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PP-19

Investigation into the anti-melanogenic activity and underlying mechanism

of natural products from Zingiberaceae plant

1
1
#,1
Hsin-Ya Yu (游新雅), Y u -Chen Chen (陳禹臻), Horng-Huey Ko (柯宏慧), Shuen-Shin
1,3
Yang (楊舜心), Hsun-Shuo Chang (張訓碩), Yih-Fung Chen (陳宜芳)* ,1,3
2

1 School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Taiwan
2 Department of Pharmacy, Chia Nan University of Pharmacy and Science, Taiwan
3 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University,
Taiwan
* E-mail: yihfungchen@kmu.edu.tw

Abstract
Melanin is the photoprotective cellular pigment that contributes to the color of the skin and
hairs. Hyperpigmentation, the overproduction of melanin, not only increases the risk of
melanoma but also leads to mental stress. Currently used depigmentation agents still have side
effects of skin irritation or irreversible hypopigmentation, highlighting the needs for novel and
safer alternatives. Previous studies have revealed the anti-melanogenic potential of
Zingiberaceae plants. Therefore, we aimed to identify effective anti-melanogenic compounds
from rhizome of Zingiberaceae plant using melanocyte-based anti-melanogenesis platform and
investigate its anti-melanogenic mechanism through skin cell models, in vitro enzyme assays,
and in silico molecular docking. Among the seven compounds isolated from Zingiberaceae
plant, the flavonoid compound 6 ameliorated α-MSH-induced melanin content and tyrosinase
activity in B16F10 melanocytes at non-cytotoxic concentrations. Additionally, compound 6
exhibited strong binding affinity with mushroom tyrosinase (PDB ID: 2y9x) without tyrosinase
enzyme inhibitory effect. Furthermore, compound 6 decreased α-MSH-induced tyrosinase-
related proteins 1 (TRP1) but not tyrosinase and tyrosinase-related proteins 2 (TRP2) protein
expression in B16F10 melanocytes. Additionally, compound 6 mitigated the dendrite formation
of melanocytes without influencing melanosome transport and distribution. These results
demonstrated that compound 6 from Zingiberaceae plant inhibits melanogenesis in B16F10
melanocytes by downregulating TRP1 protein level without directly affecting tyrosinase
enzyme activity, tyrosinase protein level, or melanosome transport, empathizing its potential as
a depigmenting agent for cosmetic or therapeutic applications.

Keywords: Zingiberaceae; Anti-melanogenesis; Tyrosinase; Molecular docking