Polysaccharide-rich extract of Genipa americana leaves exerts anti-inflammatory effects modulated by platelet mediators

J Ethnopharmacol. 2024 Jan 30;319(Pt 2):117234. doi: 10.1016/j.jep.2023.117234. Epub 2023 Oct 2.

Abstract

Ethnopharmacological relevance: Genipa americana L. (Rubiaceae) leaves are traditionally used to treat fever, pharyngitis, healing, luxation and bruises.

Aim of the study: 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.

Materials and 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.

Keywords: Inflammation; Jenipapeiro; Oxidative stress.; Plant polysaccharides; Platelet.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Arginine
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / metabolism
  • Fluoxetine
  • Inflammation / drug therapy
  • P-Selectin
  • Phospholipases A2
  • Plant Extracts* / adverse effects
  • Polysaccharides / pharmacology
  • Polysaccharides / therapeutic use
  • Rats
  • Rubiaceae*
  • Serotonin
  • Zymosan

Substances

  • Plant Extracts
  • P-Selectin
  • Fluoxetine
  • Serotonin
  • Zymosan
  • Polysaccharides
  • Anti-Inflammatory Agents
  • Arginine
  • Phospholipases A2