title: St. John's wort relieves pain in an animal model of migraine.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These results suggest SJW as a safe therapeutic perspective for migraine pain, and indicate PKC as an innovative target for antimigraine therapy.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, Florence, Italy. nicoletta.galeotti@unifi.it
authors.forename: N
authors.initials: N
authors.lastname: Galeotti
authors.forename: C
authors.initials: C
authors.lastname: Ghelardini
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D003080:Cold Temperature; D004878:Ergotamine / Q000627:therapeutic use; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000523:psychology; D020902:Hypericum / Q000737:chemistry*; D007213:Indomethacin / Q000627:therapeutic use; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008881:Migraine Disorders / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D009043:Motor Activity / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin; D009599:Nitroprusside; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D010487:Periaqueductal Gray / Q000502:physiology; D010936:Plant Extracts / Q000627:therapeutic use; D004856:Postural Balance / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000627:therapeutic use; D014665:Vasodilator Agents
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020030:Nitric Oxide Donors; D010936:Plant Extracts; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D011493:Protein Kinase C; D005996:Nitroglycerin; D004878:Ergotamine; D007213:Indomethacin