Bioactive metabolites of Lagenaria siceraria cultivated in Egypt: Insights from LC-QTOF-MS/MS metabolomic profiling and chemometric analysis.

Abstract

Lagenaria siceraria (Bottle gourd) is a nutritionally and medicinally valuable plant. However, comprehensive metabolomic profiling across different organs of the plant to uncover key bioactive metabolites linked to the broad biological activities remain unexplored. This study applied untargeted metabolomics to compare methanol extracts from five L. siceraria organs-leaves (LE), unripe fruits (UF), ripe fruits (RF), seeds (SE), and roots (RO)-employing liquid chromatography quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS), integrated with molecular networking, and chemometrics. Biological activities of the extracts were evaluated through assays measuring proteolytic enzymes inhibition, cell migration, and antioxidant activity. Ninety-eight metabolites were annotated belonging to flavonoids, phenolic acids, amino acids, fatty acids/amides, phospholipids, and sphingolipids. Hierarchical clustering and PCA revealed distinct organ-specific metabolite profiles. LE constituted higher levels of flavonoid-C-glycosides and phenolic acids, while RO and SE were richer in fatty acids and phospholipids, respectively. OPLS-DA and KEGG analyses identified key metabolic pathways associated with the tested activities. RO, LE, and SE inhibited collagenase activity (IC50 values of 200.6 ± 4.8, 335.2 ± 17.1, and 873.9 ± 44.5 μg/mL, respectively), while LE showed potent elastase inhibition (IC50 = 1.64 ± 0.08 μg/mL), enhanced SOD activity (3.22 ± 0.36 ng/mL), and superior antioxidant potential. All extracts enhanced fibroblast migration within 48 h, with SE and LE achieving increases of 99.7% and 79.8%, respectively. LC-QTOF-MS metabolomic profiling and chemometrics revealed that the inhibition of collagenase and elastase enzymes of L. siceraria organs are closely linked to the presence of flavonoid-C-glycosides, phenolic acids, amino acids, and fatty acids.