Polianthes tuberosa L. Extract suppresses melanogenesis through concurrent Inhibition of cAMP/CREB and MAPK signaling pathways.

Ultraviolet (UV) radiation is a primary environmental stimulus for skin hyperpigmentation. Polianthes tuberosa L. (PT), rich in polyphenols and flavonoids, possesses antioxidant and anti-inflammatory properties, yet the anti-melanogenic mechanism of the PT extract (PTE) remains unexplored. Network pharmacology revealed nuclear factor erythroid-derived 2-like 2, superoxide dismutase 1, nuclear factor kappa B subunit 1, and interleukin-6 as core targets, suggesting that PTE may coordinately modulate oxidative stress and inflammation. Consistent with this prediction, PTE dose-dependently suppressed UV-induced intracellular reactive oxygen species generation in immortalized human keratinocyte cell line (HaCaT). Furthermore, PTE not only inhibited the UV-induced release of inflammatory cytokines and paracrine melanogenic factors in HaCaT cells, but also mitigated UV-induced collagen reduction in fibroblasts. In the mouse melanoma cell line B16F10, the PTE significantly suppressed melanogenesis and tyrosinase activity (p < 0.001). Integration of transcriptomic and proteomic data provided a complementary view of molecular regulation at both the messenger RNA and protein levels. This convergent evidence indicated that PTE acts as a concurrent inhibitor of the cyclic adenosine monophosphate (cAMP)/protein kinase A/cAMP-response element binding protein and mitogen-activated protein kinase signaling axes, as validated by quantitative polymerase chain reaction and western blot analyses. This dual inhibition led to the downregulation of microphthalmia-associated transcription factor and its downstream melanogenic enzymes. Our findings underscore the potential of PTE as a multifaceted, natural whitening agent for cosmetic applications.