# Metabolomics, Molecular Networking and Phytochemical Investigation of Psiadia dentata (Cass.) DC., Endemic to Reunion Island: Discovery of Novel Bioactive Molecules

## TL;DR

This study explores the chemical composition of Psiadia dentata, a plant from Reunion Island, and identifies new bioactive compounds with antiplasmodial and anti-inflammatory properties.

## Contribution

The study discovers nine new diterpenes and one new coumarin from P. dentata, validated through metabolomics and molecular networking.

## Key findings

- Two methoxylated flavonoids and one coumarin are linked to antiplasmodial and anti-inflammatory activities.
- Twenty-five compounds were annotated, including nine new diterpenes and one new coumarin.
- Compounds 1, 7, 26, and 27 showed antiplasmodial activity, while compounds 7, 26, 27, 31, and 32 exhibited anti-inflammatory effects.

## Abstract

The genus Psiadia (Asteraceae), widely distributed in Madagascar and the Mascarene Islands (Mauritius, La Réunion, Rodrigues), is traditionally used to treat bronchitis, asthma, colds, abdominal pain, and other inflammatory disorders. However, few studies have scientifically validated these traditional medicinal uses. To assess P. dentata as a valuable source of bioactive natural products, a combined 1H NMR-based metabolomic, molecular networking, and phytochemical study was conducted. Multivariate analysis (PLS-DA) of crude extracts from Psiadia species collected on Reunion Island enabled rapid discrimination of active extracts from P. dentata and revealed two methoxylated flavonoids and one coumarin as metabolites correlated with its antiplasmodial and anti-inflammatory activities. Additionally, UHPLC-DAD-ESI-QTOF-MS/MS molecular networking approach enabled detailed chemical profiling of this species, allowing the annotation of 25 compounds (1–25) in this species. Subsequent phytochemical investigation of P. dentata leaves led to the isolation and identification of 25 metabolites, including nine new diterpenes (26–34), one new coumarin (35), and 15 known compounds (1–8, 11, 18, 19 and 36–39) from the diterpenoid, flavonoid, and coumarin families. The structures of the new compounds were elucidated using spectroscopic methods, including extensive 1D and 2D NMR and HRESIMS analyses. Biological evaluation of the isolated compounds showed that compounds 1, 7, 26 and 27 showed antiplasmodial activity against Plasmodium falciparum (3D7 strain, IC50 = 7.25–13.46 μM). Compounds 7, 26, 27, 31 and 32 inhibited nitric oxide production (IC50 = 0.87–27.71 μM), indicating potential anti-inflammatory effects. Only compound 1 displayed moderate cytotoxicity against HepG2 and HT29 cancer cell lines (IC50 = 25.67 and 18.35 μM, respectively).