In vitro activity of Brazilian medicinal plants, naturally occurring naphthoquinones and their analogues, against methicillin-resistant Staphylococcus aureus

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Abstract

Fourteen extracts from Brazilian traditional medicinal plants used to treat infectious diseases were used to look for potential antimicrobial activity against multiresistant bacteria of medical importance. Staphylococcus aureus strains were susceptible to extracts of Punica granatum and Tabebuia avellanedae. The minimum inhibitory concentrations (MICs) of the total extracts and of additional fractions of these plants were determined by employing strains of methicillin-resistant (MRSA) and -sensitive (MSSA) S. aureus, including isolates of the PFGE clone A, which is prevalent in Brazil and two ATCC reference strains. A mixture of ellagitannins isolated from P. granatum and two naphthoquinones isolated from T. avellanedae demonstrated antibacterial activity against all S. aureus strains tested. Semi-synthetic furanonaphthoquinones (FNQs) showed lower MICs than those exhibited by natural occurring naphthoquinones. The results indicate that these natural products can be effective potential candidates for the development of new strategies to treat MRSA infections.

Introduction

The use of higher plants and preparations made from them to treat infections is an age-old practice in a large part of the world population, especially in developing countries, where there is dependence on traditional medicine for a variety of diseases [1]. Interest in plants with antimicrobial properties has revived as a consequence of current problems associated with the use of antibiotics [2], [3].

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) isolates have increased greatly during the last decades in hospital [4], [5] and the community [6]. The epidemic clones characterized by Pulsed Field Gel Electrophoresis (PFGE) are capable of rapid spread [7]. In Brazil, the PFGE clone A has been shown to be prevalent in several hospitals [5], [8].

In vitro antimicrobial screening permits the selection of crude plant extracts with potentially useful properties to be used for further chemical and pharmacological studies. The present report is one of a series of studies aimed at the identification of Brazilian plants with antibiotic properties. The 14 botanical species selected here for antimicrobial activity testing against hospital isolates of S. aureus, including MRSA strains, are used in traditional medicine for the treatment of gastrointestinal, respiratory, urinary and skin infections. The quinones tested were obtained within a research program of our laboratory that studies the synthesis and evaluation of rare natural quinones from the Brazilian flora and their synthetic analogues against tropical endemic diseases [9].

Section snippets

Plant material extraction and fractionation

Fourteen different plant species and plant fractions were used as shown in Table 1. The plants were extracted by maceration in ethanol for 2 days at room temperature and the process was repeated twice. The total ethanolic extracts (te) were concentrated in a rotational evaporator under reduced pressure and the residues were then successively partitioned between water (w) and n-hexane (h), followed by chloroform (c) or dichloromethane (d), ethyl acetate (ea) and n-butanol (b). The solutions were

Preliminary evaluation of antibacterial activity

Among the total ethanolic extracts and fractions tested by the disk diffusion method, the P. granatum fruit-pericarp and the wooden part of T. avellanedae extracts and fractions presented antibacterial activity against all S. aureus strains tested. The highest activities were found in the ethyl acetate fraction of P. granatum (PG ea) and in the hexane (TA h) and chloroform (TA c) fractions of T. avellanedae, as well as in the naphthoquinone α-xyloidone II. Lapachol, the major naphthoquinone

Discussion

Infections caused by methicillin-resistant S. aureus (MRSA) have increased over the last years. The percentage of MRSA isolated in hospitals and reported to the NNIS system ranged from 15 to 45% in 1991 [2]. By 1990, MRSA strains represented between 38 and 78% of all S. aureus strains isolated in tertiary hospitals in Brazil [3]. Its resistance has been related to the predominance of the single PFGE clone A of MRSA isolated from Brazilian hospitals [5], [8]. The presence of this prevalent clone

Acknowledgements

We are grateful to Dr Benjamin Gilbert, Dr Walter R. Oeleman and Dr Fernando S. Cruz for their comments and suggestions. This study was supported by grants from CNPq, FUJB, FAPERJ and PRONEX (Brazil).

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