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

The genus <i>Psiadia</i> (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 <i>P. dentata</i> 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 <i>Psiadia</i> species collected on Reunion Island enabled rapid discrimination of active extracts from <i>P. dentata</i> 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 (<b>1</b>-<b>25</b>) in this species. Subsequent phytochemical investigation of <i>P. dentata</i> leaves led to the isolation and identification of 25 metabolites, including nine new diterpenes (<b>26</b>-<b>34</b>), one new coumarin (<b>35</b>), and 15 known compounds (<b>1</b>-<b>8</b>, <b>11</b>, <b>18</b>, <b>19</b> and <b>36</b>-<b>39</b>) 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 <b>1</b>, <b>7</b>, <b>26</b> and <b>27</b> showed antiplasmodial activity against <i>Plasmodium falciparum</i> (3D7 strain, IC₅₀ = 7.25-13.46 μM). Compounds <b>7</b>, <b>26</b>, <b>27</b>, <b>31</b> and <b>32</b> inhibited nitric oxide production (IC₅₀ = 0.87-27.71 μM), indicating potential anti-inflammatory effects. Only compound <b>1</b> displayed moderate cytotoxicity against HepG2 and HT29 cancer cell lines (IC₅₀ = 25.67 and 18.35 μM, respectively).