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Article

Calycosin, a Common Dietary Isoflavonoid, Suppresses Melanogenesis through the Downregulation of PKA/CREB and p38 MAPK Signaling Pathways

by
Kun-Chang Wu
1,†,
You-Cheng Hseu
2,†,
Yu-Ching Shih
2,
Govindan Sivakumar
3,
Jyun-Ting Syu
2,
Guan-Lin Chen
2,
Meng-Tien Lu
2 and
Po-Chen Chu
2,3,*
1
School of Pharmacy, College of Pharmacy, China Medical University, Taichung 406040, Taiwan
2
Department of Cosmeceutics and Graduate Institute of Cosmeceutics, China Medical University, Taichung 406040, Taiwan
3
Drug Development Center, China Medical University, Taichung 406040, Taiwan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2022, 23(3), 1358; https://doi.org/10.3390/ijms23031358
Submission received: 30 December 2021 / Revised: 23 January 2022 / Accepted: 24 January 2022 / Published: 25 January 2022
(This article belongs to the Section Biochemistry)
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Abstract

Calycosin, a bioactive isoflavonoid isolated from root extracts of Astragalus membranaceus, has been reported to inhibit melanogenesis, the mechanism of which remains undefined. In this study, we interrogated the mechanistic basis by which calycosin inhibits melanin production in two model systems, i.e., B16F10 melanoma cells and zebrafish embryos. Calycosin was effective in protecting B16F10 cells from α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis and tyrosinase activity. This anti-melanogenic effect was accompanied by decreased expression levels of microphthalmia-associated transcription factor (MITF), a key protein controlling melanin synthesis, and its target genes tyrosinase and tyrosinase-related protein-2 (TRP-2) in calycosin-treated cells. Mechanistically, we obtained the first evidence that calycosin-mediated MITF downregulation was attributable to its ability to block signaling pathways mediated by cAMP response element-binding protein (CREB) and p38 MAP kinase. The protein kinase A (PKA) inhibitor H-89 and p38 inhibitor SB203580 validated the premise that calycosin inhibits melanin synthesis and tyrosinase activity by regulating the PKA/CREB and p38 MAPK signaling pathways. Moreover, the in vivo anti-melanogenic efficacy of calycosin was manifested by its ability to suppress body pigmentation and tyrosinase activity in zebrafish embryos. Together, these data suggested the translational potential of calycosin to be developed as skin-lightening cosmeceuticals.
Keywords: calycosin; melanin; tyrosinase; MITF; TRP-2; PKA/CREB; p38 MAPK calycosin; melanin; tyrosinase; MITF; TRP-2; PKA/CREB; p38 MAPK
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MDPI and ACS Style

Wu, K.-C.; Hseu, Y.-C.; Shih, Y.-C.; Sivakumar, G.; Syu, J.-T.; Chen, G.-L.; Lu, M.-T.; Chu, P.-C. Calycosin, a Common Dietary Isoflavonoid, Suppresses Melanogenesis through the Downregulation of PKA/CREB and p38 MAPK Signaling Pathways. Int. J. Mol. Sci. 2022, 23, 1358. https://doi.org/10.3390/ijms23031358

AMA Style

Wu K-C, Hseu Y-C, Shih Y-C, Sivakumar G, Syu J-T, Chen G-L, Lu M-T, Chu P-C. Calycosin, a Common Dietary Isoflavonoid, Suppresses Melanogenesis through the Downregulation of PKA/CREB and p38 MAPK Signaling Pathways. International Journal of Molecular Sciences. 2022; 23(3):1358. https://doi.org/10.3390/ijms23031358

Chicago/Turabian Style

Wu, Kun-Chang, You-Cheng Hseu, Yu-Ching Shih, Govindan Sivakumar, Jyun-Ting Syu, Guan-Lin Chen, Meng-Tien Lu, and Po-Chen Chu. 2022. "Calycosin, a Common Dietary Isoflavonoid, Suppresses Melanogenesis through the Downregulation of PKA/CREB and p38 MAPK Signaling Pathways" International Journal of Molecular Sciences 23, no. 3: 1358. https://doi.org/10.3390/ijms23031358

APA Style

Wu, K.-C., Hseu, Y.-C., Shih, Y.-C., Sivakumar, G., Syu, J.-T., Chen, G.-L., Lu, M.-T., & Chu, P.-C. (2022). Calycosin, a Common Dietary Isoflavonoid, Suppresses Melanogenesis through the Downregulation of PKA/CREB and p38 MAPK Signaling Pathways. International Journal of Molecular Sciences, 23(3), 1358. https://doi.org/10.3390/ijms23031358

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