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Germacrone, isolated from Curcuma wenyu**, inhibits melanin synthesis through the regulation of the MAPK signaling pathway

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Abstract

Abnormal melanin synthesis causes hyperpigmentation disorders, such as chloasma, freckles, and melanoma, which are highly multiple and prevalent. There were few reports on the anti-melanogenic effect of Curcuma wenyu** Y.H. Chen et C. Ling, and the bioactive compound has not been elucidated as well. The study aims to investigate the anti-melanogenic effect of C. wenyu**, and identify the bioactive compound, and further explore its underlying mechanism. Our results showed that the Petroleum ether fraction extracted from C. wenyu** rhizome had a significant anti-melanogenic effect, and germacrone isolated from it was confirmed as the major bioactive compound. To our data, germacrone significantly inhibited tyrosinase (TYR) activity, reduced melanosome synthesis, reduced dendrites formation of B16F10 cells, and melanosome transport to keratinocytes. Moreover, germacrone effectively decreased the hyperpigmentation in zebrafish and the skin of guinea pigs in vivo. Western-blot analysis showed that germacrone down-regulated the expression of TYR, TRP-1, TRP-2, Rab27a, Cdc42, and MITF proteins via the activation of the MAPK signaling pathway. Taken together, germacrone is an effective bioactive compound for melanogenesis inhibition. Our studies suggest that germacrone may be considered a potential candidate for skin whitening.

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Abbreviations

TYR:

Tyrosinase

TRP-1:

Tyrosinase-relative protein 1

TRP-2:

Tyrosinase-relative protein 2

MITF:

Microphthalmia-associated transcription factor

L-DOPA:

3,4-Dihydroxyphenylalanine

IBMX:

3-Isobutyl-1-methylxanthine

PTU:

N-phenylthiourea

MAPKs:

Mitogen-activated protein kinase

TEM:

Transmission electron microscope

HPLC:

High-performance liquid chromatography

Cdc42:

Cell division cycle protein 42

PMEL-17:

Pre-melanosome protein 17

Rab27a:

Ras-related protein Rab27a

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Acknowledgements

An appreciated thank to Dr. Yingchun Wu for identifying the plant.

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No funding was received to assist with the preparation of this manuscript.

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Authors and Affiliations

  1. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    **aoye Li, Lijia Chen, Hong Wang, Yiming Li, Huali Wu & Fujiang Guo

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  1. **aoye Li
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  2. Lijia Chen
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  3. Hong Wang
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  4. Yiming Li
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Contributions

**aoye Li: Conceptualization, Investigation, Data curation, Writing—original draft. Lijia Chen: Methodology. Hong Wang: Methodology. Yiming Li: Supervision. Huali Wu: Supervision, Review. Fujiang Guo: Supervision, Writing—review & editing.

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Correspondence to Huali Wu or Fujiang Guo.

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Li, X., Chen, L., Wang, H. et al. Germacrone, isolated from Curcuma wenyu**, inhibits melanin synthesis through the regulation of the MAPK signaling pathway. J Nat Med (2024). https://doi.org/10.1007/s11418-024-01818-x

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