Pentacyclic triterpenoids, alpha,beta-amyrins, suppress the scratching behavior in a mouse model of pruritus.
In the search for natural compounds useful against pruritus, alpha,beta-amyrins, the pentacyclic triterpenes isolated from the resin of popular medicinal plant Protium heptaphyllum were examined on scratching behavior induced by dextran T40 and compound 48/80 in mice. The animals were pretreated orally with alpha,beta-amyrins (50, 100 and 200 mg/kg) or cyproheptadine (10 mg/kg), an antagonist of histamine and serotonin receptors and 2 h later, they were given subcutaneous injections of dextran T40 (75 mg/kg) or compound 48/80 (3 mg/kg) into the rostral back, and scratching was quantified for 20 min. The scratching behavior induced by dextran T40 and compound 48/80 was significantly inhibited in mice pretreated with alpha,beta-amyrins (100 and 200 mg/kg) or cyproheptadine (10 mg/kg), In addition, the compound 48/80-elicited degranulation of rat peritoneal mast cells (ex vivo) was also markedly reduced in animals pretreated with alpha,beta-amyrins (100 mg/kg) or ketotifen (1 mg/kg), a known mast cell stabilizer. In the open-field test, alpha,beta-amyrins (100 and 200 mg/kg)-pretreated mice showed no impairment of spontaneous locomotion, suggesting that these triterpenoids possess no sedative activity that could account for suppression of scratching behavior. These results clearly indicate the antipruritic effect of alpha,beta-amyrins and suggest that this effect may be related to a stabilizing action on mast cell membrane.
Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceara, Rua Cel Nunes de Melo-1127, Caixa Postal-3157, 60430-270 Fortaleza, CE, Brazil.
Francisco A
FA
Oliveira
Roberto C P
RC
Lima-Junior
Wilcare M
WM
Cordeiro
Gerardo M
GM
Vieira-Júnior
Mariana H
MH
Chaves
Fernanda R C
FR
Almeida
Regilane M
RM
Silva
Flavia A
FA
Santos
Vietla S N
VS
Rao
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015550:Cell Degranulation / Q000187:drug effects; D003533:Cyproheptadine / Q000494:pharmacology; D003911:Dextrans; D004723:Endorphins / Q000502:physiology; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007665:Ketotifen / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000648:ultrastructure; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010529:Peritoneal Cavity / Q000166:cytology; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology*; D017450:Receptors, Opioid, mu / Q000187:drug effects; D003189:p-Methoxy-N-methylphenethylamine
D000701:Analgesics, Opioid; D003911:Dextrans; D004723:Endorphins; D006634:Histamine H1 Antagonists; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D003533:Cyproheptadine; D009270:Naloxone; D003189:p-Methoxy-N-methylphenethylamine; D009828:Oleanolic Acid; D009020:Morphine; C036380:beta-amyrin; D007665:Ketotifen