alpha-Viniferin Improves Facial Hyperpigmentation via Accelerating Feedback Termination of cAMP/PKA-Signaled Phosphorylation Circuit in Facultative Melanogenesis
- Authors
- Yun, Cheong-Yong; Ko, Seon Mi; Choi, Yong Pyo; Kim, Beom Joon; Lee, Jungno; Kim, Jae Mun; Kim, Ju Yeon; Song, Jin Yong; Kim, Song-Hee; Hwang, Bang Yeon; Hong, Jin Tae; Han, Sang-Bae; Kim, Youngsoo
- Issue Date
- 2018
- Publisher
- IVYSPRING INT PUBL
- Keywords
- alpha-viniferin; Caragana sinica; PKA inactivation; feedback loop; melanogenesis
- Citation
- THERANOSTICS, v.8, no.7, pp 2031 - 2043
- Pages
- 13
- Journal Title
- THERANOSTICS
- Volume
- 8
- Number
- 7
- Start Page
- 2031
- End Page
- 2043
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/1445
- DOI
- 10.7150/thno.24385
- ISSN
- 1838-7640
- Abstract
- 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 alpha-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 alpha-viniferin inhibited melanin production in alpha-melanocyte-stimulating hormone (alpha-MSH)-, histamine- or cell-permeable cAMP-activated melanocyte cultures. Moreover, topical application with C. sinica containing alpha-viniferin, a standard in quality control, decreased melanin index on facial melasma and freckles in patients. As a molecular basis, alpha-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. alpha-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 alpha-viniferin in the treatment of melanocyte-specific hyperpigmented disorder. Finally, C. sinica containing alpha-viniferin was approved as an antimelanogenic agent with topical application in skin hyperpigmentation.
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