Inhibition of neutrophil migration and reduction of oxidative stress by ethyl p-coumarate in acute and chronic inflammatory models.

BACKGROUND: It is well known that medicinal plants and their products are relevant candidates for the treatment of inflammatory conditions. Ethyl p-coumarate is a phenylpropanoid that has similar structure to others anti-inflammatory and antioxidant substances. However, these activities have never been tested. PURPOSE: The aim of this study was to investigate the effect of ethyl p-coumarate on inflammatory and oxidative stress parameters. STUDY DESIGN: This is an experimental study to evaluate the anti-inflammatory and antioxidant activities of ethyl p-coumarate in acute and chronic models of inflammation. METHODS: The anti-inflammatory effect of ethyl p-coumarate was evaluated in Swiss mice by carrageenan-induced paw edema model (1%, 50 µl), followed by histological analysis, and edema induced by compound 48/80 (12 µg/paw), histamine (100  µg/paw), serotonin (100 µg/paw) and prostaglandin E2 (3 nmol/paw) in comparison to indomethacin treatment (10 mg/kg, p.o.). In addition, peritonitis was induced by carrageenan (500 µg/cavity) to neutrophil and total leukocytes counting, myeloperoxidase (MPO), interleukin 6 (IL-6) and 8 (IL-8), nitrite (NO2-), glutathione (GSH) and malondialdehyde (MDA) measurements. The arthritis model was induced with Freund's complete adjuvant (id. 0.1 ml) in female Wistar rats, with measurement of joint diameter and X-ray. Changes in gastric tissue of Swiss mice were analyzed in comparison to indomethacin (20  mg/kg, p.o.). RESULTS: After treatment with ethyl p-coumarate, the animals had no apparent toxic effects, and significantly inhibited paw edema induced by edematogenic agents, neutrophil (p < 0.001) and total leukocyte (p < 0.001) migration, MPO (p < 0.01), IL-6 (p < 0.05) and IL-8 (p < 0.5), MDA (p < 0.5), GSH (p < 0.5), NO2- (p < 0.001), joint thickness and bones changes. Furthermore, were not observed significant formation of gastric lesions. CONCLUSION: Taken together, these results suggest that ethyl p-coumarate exhibits anti-inflammatory activity through the inhibition of inflammatory mediators and leukocyte migration without causing gastric lesions.

Antidiarrheal effects of water-soluble proteins from Plumeria pudica latex in mice.

The water-soluble protein fraction obtained from Plumeria pudica (LPPp) latex has previously been demonstrated to have anti-inflammatory and antinociceptive effects. In the present study, LPPp was tested for activity against diarrhea induced by castor oil, prostaglandin E2 (PGE2) or cholera toxin. Different doses of LPPp (10, 20 or 40mg/kg) significantly inhibited the percentage of diarrheal stools (31.18%, 42.97% and 59.70%, respectively) induced by castor oil. This event was followed by significant reduction of both intestinal fluid accumulation (31.42%; LPPp 40mg/kg) and intestinal transit (68.4%; LPPp 40mg/kg). The pretreatment of animals with LPPp (40mg/kg) prevented glutathione and malondialdehyde alterations induced by castor oil. The effects of LPPp against diarrhea induced by castor oil were lost when the fraction was submitted to protein denaturing treatment with heat. LPPp (40mg/kg) also inhibited the average volume of intestinal fluid induced by PGE2 (inhibition of 46.0%). Furthermore, LPPp (40mg/kg) prevented intestinal fluid secretion accumulation (37.7%) and chloride ion concentration (50.2%) induced by cholera toxin. In parallel, colorimetric assays demonstrated that proteinases, chitinases and proteinase inhibitors were found in LPPp. Our data suggest that the antidiarrheal effect of LPPp is due to its protein content and is probably associated with its anti-inflammatory properties.