Involvement of the L-arginine-nitric oxide pathway in the antinociception caused by fruits of Prosopis strombulifera (Lam.) Benth.
BACKGROUND
Prosopis strombulifera (Lam.) Benth. is a rhizomatous shrub that grows in the north and central zone of Argentina. In folk medicine, the fruits of this plant have been used as an astringent, anti-inflammatory and odontalgic agent and anti-diarrheic.


OBJECTIVE
To investigate the antinociceptive effect of ethanol (EE), chloroform (CE) and ethyl acetate (EtOAcE) extracts of Prosopis strombulifera fruits and the involvement of the l-arginine-nitric oxide pathway in this effect.


METHODS
The antinociceptive effects of the EE, CE and EtOAcE of Prosopis strombulifera fruits were evaluated in vivo using the formalin-induced pain test in mice with aspirin and morphine as reference antinociceptive compounds. The participation of the l-arginine-nitric oxide pathway in the antinociceptive effect was investigated in the same animal model using l-arginine as a nitric oxide (NO) precursor. The in vitro inhibitory effect of the extracts on LPS-induced nitric oxide production and iNOS expression was investigated in a J774A.1 macrophage-derived cell line.


RESULTS
CE (300mg/kg), in contrast to EE and EtOAcE, caused significant inhibition (p<0.05) of the in vivo nociceptive response. Moreover, CE (100-1000mg/kg, p.o.) produced a dose-dependent inhibition of the neurogenic and the inflammatory phases of the formalin test with inhibition values (at 600mg/kg) of 42±7% and 62±7%, respectively. CE inhibition was more potent in the inflammatory phase, with an ID(50) of 400.1 (252.2-634.8)mg/kg. The antinociception caused by CE (600mg/kg, p.o.) was significantly attenuated (p<0.05) by i.p. treatment of mice with l-arginine (600mg/kg). In addition, CE (100μg/mL) produced significant in vitro inhibition (p<0.001) of LPS-induced NO production, which was not observed with EE and EtOAcE at the same concentration. The inhibition of NO production by CE (10-100μg/mL) was dose-dependent, with an IC(50) of 39.8 (34.4-46.1)μg/mL, and CE significantly inhibited LPS-induced iNOS expression in J774A.1 cells.


CONCLUSIONS
This study supports, in part, the ethnomedical use of Prosopis strombulifera fruits by showing that its CE produces moderate antinociception in vivo. The findings also provide scientific information for understanding the molecular mechanism involved in the analgesic effect of this plant.
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina.
Alejandra Cristina
AC
Saragusti
Pamela Soledad
PS
Bustos
Luana
L
Pierosan
José Luis
JL
Cabrera
Gustavo Alberto
GA
Chiabrando
Adair Roberto Soares
AR
Santos
María Gabriela
MG
Ortega
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001118:Argentina; D001120:Arginine / Q000378:metabolism* / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005638:Fruit; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D029862:Prosopis
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D009569:Nitric Oxide; D009020:Morphine; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D001241:Aspirin