Biochemometry identifies ostruthin as pluripotent antimicrobial and anthelmintic agent from masterwort
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Julia Zwirchmayr1, Cristina D Cruz2, Ulrike Grienke1
1Department of Pharmaceutical Sciences, Division of Pharmacognosy, Faculty of Life Sciences, University of Vienna, 1090 Vienna, Austria.
Abstract:
The root extract of Peucedanum ostruthium (PO-E) was identified as a promising antibacterial source from a screening of 158 extracts against Staphylococcus aureus. It has also recently been shown to significantly decrease the survival of the nematode Caenorhabditis elegans. We used the biochemometric approach ELINA to investigate the phytochemical characteristics of the multicomponent mixture PO-E to identify the anti-infective constituent(s) targeting S. aureus and C. elegans.1H NMR spectra of PO-E-derived microfractions were correlated with their respective bioactivity data. Heterocovariance analyses unambiguously identified ostruthin as an anti-staphylococcal constituent, which potently also inhibited Enterococcus spp.. ELINA demonstrated that anthelmintic activity was due to a combinatorial effect of ostruthin and isoimperatorin. A C. elegans-based survival and motility assay confirmed that isoimperatorin, imperatorin, and verapamil modulated the susceptibility of ostruthin. The combinatorial effect of these natural products was shown in larvae studies to be related to the function of the nematodes' efflux pump.
Insights
The root extract of Peucedanum ostruthium (PO-E) contains ostruthin, an antibacterial compound effective against Staphylococcus aureus. Anthelmintic activity resulted from ostruthin and isoimperatorin, modulated by efflux pump interactions.
Area of Science:
- Phytochemistry
- Natural Products Chemistry
- Pharmacology
Background:
- Peucedanum ostruthium root extract (PO-E) shows antibacterial activity against Staphylococcus aureus.
- PO-E also exhibits significant effects on the survival of the nematode Caenorhabditis elegans.
- Identifying specific bioactive compounds within complex natural extracts is crucial for drug discovery.
Purpose of the Study:
- To identify the specific anti-infective constituents within PO-E targeting S. aureus and C. elegans.
- To elucidate the mechanisms of action for identified compounds.
- To investigate potential synergistic or modulatory effects between phytochemicals.
Main Methods:
- Biochemometric analysis using the ELINA approach.
- Correlation of 1H NMR spectra of microfractions with bioactivity data.
- C. elegans survival and motility assays.
- Analysis of nematode efflux pump function.
Main Results:
- Ostruthin was identified as the primary anti-staphylococcal constituent, also inhibiting Enterococcus spp.
- Anthelmintic activity was attributed to a combination of ostruthin and isoimperatorin.
- Isoimperatorin, imperatorin, and verapamil were found to modulate ostruthin's activity via the nematode efflux pump.
Conclusions:
- Ostruthin is a key antibacterial compound from P. ostruthium.
- The anthelmintic effect of PO-E is a result of combinatorial action involving ostruthin and isoimperatorin.
- Phytochemicals can modulate host susceptibility through mechanisms like efflux pump interaction.
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