Abstract

Salvia officinalis is frequently used in traditional Algerian medicine to treat diverse microbial infections, including oral and vaginal candidiasis. The aerial parts of S. officinalis collected in Annaba, Algeria were extracted in parallel by maceration with four solvents viz. hexane, acetone, methanol and water. All the extracts were tested in vitro against several Candida species: C. albicans, C. glabrata, and C. parapsilosis. Furthermore, the activity against biofilm-forming C. albicans was investigated using bioassay-guided fractionation. A large-scale extract was prepared via maceration in methanol, followed by fractionation on a silica gel column using increasingly polar mixtures of n-hexane, ethyl acetate, methanol, and acetic acid as mobile phase, to yield a total of 150 fractions. Two major active fractions (F-31 and F-39), were further separated by HPLC, resulting in several active chromatographic peaks. Carnosol and 12-methoxy-trans-carnosic acid were isolated as two major active compounds, and identified by a combination of NMR and mass spectrometry. The biofilm inhibitory concentration showed that 12-methoxy-trans-carnosic acid is more effective than carnosol with BIC50 values of 94 μM (95% confidence interval, 78.9–112.1 μM) and 314 μM (95% confidence interval, 200.7–491.2 μM), respectively. The present study supports the traditional use of sage in the treatment of various fungal infections caused by Candida. Further studies of the bioactive compounds in an in vivo Candida biofilm model are required to validate their clinical potential as antifungals.

Highlights

  • Over the past decades, the incidence of fungal infections has dramatically increased, especially for systemic ones, due to a combination of reasons: the growing use of invasive medical devices, and the increased use of broad-spectrum antimicrobial as well as immunosuppressive therapies (Kojic and Darouiche, 2004; Pfaller et al, 2014; Nett and Andes, 2015)

  • All these extracts were tested for antifungal activity against different Candida species (Table 2)

  • The methanol extract was most effective against both biofilm and liquid culture of C. albicans (Figure 2)

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Summary

Introduction

The incidence of fungal infections has dramatically increased, especially for systemic ones, due to a combination of reasons: the growing use of invasive medical devices (e.g., intravascular and urinary catheters, as well as implanted prostheses), and the increased use of broad-spectrum antimicrobial as well as immunosuppressive therapies (Kojic and Darouiche, 2004; Pfaller et al, 2014; Nett and Andes, 2015). Despite advances in antifungal therapy, Candida infections continue to have a major impact on mortality and morbidity, as well as on the duration and cost of hospitalization (Tanwar et al, 2014). This situation has led pharmaceutical companies and researchers to explore new alternatives, in order to discover improved antifungal agents that satisfy efficacy, safety, and economic criteria. “Increasing trends of health organizations and pharmaceutical industries to use plants as safe and effective alternative sources of synthetic antifungals are due to major problems of slow growing and high costs of synthetic pharmaceutics, their life-threatening side effects, rapid increase in new fungal infections, and dramatic emergence of multidrug-resistant fungal pathogens.” (RazzaghiAbyaneh and Rai, 2013; Razzaghi-Abyaneh et al, 2013)

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