OBJECTIVE: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.
目的:本研究旨在研究富含多糖的美洲甘草叶提取物(PE-Ga)在急性炎症模型中的抗炎作用及其与血小板活性相关的潜在机制。
方法:大鼠在注射(IP或SC)酵母聚糖前30分钟接受PE-Ga(0.3-3.0mg/kg;IV),血清素,PGE2,PLA2,PAF或L-精氨酸,并在爪子水肿和急性腹膜炎模型中进行评估。用氟西汀(40mg/kg;IP)阻断血浆5-羟色胺再摄取进入血小板。
结果:体外,PE-Ga抑制ADP诱导的血小板聚集达49%。在水肿模型中,PE-Ga减少了(41%)酵母聚糖诱导的水肿的时间进程,主要是最后阶段(62%),以及由PLA2诱导的(32%),PAF(35%),L-精氨酸(36%),PGE2(49%)或5-羟色胺(54%AUC);并逆转了PGE2或5-羟色胺诱导的爪痛觉过敏。在腹膜炎模型中,PE-Ga逆转了酵母聚糖诱导的腹部高伤害性感受,并减少了白细胞向血液(38%)和腹膜腔(55%)的迁移,主要是中性粒细胞(70%)。PE-GA还降低了白细胞滚动(32%)和粘附(47%),并将滚动速度提高了2.2倍。在腹膜液中,PE-Ga逆转P-选择素并降低总蛋白(17%),MDA(40%),NO2-/NO3-(27%),和MPO活性(43%),但与酵母聚糖相比,过氧化氢酶活性增加了3.3倍。此外,氟西汀逆转PE-Ga对白细胞迁移和粘附的抗炎作用。
结论:PE-Ga在酵母聚糖诱导的急性炎症中发挥抗血小板和抗炎作用,由P-选择素和血小板5-羟色胺调节,在其他炎症介质中。