ABSTRACT
This study investigated the possible antinociceptive effect of the crude extract, fractions and pure compounds (three alkaloids) obtained from fruits of Piper tuberculatum JACQ. (Piperaceae) in acetic acid-induced visceral pain in mice. Oral administration of crude extract and fractions (CH(2)Cl(2), EtOAc, methanol and hexane) (3-300 mg kg(-1)) caused a dose-related and significant inhibition of the acetic acid-induced visceral nociceptive response. The crude extract, dichloromethane (CH(2)Cl(2)) and ethyl acetate (EtOAc) fractions were more potent than methanol and hexane fractions. The isolated alkaloids dihydro-piplartine, piplartine and 3,4,5-trimethoxydihydrocinnamic acid (0.0001-30 mg kg(-1)) exhibited significant and dose-related antinociceptive effects against acetic acid-induced visceral pain. The results show, for the first time, that crude extract, fractions and pure compounds obtained from P. tuberculatum produce marked antinociception against the acetic acid-induced visceral nociceptive response, supporting the ethnomedical use of P. tuberculatum.
Subject(s)
Abdominal Pain/drug therapy , Alkaloids/therapeutic use , Analgesics/therapeutic use , Phytotherapy , Piper/chemistry , Plant Extracts/therapeutic use , Abdominal Pain/chemically induced , Acetic Acid , Alkaloids/isolation & purification , Alkaloids/pharmacology , Analgesics/isolation & purification , Analgesics/pharmacology , Animals , Dose-Response Relationship, Drug , Female , Fruit , Male , Mice , Plant Extracts/chemistry , Plant Extracts/pharmacologyABSTRACT
The present study investigated the possible involvement of the glutamatergic and neurokinin systems in the antinociception caused by triterpene 3beta, 6beta, 16beta-trihydroxylup-20(29)-ene (TTHL) in mice. TTHL given by intraperitoneal (i.p., 2.1-65.5micromol/kg), intraplantar (i.pl., 6.5-65.5nmol/paw) or intrathecal (i.t., 21.8-655nmol/site) routes, produced dose-dependent inhibition of glutamate-induced nociception with ID(50) values of 12micromol/kg; 34.2nmol/paw; 233.8nmol/site and inhibitions of 78+/-6; 82+/-4 and 77+/-8%, respectively. I.t. injection of TTHL (6.5-218nmol/site, co-administered) also caused significant and dose-dependent reduction of nociceptive response induced by i.t. injection of glutamate (175nmol/site), with ID(50) value of 54.5nmol/site and inhibition of 51+/-6%. Moreover, TTHL (65.5nmol/site) co-injected by i.t. route with agonist caused marked reduction of nociceptive responses induced by N-methyl-d-aspartate (NMDA, 450pmol/site), (+/-)-1-aminocyclopentane-trans-1,3 dicarboxylic acid (trans-ACPD, 10nmol/site) and substance P (100pmol/site), with inhibitions of 81+/-7; 79+/-7; 81+/-11%, respectively. Conversely, TTHL had no effect on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 135pmol/site) and kainic acid (kainate, 110pmol/site)-induced nociception. Moreover, the association of sub-effective doses of TTHL (6.5nmol/site, i.t.) and MK-801(1nmol/site, i.t.; non-competitive NMDA antagonist) or (RS)-MCPG (30nmol/site, i.t.; non-selective group I/group II metabotropic glutamate receptor antagonist) produced a synergic antinociceptive effect in the nociception induced by NMDA or trans-ACPD, respectively. Together, these results provide experimental evidence for the involvement of the glutamatergic system (NMDA and metabotropic glutamate receptors) in the antinociceptive action caused by TTHL in mice.
