Eriobotrya japonica (Loquat) Leaf Extract: An Integral In Vitro and In Ovo Approach to Antimelanoma Potential and...

Melanoma continues to be one of the most challenging diseases in oncology, given its aggressiveness and increased resistance to existing therapies. Therefore, the identification of novel therapeutic strategies is of considerable interest, with medicinal plants representing a promising source of bioactive compounds. In the present study, the phytochemical profile and the in vitro biological activity of a lyophilized aqueous leaf extract of Eriobotrya japonica (Thunb.) Lindl. cultivated in Romania were investigated. The extract was characterized by determining the total phenolic content, antioxidant capacity, and polyphenolic composition using UHPLC-MS/MS. Its cytotoxic potential and cytocompatibility were evaluated at concentrations of 50, 100, 200, 300, 400, and 500 µg/mL in two human melanoma cell lines (RPMI 7951 and A375) and in the human keratinocyte cell line HaCaT. Cell viability and morphological alterations were assessed in all three cell lines. Subsequently, the study focused on assessing the effects of the extract on melanoma cells by evaluating lysosome integrity and the intracellular production of reactive oxygen species (ROS). The impact on mitochondrial membrane potential, as well as on mitochondrial and nuclear morphology, was also determined. Finally, the HET-CAM test was carried out to assess the extract's preliminary irritant potential at 500 µg/mL. The results showed that the extract presented a high content of phenolic compounds and high antioxidant capacity. The most abundant compounds in the extract were chlorogenic acid, rutin, 3,5-dihydroxybenzoic acid/3,4-dihydroxybenzoic acid, and p-coumaric acid/trans-p-coumaric acid. With regard to biological activity, the treatment induced low cytotoxicity in HaCaT cells including at 500 µg/mL. At the same time, it produced a dose-dependent reduction in the viability of melanoma cells, accompanied by impaired lysosomal integrity. It was observed that the extract increased ROS levels and mitochondrial membrane depolarization, thereby inducing morphological changes at the mitochondrial and nuclear levels. However, across all performed assays, the most pronounced effects were observed starting at a concentration of 300 µg/mL. The HET-CAM assay classified the extract as non-irritant at 500 µg/mL. These findings suggest that Eriobotrya japonica leaf extract exerts antimelanoma effects associated with oxidative stress and mitochondrial dysfunction while maintaining a favorable preliminary safety profile.