AUTHOR=Kerkoub Neila , Panda Sujogya Kumar , Yang Ming-Rong , Lu Jing-Guang , Jiang Zhi-Hong , Nasri Hichem , Luyten Walter 

TITLE=Bioassay-Guided Isolation of Anti-Candida Biofilm Compounds From Methanol Extracts of the Aerial Parts of Salvia officinalis (Annaba, Algeria)

JOURNAL=Frontiers in Pharmacology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.01418

DOI=10.3389/fphar.2018.01418

ISSN=1663-9812

ABSTRACT=<p><italic>Salvia officinalis</italic> is frequently used in traditional Algerian medicine to treat diverse microbial infections, including oral and vaginal candidiasis. The aerial parts of <italic>S. officinalis</italic> collected in Annaba, Algeria were extracted in parallel by maceration with four solvents viz. hexane, acetone, methanol and water. All the extracts were tested <italic>in vitro</italic> against several <italic>Candida</italic> species: <italic>C. albicans, C. glabrata</italic>, and <italic>C. parapsilosis</italic>. Furthermore, the activity against biofilm-forming <italic>C. albicans</italic> 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 <italic>n</italic>-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 BIC<sub>50</sub> 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 <italic>Candida</italic>. Further studies of the bioactive compounds in an <italic>in vivo Candida</italic> biofilm model are required to validate their clinical potential as antifungals.</p>