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FIGURE 9
A proposed model showing that apigenin promotes pigmentation through the c-KIT/Raf-1/MAPK/CREB signaling pathway. Apigenin activates the c-KIT receptor, leading to phosphorylation of Raf-1. Once activated, Raf-1 phosphorylates and activates MAPK, resulting in CREB phosphorylation and subsequent nuclear translocation of CRTCs. Phosphorylated CREB, in association with CRTCs, promotes MITF transcription, which in turn induces the expression of Tyrosinase, Rab27a, and Cdc42. This cascade of events drives melanosome maturation and transport. Tyrosinase, TRP-1, and TRP-2 are key regulators of melanosome maturation. Cdc42 facilitates dendrite extension and filopodia formation, while Rab27a interacts with its effectors, Mlph and Myosin Va, to regulate actin-dependent melanosome transport and anchoring to the plasma membrane. c-KIT, cellular-KIT; Raf-1, rapidly accelerated fibrosarcoma-1; MAPK, mitogen-activated protein kinase; CRTC, CREB-regulated co-activator; CREB, cAMP response element-binding protein; MITF, Melanocytes inducing transcription factor; Cdc42, cell division cycle 42; Rab27a, Ras-related protein Rab-27a; TRP-1, tyrosinase-related protein-1; TRP-2, tyrosinase-related protein-2.