In vitro modulation of inflammatory target gene expression by an association of Pterodon pubescens Benth. and Cordia verbenacea DC

Abstract

Inflammation is a complex immune response related to tissue and/or cellular damage caused by chemical, physical, immunological or microbial stimuli and is usually regulated by a cascade of many molecular interactions and biochemical reactions responsible for propagating and maturing the inflammatory response and involves the local vascular system, the immune system and various cell types. Leukocytes release algogenic substances, including acetylcholine, bradykinin, histamine, serotonin, substance P, PGE2, leukotrienes, TNF-±, IL-1², and cyclic adenosine monophosphate (cAMP). TNF-± can induce pain directly or via stimulation of the synthesis of IL-1², IL-6 and/or IL-8. IL-1² levels are usually elevated manifold during progression of auto-immune diseases in particular. IL-6 promotes inflammation by inducing neovascularization and hyperplasia, which is especially the case for chronic developments. IL-8 is a potent chemoattractant for T lymphocytes, neutrophils and eosinophils. As members of the c-c motif family, both RANTES (Regulated on Activation Normal T-Cell Expressed and Secreted) and MCP-1 (Monocyte Chemotactic Protein 1) depict mediators, potent chemo-attractants for macrophages and leukocyte activators. Pain appears due to direct effects of mediators resulting from both initial damage and inflammatory response. Non-steroidal anti-inflammatory drugs (NSAIDs) represent a group of more than 20 drugs that enjoy wide clinical application and present compounds with heterogeneous chemical structures that demonstrate efficacy for the treatment of pain and inflammation. Indiscriminate and continuous use of NSAIDs may lead to adverse effects including gastrointestinal disorders, gastric ulcers, renal toxicity, cardiovascular and central nervous system problems. Despite the major advances in understanding the molecular mechanisms involved in pain and inflammation, current therapies are usually insufficient because they have severe side effects or limited efficacy. The use of phytocomplexes may be an alternative for the treatment of inflammatory diseases. The species Cordia verbenacea DC and Pterodon pubescens Benth. are popularly used in the treatment of several inflammatory diseases and the association of these two plants presented a real synergistic effect, with an important antinociceptive and mainly anti-inflammatory response to experimental models in vivo, presenting better effects and prolongation of pharmacological activity, with lower effective doses of each extract when used in associations. Bearing in mind the promising anti-inflammatory activities of mixture of Pterodon pubescens Benth. and Cordia verbenacea DC and the lack of information concerning its pharmacological activity, the objective of this study is to investigate the effect of the association of both extracts on transcriptional activity of five different key targets in comparison to the separate extracts and their major isolated compounds, ±-humulene and compound m/z 404, to understand the synergism mechanism of action. (AU)