Gingerols and their derivatives from ginger oleoresin and the anti-melanogenic effect in IBMX-stimulated B16F10 melanoma cells

Ginger (Zingiber officinale Roscoe), a widely used culinary and medicinal plant, has recently gained significant attention for its whitening properties. While gingerols are the primary components of ginger, the whitening effects of their numerous, structurally similar gingerols remain underexplored, particularly with insufficient structure-activity relationship (SAR) analyses. This study aimed to comprehensively investigate the anti-melanogenic effects and SAR of diverse gingerols and their derivatives. Thirty-five gingerols and their derivatives were isolated from ginger oleoresin, including two rare monoterpene-gingerol conjugates (1-2), two unreported isogingerols (3-4), and one shogaol derivative (5). Compounds 6-9 were isolated from a natural source for the first time. Structural elucidation via spectroscopic analysis, specific rotation, and electronic circular dichroism confirmed their structures and configurations, with zingerol A (1) featuring an unprecedented 1-phenyl-2-geranyl-decane scaffold. Twenty-five isolates (1-2, 4-17, 19-21, 23, 25-26, and 32-34) demonstrated dose-dependent inhibition of melanogenesis in B16F10 cells. Shogaols (19-21) exhibited equivalent anti-melanogenic activity to hydroquinone at ≤ 2.5 μM. SAR studies revealed that geranyl substitution at C-2 and aliphatic chain elongation enhanced the bioactivity, with the C-3 carbonyl group serving as a critical pharmacophore.

Anti-melanogenic; Ginger oleoresin; Gingerols; Zingiber officinale; Zingiberaceae.