Theranostics 2018; 8(7):2031-2043. doi:10.7150/thno.24385

Research Paper

α-Viniferin Improves Facial Hyperpigmentation via Accelerating Feedback Termination of cAMP/PKA-Signaled Phosphorylation Circuit in Facultative Melanogenesis

Cheong-Yong Yun1, Seon Mi Ko1, Yong Pyo Choi1, Beom Joon Kim2, Jungno Lee3, Jae Mun Kim3, Ju Yeon Kim4, Jin Yong Song1, Song-Hee Kim1, Bang Yeon Hwang1, Jin Tae Hong1, Sang-Bae Han1, Youngsoo Kim1✉

1. College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea.
2. Department of Dermatology, Chung-Ang University Hospital, Seoul 06973, Korea.
3. Bio-convergence R&D center, Coseedbiopharm Corporation, Cheongju 28161, Korea.
4. R&D Division, Celltrion Inc., Incheon 22014, Korea


Rationale: cAMP up-regulates microphthalmia-associated transcription factor subtype M (MITF-M) and tyrosinase (Tyro) in the generation of heavily pigmented melanosomes. Here, we communicate a therapeutic mechanism of hyperpigmented disorder by α-viniferin, an active constituent of Caragana sinica.

Methods: We used cAMP-elevated melanocyte cultures or facial hyperpigmented patches for pigmentation assays, and applied immunoprecipitation, immunobloting, RT-PCR or reporter gene for elucidation of the antimelanogenic mechanism.

Results: C. sinica or α-viniferin inhibited melanin production in α-melanocyte-stimulating hormone (α-MSH)-, histamine- or cell-permeable cAMP-activated melanocyte cultures. Moreover, topical application with C. sinica containing α-viniferin, a standard in quality control, decreased melanin index on facial melasma and freckles in patients. As a molecular basis, α-viniferin accelerated protein kinase A (PKA) inactivation via the reassociation between catalytic and regulatory subunits in cAMP-elevated melanocytes, a feedback loop in the melanogenic process. α-Viniferin resultantly inhibited cAMP/PKA-signaled phosphorylation of cAMP-responsive element-binding protein (CREB) coupled with dephosphorylation of cAMP-regulated transcriptional co-activator 1 (CRTC1), thus down-regulating expression of MITF-M or Tyro gene with decreased melanin pigmentation.

Conclusion: This study assigned PKA inactivation, a feedback termination in cAMP-induced facultative melanogenesis, as a putative target of α-viniferin in the treatment of melanocyte-specific hyperpigmented disorder. Finally, C. sinica containing α-viniferin was approved as an antimelanogenic agent with topical application in skin hyperpigmentation.

Keywords: α-viniferin, Caragana sinica, PKA inactivation, feedback loop, melanogenesis

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How to cite this article:
Yun CY, Mi Ko S, Pyo Choi Y, Kim BJ, Lee J, Mun Kim J, Kim JY, Song JY, Kim SH, Hwang BY, Tae Hong J, Han SB, Kim Y. α-Viniferin Improves Facial Hyperpigmentation via Accelerating Feedback Termination of cAMP/PKA-Signaled Phosphorylation Circuit in Facultative Melanogenesis. Theranostics 2018; 8(7):2031-2043. doi:10.7150/thno.24385. Available from