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Updated: Aug 15, 2025
Quantification of Hypopigmentation Activity In Vitro
Published on: March 6, 2019
7-desacetoxy-6,7-dehydrogedunin discovered by high-throughput screening system suppresses melanogenesis through
Sujin Park1, Eun Ju Choi2, Ji Young Kim1
1Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Background:
Hyperpigmented skin disorders such as melasma and lentigo are common photoaging diseases that cause cosmetic problems. The pigmentation is usually exacerbated by ultraviolet (UV) radiation, and various factors and pathways are involved in UV-mediated melanogenesis. Adenosine 5'-triphosphate (ATP), a well-known molecular unit of intracellular energy, is also regarded as a mediator of UV-mediated melanogenesis via the P2X7 purinergic receptor.
Objective:
To discover natural substances with an anti-melanogenic effect through inhibition of ATP-P2X7 axis by high-throughput screening (HTS).
Methods:
Among natural compounds provided by the Korea Chemical Bank, chemical compounds with a P2X7 inhibiting effect were screened through an HTS system. Then the selected compounds were verified for their anti-melanogenic effect after treating primary human epidermal melanocytes (PHEMs) with and without ATP. The expression of MITF, tyrosinase, and PMEL/gp100 was analyzed by Western blot, and melanin content was measured as 405 nm absorbance.
Results:
Among 962 natural compounds, 58 showed greater than 80% suppression of YO-PRO-1 fluorescence, representing P2X7 activity. Among them, considering cell viability, chemical stability, and availability, 7-desaxacetoxy-6,7-dehydrogedunin (7DG), a limonoid natural compound, was selected. The expression of MITF, tyrosinase, and PMEL/gp100; tyrosinase enzyme activity; and melanin content, which were increased by ATP treatment were abrogated by 7DG. Even when 7DG was treated in PHEMs without addition of ATP, tyrosinase expression and melanin content were significantly decreased. Hypopigmenting effect of 7DG was confirmed in ex vivo culture of human skins.
Conclusions:
7DG has an anti-melanogenic effect through ATP-P2X7 pathway inhibition and could be a potential skin whitening material.
Insights
A natural compound, 7-desaxacetoxy-6,7-dehydrogedunin (7DG), effectively reduces melanin production by inhibiting the ATP-P2X7 pathway. This discovery offers a promising new avenue for developing skin whitening agents to combat hyperpigmentation.
Area of Science:
- Dermatology and Skin Biology
- Molecular Biology
- Natural Product Chemistry
Background:
- Hyperpigmented skin disorders like melasma and lentigo are common, exacerbated by UV radiation.
- Ultraviolet (UV) radiation stimulates melanogenesis through various pathways.
- Adenosine 5'-triphosphate (ATP) acts as a mediator in UV-induced melanogenesis via the P2X7 purinergic receptor.
Purpose of the Study:
- To identify natural compounds that inhibit the ATP-P2X7 axis, thereby reducing melanogenesis.
- Utilize high-throughput screening (HTS) to discover novel anti-melanogenic agents.
Main Methods:
- Screened 962 natural compounds from the Korea Chemical Bank for P2X7 inhibitory activity using HTS.
- Verified anti-melanogenic effects of selected compounds on primary human epidermal melanocytes (PHEMs).
- Analyzed key melanogenesis markers (MITF, tyrosinase, PMEL/gp100) and melanin content.
Main Results:
- Identified 7-desaxacetoxy-6,7-dehydrogedunin (7DG), a limonoid, as a potent P2X7 inhibitor with good viability and stability.
- 7DG abrogated ATP-induced increases in MITF, tyrosinase, PMEL/gp100, and melanin content.
- 7DG demonstrated significant melanin reduction and tyrosinase expression inhibition even without ATP stimulation, confirmed ex vivo.
Conclusions:
- 7DG exhibits significant anti-melanogenic properties by inhibiting the ATP-P2X7 pathway.
- 7DG represents a potential novel ingredient for skin whitening and treating hyperpigmentation disorders.
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