Prenylated flavonoid-enriched fraction from Maclura tinctoria shows biological activity against Staphylococcus aureus and protects Galleria mellonella larvae from bacterial infection

Abstract

Background The Atlantic Forest biome extends along the entire Brazilian coast and is home to approximately 20,000 plant species, many of which are endemic; it is considered one of the hotspot regions of the planet. Several of these species are sources of natural products with biological activities that are still unknown. In this study, we evaluated the antimicrobial activity of 90 extracts derived from native Atlantic Forest tree species against Staphylococcus aureus , an important human and veterinary pathogen. Methods Extracts from native Atlantic Forest tree species were evaluated for their antimicrobial activity against S. aureus by in vitro standard methods. Phytochemical fractionation of the extract from Maclura tinctoria was performed by liquid-liquid partitioning. LC-DAD-ESI-MS was used for identification of constituents in the most active fraction. Damage of cells and alterations in the permeability of cell membrane were determined by atomic force microscopy (AFM) and crystal violet uptake assay, respectively. In vivo antimicrobial activity was evaluated using Galleria mellonella larvae infected with S. aureus with survival data collected using the Kaplan-Meier method. Results Among the organic or aqueous extracts tested here, 26 showed biological activity. Eight species showed relevant results, with a minimum inhibitory concentration (MIC) below 1 mg/mL. Antibacterial activity was registered for three species for the first time. An organic extract from Maclura tinctoria leaves showed the lowest MIC (0.08 mg/mL). Fractionation of this extract by liquid-liquid partitioning led to obtaining fraction 11FO d with a MIC of 0.04 mg/mL. This fraction showed strong activity against veterinary S. aureus isolates and contributed to the increased survival of Galleria mellonella larvae infected with S. aureus ATCC 29213. The bacterial surface was not altered by the presence of 11FO d, and no cell membrane damage was detected. The LC-DAD-ESI/MS analyses identified prenylated flavonoids as the major constituents responsible for the antibacterial activity of this active extract. Conclusion A fraction enriched in prenylated isoflavones and flavanones from M. tinctoria showed in vitro and in vivo efficacy as antistaphylococcal agents. These findings justify the need for further research to elucidate the mechanisms of action of these compounds.

Prenylated Flavonoids with Potential Antimicrobial Activity: Synthesis, Biological Activity, and In Silico Study

“…This coincides with those reported in the literature, where prenylated flavanones show better activity than flavones [ 28 , 29 ]. The position of the hydroxyl substituents, as well as that of the prenyl group, appears to be important in the inhibitory activity of bacterial growth, observing that derivatives with OH at positions C-5, 7, and 4′ show better inhibitory activity, as well as the presence of prenyl groups in the C6 and C8 positions of Ring A, as previously reported [ 30 , 31 , 32 ]. Araya–Coultier et al (2018) showed that the position of the prenyl group affects the antimicrobial activity of flavonoids, when comparing the effect of lupiwighteone (5,7,4′-trihydroxy-8-prenylisoflavone) and wighteone (5,7,4′-trihydroxy-6-prenylisoflavone), on the Gram-positive strain L. monocytogenes .…”

Molecular bioprospecting of plant extracts: Experience report of the BIOPROS/UFV group in the search for antitumor compounds

“…It is the aim of the BIOPROS group that has been implemented a large-scale project to produce and test extracts from the Atlantic Forest trees, where species are still rarely studied for their biological activity. The BIOPROS Extract Library is also screened in other biological targets such as antibacterial [24,25] , Anticholinesterase inhibitor [26] , Insecticidal [27] , and phytonematode control [28] .…”

Cellular Responses and Targets in Food Spoilage Yeasts Exposed to Antifungal Prenylated Isoflavonoids

“…Other studies have reported cytosolic presence and activity of diprenylated (iso)flavonoids ( 13 , 14 ). das Chagas Almeida et al ( 15 ) demonstrated that the antimicrobial activity of a plant extract rich in mono- and diprenylated (iso)flav(an)ones was exerted without permeabilization of the PM of Staphylococcus aureus (assessed through crystal violet uptake at extract concentrations up to 8× MIC) or any disruption of the cell surface (as evidenced by atomic force microscopy at the MIC), suggesting alternative targets in bacteria.…”