Giant Centella asiatica attenuates UVB-induced photoaging-related responses and identifies rimanoside as a candidate water-soluble marker constituent

Centella asiatica (CA) is widely used to support skin health, yet heterogeneous sourcing and cultivation conditions can cause batch-to-batch variability in phytochemical profiles, complicating reproducible evaluation and standardized development. Moreover, anti-photoaging-related activity may be modest or inconsistent when aqueous extraction is applied, highlighting the need for cultivars that retain activity under water-based processing. In this study, a newly registered cultivar, Giant Centella asiatica (GCA), was compared with conventional CA for its anti-photoaging-related activity and associated mechanism under UVB-induced conditions. Water extracts of GCA and CA were assessed for chemical antioxidant capacity and total phenolic/flavonoid contents, and their effects on UVB-induced matrix metalloproteinase-1 (MMP-1)-related responses were examined in HaCaT keratinocytes using western blotting and AP-1/MMP-1 promoter luciferase assays. Under the present assay conditions, UVB increased MMP-1 protein levels by approximately 16-fold, and GCA reduced the UVB-induced signal by 74% at 20 μg/mL, whereas CA showed only 5% inhibition at the same concentration. Activity of GCA was further supported in a 3D human skin equivalent model by assessing UVB-driven MMP-1 levels and collagen-associated tissue changes. GCA showed higher chemical radical-scavenging capacity and higher phenolic and flavonoid contents than CA, and it more effectively reduced UVB-induced MMP-1-related responses, accompanied by reduced phosphorylation of c-Raf, MEK1/2, and ERK and by decreased AP-1/MMP-1 transactivation. In the 3D skin model, GCA attenuated UVB-induced MMP-1 upregulation and collagen-associated tissue changes. LC/MS-MS-guided isolation coupled with NMR identified rimanoside, a water-soluble trisaccharide and candidate marker constituent, which dose-dependently inhibited UVB-induced MMP-1 expression (IC 50 : 20.89 μM) and was associated with reduced ERK phosphorylation under the present assay conditions. Quantitative analysis further showed that rimanoside was present at a higher level in GCA than in CA under identical extraction conditions. Overall, GCA showed stronger anti-photoaging-related activity than CA under the present in vitro and 3D skin-equivalent model conditions, and rimanoside may serve as an active water-soluble constituent and candidate marker compound for future standardization of GCA. Further phytochemical standardization and in vivo validation remain necessary.