Antibacterial effects of extracts obtained from plants of Argentina: Bioguided isolation of compounds from the anti-infectious medicinal plant Lepechinia meyenii. (15th July 2019)

• Record Type: Journal Article
• Authors: Chabán, Macarena Funes; Karagianni, Catherine; Joray, Mariana Belén; Toumpa, Dimitra; Sola, Claudia; Crespo, María Inés; Palacios, Sara María; Athanassopoulos, Constantinos M.; Carpinella, María Cecilia
• Is Part Of: Journal of ethnopharmacology. Volume 239(2019)
• Publication Date: 2019-07-15
• Subjects: Antibacterial activity -- Plant extracts -- Abietanes -- Staphylococcus aureus -- Methicillin-resistant Staphylococcus aureus (MRSA); Carnosol -- Rosmanol -- Carnosic acid -- Carnosic acid-γ-lactone -- 20-Methyl carnosate -- 11, 12-O-Diacetylmethyl carnosate -- 11, 12-O-Diacetylcarnosic acid; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2019.111930
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: The mostly native species from Argentina are used in traditional medicine generally for the treatment of pain and inflammation, respiratory, gastro-intestinal and urinary disorders and as antiseptics. Aim of the study: Since these ailments may be associated with bacterial infections and that it is necessary to discover alternative compounds with antibacterial activity, 69 extracts from these plants were screened for their activity against pathogenic bacteria. The most effective extract was then submitted to bioguided isolation to obtain the compounds responsible for this activity. Materials and methods: Extracts and fractions were screened using agar dilution, and compounds using microbroth dilution methods. A large panel of pathogenic bacteria was used, especially methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA). Bioguided fractionation was performed using successive chromatographic techniques, while the chemical structures of the isolated compounds were determined by nuclear magnetic resonance (NMR). Additionally, a series of derivatives of the most active compound were prepared in order to study the chemical features required for achieving the antibacterial effect. Results: Lepechinia meyenii (Walp.) Epling (Lamiaceae) extract showed itself the most effective, with minimum inhibitory concentration (MIC) against Gram positive and negative bacteria ranging from 62.5 to 500 μg/mL, and showing better activity on MRSA than on MSSA. Activity-guided fractionation yielded the abietanes carnosol (1 ), rosmanol (2 ) and carnosic acid (3 ) as active principles, with MICs ranging from 15.6-31.2, 15.6–62.5 and 7.8–15.6 μg/mL, respectively against 15 MRSA strains, and 15.6–31.2, 31.2–62.5 and 7.8–15.6 μg/mL, respectively against 11 MSSA strains, maintaining higher activity against the resistant bacteria, as does the extract. In addition, Enterococcus faecalis was sensitive to 1 –3 with MICs of 15.6–62.5 μg/mL. The structure activity analysis showed that 12-OH is necessary for remarkable activity, but methylation in C-20 significantly increased this, as observed with 20-methyl carnosate (5 ) displaying the greatest effect, even more so than 3, with MICs of 3.9 μg/mL against all the tested MRSA and 3.9–7.8 μg/mL against the MSSA. Conclusions: The results of this study contribute to validate the traditional antibacterial use of species native to Argentina, particularly of L. meyenii . The chemical structures of the compounds obtained may aid the design of antibacterial agents, especially those effective against MRSA. Graphical abstract: Image 1