or flocculate after dispersion in distilled water. In contrast, there were no significant changes in appearance and particle size of the SJW-NE for at least a few weeks, suggesting that SJW-NE was the most stable form as a carrier of SJW in the present study. After oral administration of the SJW-NE formulation (5.2 mg hyperforin/kg) in mice, higher hyperforin exposure in plasma (1188 ± 41 nM·h) and the brain (52.9 ± 1.6 pmol/g tissue·h) was observed with 2.8- and 1.3-fold increases of the area under the concentration curve from 0 to 6 hours (AUC(0-6)) compared to those of the SJW extract (417 ± 41 nM·h in plasma and 41.6 ± 1.5 pmol/g tissue·h in the brain). In the formalin test for scoring properties of the first and second phases of the pain response in mice, single oral administration of SJW-NE significantly reduced the nociceptive response compared with SJW extract. From these findings, the NE approach might be efficacious in improving the oral bioavailability and anti-nociceptive effect of SJW extract.

Topics: Administration, Oral; Analgesics; Animals; Biological Availability; Chemistry, Pharmaceutical; Drug Carriers; Drug Stability; Hypericum; Male; Mice; Mice, Inbred ICR; Pain; Particle Size; Plant Extracts; Solubility

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

Current pharmacological treatments for neuropathic pain have limited efficacy and severe side-effect limitations. St. John's Wort (SJW) is a medicinal plant, mainly used as antidepressant, with a favourable side-effect profile. We here demonstrate the ability of SJW to relieve neuropathic pain in rat models. The antihyperalgesic profile and mechanism of action of SJW and its main components were studied in two rat models of neuropathic pain: the chronic constriction injury and the repeated administration of oxaliplatin. SJW, acutely administered at low doses (30-60 mg kg(-1) p.o.), reversed mechanical hyperalgesia with a prolonged effect, being effective up to 180 min after injection. Further examinations of the SJW main components revealed that hyperforin and hypericin were responsible for the antihyperalgesic properties whereas flavonoids were ineffective. The effect of SJW on the PKC expression and activation was investigated in the periaqueductal grey (PAG) area by immunoblotting experiments. Mechanistic studies showed a robust over-expression and hyperphosphorylation of the PKCgamma (227.0+/-15.0% of control) and PKCepsilon (213.9+/-17.0) isoforms in the rat PAG area. A single oral administration of SJW produced a significant decrease of the PKCgamma (131.8+/-10.0) and PKCepsilon (105.2+/-12.0) phosphorylation in the PAG area due to the presence of hypericin. Furthermore, SJW showed a dual mechanism of action since hyperforin antinociception involves an opioid-dependent pathway. Rats undergoing treatment with SJW and purified components did not show any behavioural side effects or signs of altered locomotor activity. Our results indicate SJW as a prolonged antihyperalgesic treatment through inhibition of PKC isoforms and their phosphorylation.

Topics: Analgesics; Animals; Anthracenes; Hypericum; Male; Pain; Perylene; Phytotherapy; Plant Extracts; Protein Kinase C; Protein Kinase C-epsilon; Rats; Rats, Sprague-Dawley

Several species of the genus Hypericum (Guttiferae) have been used for analgesic purposes all over the world and some of them have demonstrated to possess this effect in rodents. This study describes the antinociceptive effect of the cyclohexane extract from aerial parts of H. polyanthemum (POL) as well as of benzopyrans, 6-isobutyryl-5,7-dimethoxy-2,2-dimethyl-benzopyran (HP1), 7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethyl-benzopyran (HP2), and 5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethyl-benzopyran (HP3), which are the main components of POL. The antinociceptive effect was evaluated through hot-plate and writhing tests in mice, and the opioid system involvement was assessed by using naloxone (2.5 mg/kg, s.c.) antagonism. In the hot-plate test, POL (45, 90, 180 mg/kg, p.o) showed a dose-dependent effect, and out of the benzopyrans only HP1 (30, 60, 90 mg/kg, i.p.) was active. Its effect was also dose-dependent, with the maximum reached at 60 mg/kg. HP1 60 mg/kg (p.o.) also inhibited acetic acid-induced writhing in 58%. The pretreatment with naloxone abolished the antinociceptive effect of HP1 60 mg/kg (i.p) in the hot plate. Furthermore, the H. polyanthemum cyclohexane extract and HP1 did not affect the mice performance in the rota-rod apparatus suggesting that at antinociceptive doses they do not present gross neurotoxicity nor induce motor impairment. From these data it is reasonable to assume that the benzopyran HP1 accounts for the H. polyanthemum cyclohexane extract antinociceptive effect, and this effect is, at least in part, mediated by an opioid-like mechanism.

Topics: Acetic Acid; Analgesics, Opioid; Animals; Behavior, Animal; Benzopyrans; Dose-Response Relationship, Drug; Hot Temperature; Hypericum; Male; Mice; Mice, Inbred Strains; Naloxone; Narcotic Antagonists; Pain; Phytotherapy; Plant Components, Aerial; Plant Extracts

The present study investigates the analgesic and topical anti-inflammatory activities of the infusion, methanol extract and fractions of the aerial part in blossom of Hypericum canariense L. and Hypericum glandulosum Ait. in mice. The acetic acid-induced writhing test, tail flick test and the tetradecanoylphorbol acetate (TPA)-induced ear inflammation model in mice were used to determine these effects. Our findings show that oral administration of methanol extracts, and the aqueous, butanol and chloroform fractions of both species and the infusions of Hypericum glandulosum significantly inhibit acetic acid-induced writhing in mice. Only the infusion, methanol extract and butanol and chloroform fractions of Hypericum glandulosum were significantly active in the tail flick assay, suggesting that they may have central analgesic properties. On the other hand, the topical treatment of all extracts tested from both species, with the exception of the infusions and the Hypericum canariense aqueous fraction, significantly reduced the TPA-induced ear oedema. In conclusion, the results indicate analgesic and topical anti-inflammatory activities in mice for the Hypericum species studied.

Topics: Acetic Acid; Administration, Oral; Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ear; Female; Flowers; Hypericum; Inflammation; Male; Mice; Pain; Phytotherapy; Plant Extracts; Tail; Tetradecanoylphorbol Acetate

The pharmacological activity of Hypericum perforatum was assessed using models of inflammation, nociception, and gastric mucosal injury in rats. H. perforatum was given systemically as well as orally. When administered systemically, H. perforatum (50-300 mg/kg, s.c.) produced a dose-related and significant inhibition of the edematogenic response to s.p. injection of carrageenan. The percentages of maximal inhibition by the above doses were 53.7, 61.3, and 75.3%, respectively (compared to 90% after 50 mg/kg fluoxetine and 60.7% after 72 mg/kg etodolac). In tests of nociception, H. perforatum, administered orally, displayed antinociceptive activity in the tail electric stimulation and hot plate tests. The antinociceptive activity was observed with 25 mg/kg and a maximal increase in hot plate latency by 50% (compared to 73.2 and 77.8% increases by 5 or 10 mg/kg fluoxetine, respectively). In contrast, the acetic acid-induced (0.6%, i.p.) writhing was significantly reduced by fluoxetine or etodolac, but not H. perforatum. Also, the nociceptive response caused by i.p. injection of capsaicin (1.6 microg/paw) was unaffected by H. perforatum, but reduced by fluoxetine. Injection of H. perforatum (50, 125, or 250 mg/kg, s.c.) to pylorus-ligated rats, decreased gastric acid secretion, but increased indomethacin-induced gastric mucosal lesions dose dependently. These results demonstrate that H. perforatum exhibits antiedematogenic and antinociceptive properties, which may be of value for the management of inflammatory painful conditions. The agent, however, causes gastric irritation and may aggravate that of NSAIDs.

Topics: Acetic Acid; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Capsaicin; Carrageenan; Drug Evaluation, Preclinical; Edema; Electroshock; Etodolac; Fluoxetine; Gastric Acid; Gastric Mucosa; Hot Temperature; Hypericum; Indomethacin; Pain; Peritonitis; Plant Extracts; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Stomach Ulcer

Hydroalcoholic extracts from species Hypericum brasiliense Choisy (HB) and Hypericum cordatum (Vell. Conc.) N. Robson (HC), were evaluated on the central nervous system (CNS) in some pharmacological tests. Signs of toxicity were observed for both species during the initial screening when high doses of up to 100 mg/kg (i.p.) and 1000 mg/kg (oral) were utilized. HC presented greater toxicity, with LD(50) of 269 mg/kg, as compared to HB (537 mg/kg). Alterations in sleeping time and in motor coordination were not observed both for HB and for HC. On the other hand, both species showed signs of general depressant action on the CNS, verified by decreased motor activity. Furthermore, animals treated with HB presented an increase in response time to thermal stimulus with doses of 50 mg/kg (i.p.) and 500 mg/kg (oral) suggesting possible analgesic action. Both HB and HC were tested in animal models to verify antidepressant action (forced swimming and hypothermy induced by apomorphine). In these tests, neither of the plants inhibited hypothermy, nor did they reduce immobility time in forced swimming.

Topics: Administration, Oral; Analgesics; Animals; Antidepressive Agents; Apomorphine; Central Nervous System; Dose-Response Relationship, Drug; Hypericum; Hypothermia; Injections, Intraperitoneal; Lethal Dose 50; Mice; Motor Activity; Pain; Pain Measurement; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Sleep