Synergistic impact of arbutin and kaempferol‑7‑O‑α‑l‑rhamnopyranoside from Nephelium lappaceum L. on whitening efficacy and stability of cosmetic formulations

Four flavonoid glycosides, namely quercetin-3-O-rhamnoside (1), kaempferol-3-O-β-d-glucopyranosyl
(2), kaempferol-7-O-α-l-rhamnopyranoside (3), and kaempferol-3-O-β-d-glucopyranosyl-7-O-α-lrhamnopyranoside
(4), from Nephelium lappaceum L. seeds were evaluated for their efficacy against
melanin inhibition in B16F10 melanoma cells and tyrosinase inhibition. Among them, kaempferol-7-
O-α-l-rhamnopyranoside (3) displayed the highest potency in both activities without any significant
cytotoxicity. The combination of compound 3 and arbutin in specific proportions demonstrated a
synergistic effect (CI < 1) in inhibiting melanin production in B16F10 cells and tyrosinase inhibition.
Additionally, a cosmetic formulation containing compound 3 and arbutin as active ingredients
exhibited favorable stability under accelerated storage conditions. Quantitative analysis indicated
that compound 3 and arbutin levels in the formulation were above 90% after one month of storage.
Determination of the formulation’s shelf life using the Q10 method, estimating it to be around
5.2 months from the date of manufacture. The synergy between arbutin and kaempferol-7-O-α-
l-rhamnopyranoside (3) extracted from N. lappaceum substantially enhances both the whitening
effectiveness and the stability of cosmetic formulations.