Effects of Myrcia pubipetala Miq (Myrtaceae) extract on innate inflammatory response.

Myrcia is a genus widespread in South America with many species presenting anti-inflammatory and biological properties. We investigated the anti-inflammatory activity of crude hydroalcoholic extract of Myrcia pubipetala leaves (CHE-MP) using macrophages (RAW 264.7), and the air pouch model in mice to evaluate leukocyte migration and mediator's release. Adhesion molecule expression, CD49 and CD18, was evaluated in neutrophils. In vitro, the CHE-MP significantly reduced nitric oxide (NO), interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF) levels in the exudate and the supernatant culture. CHE-MP did not present cytotoxicity and modulated the percentage of positive neutrophils for CD18 and its expression per cell, without modifying the expression of CD49, which corroborated with significantly reduced neutrophil migration to inflammatory exudate and subcutaneous tissue. Taken together, the data demonstrate that CHE-MP presents a potential activity on innate inflammatory.

Role of an indole-thiazolidine molecule PPAR pan-agonist and COX inhibitor on inflammation and microcirculatory damage in acute gastric lesions.

The present study aimed to show the in vivo mechanisms of action of an indole-thiazolidine molecule peroxisome-proliferator activated receptor pan-agonist (PPAR pan) and cyclooxygenase (COX) inhibitor, LYSO-7, in an ethanol/HCl-induced (Et/HCl) gastric lesion model. Swiss male mice were treated with vehicle, LYSO-7 or Bezafibrate (p.o.) 1 hour before oral administration of Et/HCl (60%/0.03M). In another set of assays, animals were injected i.p. with an anti-granulocyte antibody, GW9962 or L-NG-nitroarginine methyl ester (L-NAME) before treatment. One hour after Et/HCl administration, neutrophils were quantified in the blood and bone marrow and the gastric microcirculatory network was studied in situ. The gastric tissue was used to quantify the percentage of damaged area, as well as myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) protein and PPARγ protein and gene expression. Acid secretion was evaluated by the pylorus ligation model. LYSO-7 or Bezafibrate treatment reduced the necrotic area. LYSO-7 treatment enhanced PPARγ gene and protein expression in the stomach, and impaired local neutrophil influx and stasis of the microcirculatory network caused by Et/HCl administration. The effect seemed to be due to PPARγ agonist activity, as the LYSO-7 effect was abolished in GW9962 pre-treated mice. The reversal of microcirculatory stasis, but not neutrophil influx, was mediated by nitric oxide (NO), as L-NAME pre-treatment abolished the LYSO-7-mediated reestablishment of microcirculatory blood flow. This effect may depend on enhanced eNOS protein expression in injured gastric tissue. The pH and concentration of H(+) in the stomach were not modified by LYSO-7 treatment. In addition, LYSO-7 may induce less toxicity, as 28 days of oral treatment did not induce weight loss, as detected in pioglitazone treated mice. Thus, we show that LYSO-7 may be an effective treatment for gastric lesions by controlling neutrophil influx and microcirculatory blood flow mediated by NO.