Suppression of COX-2, IL-1& and TNF-&, expression and leukocyte infiltration in inflamed skin by bioactive compounds from Rosmarinus officinalis L.

ELEONORA S. MENGONI ; GABRIEL VICHERA; LUCIANO A. RIGANO,; MARCELO L. RODRIGUEZ- PUEBLA; SILVIA R. GALLIANO; EDUARDO E. CAFFERATA,; OMAR H. PIVETTA; SIVIA MORENO ; ADRIáN A.VOJNOV

FITOTERAPIA

ELSEVIER SCIENCE BV

Lugar: Milton Road, Cambridge, United Kingdom; Año: 2011 vol. 82 p. 414 - 421

0367-326X

In the present study, we evaluated the effects of extracts and purified compounds from 37 fresh leaves of Rosmarinus officinalis L. Pretreatment with the major anti-inflammatory 38 compounds, carnosic acid (CA) and carnosol (CS), inhibited phorbol 12-myristate 13- acetate (PMA)-induced ear inflammation in mice with an EC50 of 10.20 �gg/cm2 39 and 10.70 �gg/cm240 , respectively. To further understand the anti-inflammatory mechanism of 41 these compounds, we analyzed the in vivo expression of several inflammation42 associated genes in mouse skin by reverse transcriptase�Vpolymerase chain reaction (RT43 PCR). Our data showed that CA and CS reduced the expression of IL-1�҃n�nand TNF- 44 �ónbut had less effect on fibronectin and ICAM-1 expression. Interestingly, both 45 compounds selectively inhibited COX-2 but not COX-1. Histopathological analysis of 46 hematoxylin and eosin (H&E)-stained tissue revealed a marked reduction in leukocyte 47 infiltration and epidermal ulceration of PMA-treated ears when ears were pretreated 48 with ethanolic extracts or pure CA. In vitro, we showed that ethanolic extract, carnosic 49 acid and carnosol significantly inhibited the overproduction of nitric oxide (NO) in a 50 dose-dependent manner in the RAW 264.7 murine macrophage cell line. For the first 51 time in vivo, we showed that CA and CS differentially regulate the expression of 52 inflammation-associated genes, thus demonstrating the pharmacological basis for the 53 anti-inflammatory properties reported for CA and CS.