Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Phenolic acids in Panax ginseng inhibit melanin production through bidirectional regulation of melanin synthase transcription via different signaling pathways

  • Jianzeng Liu (Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine) ;
  • Xiaohao Xu (Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine) ;
  • Jingyuan Zhou (Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine) ;
  • Guang Sun (Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine) ;
  • Zhenzhuo Li (Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine) ;
  • Lu Zhai (Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine) ;
  • Jing Wang (Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine) ;
  • Rui Ma (Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine) ;
  • Daqing Zhao (Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine) ;
  • Rui Jiang (Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine) ;
  • Liwei Sun (Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine)
  • Received : 2022.11.15
  • Accepted : 2023.05.19
  • Published : 2023.11.01
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Abstract

Background: Our previous investigation indicated that the preparation of Panax ginseng Meyer (P. ginseng) inhibited melanogenesis. It comprised salicylic acid (SA), protocatechuic acid (PA), p-coumaric acid (p-CA), vanillic acid (VA), and caffeic acid (CA). In this investigation, the regulatory effects of P. ginseng phenolic acid monomers on melanin production were assessed. Methods: In vitro and in vivo impact of phenolic acid monomers were assessed. Results: SA, PA, p-CA and VA inhibited tyrosinase (TYR) to reduce melanin production, whereas CA had the opposite effects. SA, PA, p-CA and VA significantly downregulated the melanocortin 1 receptor (MC1R), cycle AMP (cAMP), protein kinase A (PKA), cycle AMP-response element-binding protein (CREB), microphthalmia-associated transcription factor (MITF) pathway, reducing mRNA and protein levels of TYR, tyrosinase-related protein 1 (TYRP1), and TYRP2. Moreover, CA treatment enhanced the cAMP, PKA, and CREB pathways to promote MITF mRNA level and phosphorylation. It also alleviated MITF protein level in α-MSH-stimulated B16F10 cells, comparable to untreated B16F10, increasing the expression of phosphorylation glycogen synthase kinase 3β (p-GSK3β), β-catenin, p-ERK/ERK, and p-p38/p38. Furthermore, the GSK3β inhibitor promoted p-GSK3β and p-MITF expression, as observed in CA-treated cells. Moreover, p38 and ERK inhibitors inhibited CA-stimulated p-p38/p38, p-ERK/ERK, and p-MITF increase, which had negative binding energies with MC1R, as depicted by molecular docking. Conclusion: P. ginseng roots' phenolic acid monomers can safely inhibit melanin production by bidirectionally regulating melanin synthase transcription. Furthermore, they reduced MITF expression via MC1R/cAMP/PKA signaling pathway and enhanced MITF post-translational modification via Wnt/mitogen-activated protein kinase signaling pathway.

Keywords

Acknowledgement

This work was supported by the National Natural Science Foundation of China [grant numbers U19A2013 and U20A20402] and the Science and Technology Development Plan of Jilin Province [grant numbers 20210304002YY].

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