Clinical Pharmacology & Biopharmaceutics
Open Access

Abstract

Most anti-inflammatory and anticancer drugs produced are derived from naturally occurring compounds or their derivatives. There is a constant search for new metabolites from natural origin, particularly from plants, which have potential for efficacious drugs. Myrtaceae, a plant family present in tropical areas, is one of the most studied on biological activities. Myrciaria genus belongs to this family and comprises several species; however, few studies have shown their therapeutic potential. The present study aimed to investigate the anti- inflammatory potential and cytotoxicity of the ethanol extract of a species of the Myrciaria genus on RAW 267.4 macrophage cells, human peripheral blood mononuclear cells (PBMCs) and Jurkat acute T-lymphocytic leukemia cells. First, RAW 267.4 and PBMCs were treated with increasing concentrations of the extract to assess cytotoxicity for 48 h and 96 h using Alamar blue and Trypan blue exclusion, respectively. In addition, lymphoproliferation was assayed on phytohemagglutinin (PHA)stimulated PBMCs using MTT method. TNF-�± levels were determined by ELISA after RAW 267.4 and PBMCs were pre-incubated with the extract and then challenged with LPS. Protein expression of inflammation-associated markers (NF-kB, p38�± and p-p38) in LPS-activated RAW 264.7 cells was assessed by Western blot. In addition, the extract was screened for p38 MAPK inhibition using cell-free enzyme activity assay. Later, Jurkat cells were challenged for 24 h with the extract and cytotoxicity was determined by Trypan blue exclusion. After challenging RAW 264.7 and PBMCs with Myrciaria sp. extract, a slight decrease (p<0.05) on RAW 264.7 viability was observed with the maximum concentration tested (200 �¼g/mL), while PBMCs were not affected by the extract. However, PHA-stimulated PBMCs had a decreased proliferation when cultured with 200 �µg/mL extract. In addition, when both LPSactivated cells were pre- treated with the extract, there were dose-dependent decrease in TNF-�± levels (p<0.001), suggesting possible immunomodulatory and anti-inflammatory activities of the extract. Furthermore, Western blotting on RAW 264.7 cells showed that the extract was capable to inhibit LPS-induced NF-kB activation and p38 phosphorylation. Besides, Myrciaria sp. extract presented a great p38 inhibitory activity. On Jurkat cells, the ethanol extract showed cytotoxicity after 24 h, indicating a selectivity. The IC50 of the extract was 127.7 �µg/mL. The results suggest that Myrciaria sp. ethanol extract present great biological and is a potent inhibitor of p38 MAPK suggesting an action mechanism with selective activity that can be used in the development of anti-inflammatory and antileukemic drugs or phytomedicines.

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