Lactic acid inhibits melanin synthesis by regulating histone H3 lactylation and suppressing tyrp1 transcription in B16 melanoma cells.

Lactic acid, a widely distributed metabolic intermediate, exhibits superior permeability and mild acidity, making it a common reagent in skincare products. Lactic acid could significantly reduce melanin synthesis both in vitro and in vivo. However, the underlying molecular mechanisms remain less clear. To reveal the molecular mechanism by which lactic acid inhibits melanin synthesis through epigenetic pathways, proteins with significantly increased levels of lactylation modifications after lactic acid addition were identified through HPLC-MS/MS. Key genes affected by lactic acid addition were identified using ChIP-seq, and validated through qPCR and Western blot analyses. We reveal that lactic acid could promote protein lactylation in a dose-dependent manner in B16 cells. HPLC-MS analysis revealed that histone H3 showed the most significant increase in lactylation following lactic acid treatment. Through ChIP-seq analysis, we observed that lactylated histone H3 binding at the promoter region of the key melanogenesis gene, Tyrp1, significantly decreased after lactic acid treatment. This was accompanied by a notable reduction in Tyrp1 protein level. Our findings suggest that protein lactylation play a crucial role in lactic acid induced melanin synthesis inhibition.