Identification of Antioxidant Plant Extracts and Garcinia amplexicaulis Metabolites with Ferroptosis Inhibitor-like Chemical Properties for Alternative Crop Protection

Background: Sustainable strategies to control fungal diseases are urgently needed due to the environmental and human health impacts of conventional fungicides and the rise in fungicide resistance. Ferroptosis modulation, an iron-dependent programmed cell death, could represent an alternative strategy for crop protection, although its potential for fungal disease management remains largely unexplored. Methods: The aim of this study was to run preliminary screening assays, identify plant extracts and natural products with requested chemical properties for ferroptosis inhibition, and evaluate their ability to limit Alternaria brassicicola infection. Results: The CAT-based screening of 165 plant extracts led to the identification of several antioxidant-active extracts, including Garcinia amplexicaulis (G. amplexicaulis) (bark, DCM), Garcinia kola (G. kola) (nut, DCM), Magnolia sieboldii (M. sieboldii) (leaf, MeOH) and G. amplexicaulis (leaf, MeOH). The major constituents, δ-amplexichromanol, δ-garcinoic acid, sieboldin and (−)-epicatechin, found in the most active fractions from these extracts displayed CAT activities comparable to those of the synthetic ferroptosis inhibitors ferrostatin-1 and phenoxazine. Among these compounds, δ-amplexichromanol showed detectable in vitro inhibitory activity against A. brassicicola and significantly reduced lesion development in planta, with an efficacy comparable to ferrostatin-1 and phenoxazine. The antifungal activity of G. amplexicaulis (leaf, MeOH) observed in vitro was also confirmed in planta. Conclusions: these findings highlighted δ-amplexichromanol and G. amplexicaulis (leaf, MeOH) as candidates for further investigation and supported the potential of CAT-based antioxidant screening to prioritize plant extracts for subsequent evaluation against A. brassicicola.