%0 Journal Article
%T Polysaccharide-rich extract of Genipa americana leaves exerts anti-inflammatory effects modulated by platelet mediators.
%A Araujo DF
%A Holanda BF
%A Nascimento FLFD
%A Martins AB
%A Silva ALM
%A Pereira MG
%A Freitas Pires A
%A Assreuy AMS
%J J Ethnopharmacol
%V 319
%N 0
%D 2024 Jan 30
%M 37793578
%F 5.195
%R 10.1016/j.jep.2023.117234
%X <B>BACKGROUND: </B>Genipa americana L. (Rubiaceae) leaves are traditionally used to treat fever, pharyngitis, healing, luxation and bruises.<BR><B>OBJECTIVE: </B>This study aimed to investigate the anti-inflammatory effect of the polysaccharide-rich extract of G. americana leaves (PE-Ga) in acute inflammation models and underlying mechanisms associated with platelet activity.<BR><B>METHODS: </B>Rats received PE-Ga (0.3-3.0 mg/kg; IV) 30 min before injection (IP or SC) of zymosan, serotonin, PGE2, PLA2, PAF or L-arginine, and evaluated in the models of paw edema and acute peritonits. The blockage of plasma serotonin reuptake into platelets was performed with fluoxetine (40 mg/kg; IP).<BR><B>RESULTS: </B>In vitro, PE-Ga inhibited ADP-induced platelet aggregation up to 49%. In the edema model, PE-Ga reduced (41%) the time-course of the edema induced by zymosan, mainly the last phase (62%), as well as that induced by PLA2 (32%), PAF (35%), L-arginine (36%), PGE2 (49%) or serotonin (54% AUC); and reversed paw hypernociception induced by PGE2 or serotonin. In the peritonitis model, PE-Ga reversed abdominal hypernociception and reduced leukocyte migration induced by zymosan to blood (38%) and peritoneal cavity (55%), mainly neutrophils (70%). PE-GA also decreased leukocyte rolling (32%) and adhesion (47%), and increased the rolling velocity 2.2-fold. In the peritoneal fluid, PE-Ga reversed P-selectin and reduced total proteins (17%), MDA (40%), NO2-/NO3- (27%), and MPO activity (43%) but increased catalase activity 3.3-fold compared to zymosan. In addition, fluoxetine reversed PE-Ga anti-inflammatory effect on leukocyte migration and adhesion.<BR><B>CONCLUSIONS: </B>PE-Ga exerts antiplatelet and anti-inflammatory effects in acute inflammation induced by zymosan, being modulated by P-selectin and platelet serotonin, among other inflammatory mediators.