Antioxidant, antibacterial, and antileishmanial potential of Micromeria nervosa extracts and molecular mechanism of action of the bioactive compound

Aims: This study aimed to determine the antibacterial and antileishmanial potential of Micromeria nervosa extracts. The identification of the antileishmanial compound and the study of its molecular mechanism of action have also been undertaken. Methods and results: Ethanol extract showed high polyphenol content and diethyl ether extract exhibited high DPPH scavenging and low beta-carotene bleaching activity (IC50 = 13.04 ± 0.99 and 200.18 ± 3.32 μg mL−1 , respectively). However, diethyl ether extract displayed high antibacterial activity against Gram-positive strains including methicillin-resistant Staphylococcus aureus (MIC = 31.25 μg mL−1 ), Staph. aureus ATCC6538 (MIC = 62.5 μg mL−1 ), and Listeria monocytogenes ATCC 19115 (MIC = 125 μg mL−1 ), as well as high antileishmanial activity against the promastigote forms of L. infantum and L. major (IC50 = 11.45 and 14.53 μg mL−1 , respectively). The active compound was purified using bioassay-guided fractionation and thin layer chromatography, and identified as ursolic acid using high-performance liquid chromatography coupled with a photodiode array and mass spectrometry. The purified compound was strongly inhibitory against the promastigote and amastigote forms of L. infantum and L. major (IC50 = 5.87 and 6.95 μg mL−1 versus 9.56 and 10. 68 μg mL−1 , respectively) without overt cytotoxicity against Raw 264.7 macrophage cells (SI = 13.53 and 11.43, respectively). The commercial compound (ursolic acid) showed similar activity against amastigotes and promastigotes forms of L. infantum and L. major. Moreover, its molecular mode of action against leishmaniasis seems to involve the expression of the ODC and SPS genes involved in thiol pathway. Conclusion: Extracts of M. nervosa can be considered as a potential alternative to antimicrobial and antileishmanial drugs.