Identifying Key Metabolites in South African Medicinal Plants Using Dual Electrospray Ionization Metabolomics

Area of Science:

• Metabolomics
• Pharmacognosy
• Medicinal Chemistry

Background:

• South African medicinal plants are of growing interest, but advanced metabolomic analyses are underutilized.
• Acorus calamus and Lippia javanica are key species requiring detailed chemical profiling.
• Integrating dual-polarity liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) offers enhanced metabolome coverage.

Purpose of the Study:

• To apply a dual-polarity UPLC-MS/MS workflow to map the metabolomes of Acorus calamus and Lippia javanica.
• To identify and rank potential signature metabolites for antiviral drug discovery.
• To assess the cytotoxicity and in silico drug-likeness of identified metabolites.

Main Methods:

• Untargeted UPLC-MS/MS analysis using both positive (ESI+) and negative (ESI-) ionization modes.
• HEK293T cytotoxicity screening and SwissADME analysis for in silico drug-likeness.
• Multivariate statistical analysis (PCA) and differential analysis to segregate species and identify significant metabolites.

Main Results:

• Dual-polarity analysis expanded metabolome coverage, with ESI- yielding more features than ESI+.
• Neither plant extract exhibited cytotoxicity.
• Differential analysis identified significant metabolites, including flavonols, iridoid glycosides, and jasmonate-pathway oxylipins, with ESI- showing a wider dynamic range.
• In vitro inhibition of SARS-CoV-2 papain-like protease (PLpro) was observed, linking chemical profiles to antiviral activity.

Conclusions:

• A dual-mode UPLC-MS/MS approach provides comprehensive metabolome coverage and safety data for South African medicinal plants.
• This method facilitates the identification of potential antiviral signature metabolites with favorable drug-likeness.
• The findings support the use of Acorus calamus and Lippia javanica for downstream antiviral research.