GNPS Molecular-Networking-Guided Isolation of New Antiphotoaging Theasaponins from Camellia chekiangoleosa Flower

Guided by the global natural products social molecular networking (GNPS) technology, a targeted phytochemical investigation on the flowers of Camellia chekiangoleosa was performed, yielding two new naturally occurring theasaponins and four new related artifacts named camelliosides K–P (1, 2, 5, 6, 9, and 13), together with eight known analogues. The chemical structures were systematically elucidated based on comprehensive NMR and MS spectroscopic analyses, combined with hydrolysis experiments for sugar moiety identification. Structurally, camellioside K (1) had a rare ketone substitution at the C-11 position, while compound 2 represents an unusual trisaccharide saponin that is rarely reported from the Theaceae family, significantly enriching the structural diversity of plant saponins derived from Camellia species. All isolated compounds exerted prominent anti-inflammatory effects by remarkably inhibiting the production of pro-inflammatory TNF-α and IL-6. Further In vitro antiphotoaging assay demonstrated that the new compounds 1 and 2 exerted remarkable protective effects against ultraviolet B (UVB)-induced photoaging damage in human fibroblasts. Both compounds markedly upregulated the production of type I collagen and downregulated the mRNA expression of matrix metalloproteinases 1 (Mmp1) and 3 (Mmp3). Notably, camelliosides K and L were verified to promote the biogenesis of mitophagosomes and lysosomes, activate PINK1–Parkin signaling consistent with a mitophagy-related response, and alleviate mitochondrial damage by elevating the protein levels of PINK1 and Parkin in UVB-stimulated fibroblasts. Collectively, this work demonstrates that the newly identified saponins from C. chekiangoleosa serve as promising natural candidates for the prevention and treatment of skin inflammation and UV-triggered photoaging diseases.