Hydroalcoholic Extract and Ethyl Acetate Fraction of Bixa orellana Leaves Decrease the Inflammatory Response to Mycobacterium abscessus Subsp. massiliense.

José Lima Viana,Cristina De Andrade Monteiro,Rafael Cardoso Carvalho,Lídio Gonçalves Lima Neto,Luís Felipe Lima Lobato,João Henrique Ghilardi Lago,Afonso Gomes Abreu,Luís Cláudio Nascimento Da Silva,Adrielle Zagmignan,Eduardo Martins De Sousa,Letícia Machado Gonçalves,Joicy Cortez De Sá

doi:10.1155/2018/6091934

Abstract

The incidence of infections caused by rapidly growing mycobacteria (RGM), especially Mycobacterium abscessus subsp. massiliense (Mabs), is increasing worldwide. Severe infections are associated with abscess formation and strong inflammatory response. This study evaluated the antimicrobial and anti-inflammatory activities of a hydroalcoholic extract (BoHE) and ethyl acetate fraction (BoEA) of Bixa orellana leaves. Antimicrobial activity was evaluated by broth microdilution to determine the minimum inhibitory (MIC) and the minimum bactericidal (MBC) concentrations. Cytotoxicity was evaluated using erythrocytes and RAW 264.7 cells. Nitric oxide (NO) was assayed in stimulated RAW 264.7 cells, and inflammatory cell migration and acute toxicity were evaluated in a Mabs-induced peritonitis mouse model. The compounds present in BoEA were identified by high performance liquid chromatography and mass spectrometry (HPLC-MS). The MIC and MBC values were 2.34 mg/mL and 37.5 mg/mL for BoHE and 0.39 mg/mL and 6.25 mg/mL for BoEA. The extracts did not induce significant toxicity in erythrocytes and RAW 264.7 cells. High levels of NO induced by Mabs were decreased by treatment with both extracts. The anti-inflammatory activity was confirmed in vivo by significant reduction of the cell migration to the peritoneum following BoHE and BoEA pretreatment. Animals treated with BoHE or BoEA did not show signs of acute toxicity in stomach, liver, and kidney. The chemical characterization of BoEA (the most active extract) revealed that kaempferol-3-O-coumaroyl glucose is its major component. The extract of B. orellana may be effective for treating infections caused by Mabs.

Highlights

The Mycobacterium abscessus complex is formed by M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii [1, 2]
This study evaluated the antimicrobial and antiinflammatory activities of BoHE and BoEA leaf extracts of B. orellana, which is a plant widely used in Brazilian folk medicine to treat Mycobacterium infections and other inflammatory disorders [14]
The BoHE showed a MIC of 2.34 mg/mL and the minimum bactericidal (MBC) was 37.5 mg/mL, while MIC found in BoEA was 0.39 mg/mL and the MBC was 6.25 mg/mL

Summary

Introduction

The Mycobacterium abscessus complex is formed by M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii [1, 2]. Acquired macrolide resistance may develop during treatment of M. abscessus subsp. Previous studies have described Bixa orellana ( known as urucum) as a source of antimicrobial agents. The seeds of this plant are currently used in folk medicine to treat heart disease, gastrointestinal problems, respiratory infections, burns [14], diabetes, skin infections, fever, measles, gonorrhea, diarrhea, and asthma [15]. The antimicrobial action [16] and antioxidant activity [17] of the methanolic extract of B. orellana seeds and leaves against Gram-positive bacteria (e.g., S. mutans and S. sanguinis) have previously been described. The antimalarial activity of essential oils and root extracts [18] and the anti-inflammatory effects of aqueous extracts of the leaves [19, 20] have been reported

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