Functional peptides from the Thai medicinal plant Curcuma wanenlueanga suppress tyrosinase activity and melanin production

Excess melanin production leads to hyperpigmentation with psychological and cosmetic effects. Tyrosinase, key in melanin synthesis, is a target for treatment. This study explores tyrosinase inhibition by peptides from Curcuma wanenlueanga rhizomes. Papain was used to hydrolyze the crude proteins from rhizomes to obtain hydrolysates which underwent fractionation to acquire fractions of differing molecular weight. The most effective inhibitory action to counter tyrosinase was observed for the < 1 kDa fraction, for which the IC 50 value was 16.75 ± 1.71 µg/mL. Reverse-phase high-performance liquid chromatography (RP-HPLC) was performed to isolate the bioactive peptides VY-8 (VAPVSLSY) and FF-6 (FDNSYF). Both exhibited the competitive inhibition of tyrosinase, recording values for Ki of 1.44 ± 0.07 mM and 1.85 ± 0.09 mM respectively, while the molecular docking findings were indicative of strong binding affinities. There were strong interactions between the peptides and key tyrosinase residues in the form of hydrogen bonds and hydrophobic interactions, from which the possibility of powerful enzyme inhibition can be inferred. Melanin synthesis could be decreased by 40 % and 30 % in vitro by VY-8 and FF-6 respectively, when tested in α-MSH-stimulated B16F10 melanoma cells at concentrations considered non-cytotoxic. Other genes and proteins related to melanogenesis were also notably downregulated by both peptides according to both quantitative PCR analysis and Western blot results. An in vivo zebrafish toxicity assay showed VY-8 had no significant effect on cell death, while 50 μM reduced melanin content. These peptides have potential for safe and sustainable hyperpigmentation treatment in cosmetics and pharmaceuticals. Peptides from Curcuma aurantiaca rhizomes were identified as potent tyrosinase inhibitors. VY-8 and FF-6 reduced melanin synthesis in B16F10 cells and showed no significant toxicity, highlighting their potential for safe and sustainable hyperpigmentation treatment in cosmetics and pharmaceuticals. • Peptides VY-8 and FF-6 from Curcuma aurantiaca inhibit tyrosinase competitively. • VY-8 and FF-6 reduce melanin production in B16F10 cells without cytotoxicity. • Strong binding between peptides and tyrosinase is confirmed by molecular docking. • No significant toxicity in zebrafish, suggesting safe cosmetic and pharmaceutical use.