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 (NFE2L2), superoxide dismutase 1 (SOD1), nuclear factor kappa B subunit 1 (NFKB1) and interleukin-6 (IL-6) as core targets. This suggests that the therapeutic mechanism of the PTE may involve the coordinated modulation of oxidative stress (via NFE2L2/SOD1) and inflammation (via NFKB1/IL-6)—two interconnected pathways that critically drive melanogenesis following UV exposure. The PTE dose-dependently inhibited UV-induced release of inflammatory cytokines and paracrine melanogenic factors in the immortalized human keratinocyte cell line. It 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. Overall design: RNA-seq of Murine B16F10 melanoma cells in control and Polianthes tuberosa L. extract-treated group