Anti-Acetylcholinesterase and Synergistic Antifungal Activities of Selected Salvia Species: Correlation with Metabolic Profiles

Abstract

Salvia species are known for their anti-fungal and anti-acetylcholinesterase (AChE) activity. Metabolomics is defined as a comprehensive quantitative and qualitative analysis of large-scale metabolites. In this study, besides determining anti-acetylcholinesterase and synergistic antifungal activities of selected Salvia species (S. cryptantha, S. tchihatcheffii, S. officinalis, S. virgata), the metabolite profiles were clarified and correlation analyzes between the activity results and profiles were carried out. Aerial parts of all plant materials were extracted by methanol to determine the metabolic profile by using GC-MS (Gas Chromatography-Mass Spectrometry) and LC-QTOF-MS (Liquid Chromatography Quadrupole Time of Flight Mass Spectrometry). Also, Ellman's spectrophotometric method for anti-acetylcholinesterase activity and the checkerboard method for synergistic antifungal activity between extracts and fluconazole were performed. 295 known and 1408 unknown metabolites were detected in GC-MS while 346 known and 69008 unknown metabolites in LC-QTOF-MS. S. cryptantha, S. tchihatcheffii, S. officinalis, and S. virgata demonstrated inhibitory activities on AChE with the ratio of 32.72%, 5.9%, 43.96%, and 12.1% at the concentration of 200 µg/m and a synergism was found for all Salvia sp. against Candida tropicalis ATCC 750 strain with the FICI values of 0.28, 0.15, 0.10, 0.5 respectively. In addition, as a result of correlation analysis, 73 metabolites positively and 31 metabolites negatively correlated with anti-acetylcholinesterase activity, while 18 metabolites positively, and 117 metabolites negatively correlated with synergistic activity were found. All Salvia species exhibited synergic activity with fluconazole while having weak AChE inhibitory activity. Combining natural products with synthetic drugs is important in order to increase efficacy. At the same time, herbal products must be used carefully at the point of herb-drug interactions. Further studies are needed to investigate active metabolites according to correlation results.

Keywords

• Acetylcholinesterase inhibitory activity
• Metabolomics
• Salvia
• Synergism
• Candida

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