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. 2025;32(38):8664-8677.
doi: 10.2174/0109298673341645240919072455.

Phenolic Glycoside Monomer from Reed Rhizome Inhibits Melanin Production via PI3K-Akt and Ras-Raf-MEK-ERK Pathways

Meijun Pang  1   2   3 , Hong Yao  1   2   3 , Kechen Bao  1   2   3 , Ruitian Xu  1   2   3 , Rongjiao Xi  1   2   3 , Rui Peng  1   2   3 , Hui Zhi  1   2   3 , Kuo Zhang  1   2   3 , Runnan He  1   2   3 , Yunfei Du  4 , Yanfang Su  4 , Xiuyun Liu  1   2   3 , Dong Ming  1   2   3
Affiliations

Phenolic Glycoside Monomer from Reed Rhizome Inhibits Melanin Production via PI3K-Akt and Ras-Raf-MEK-ERK Pathways

Meijun Pang et al. Curr Med Chem. 2025.

Abstract

Introduction: Melanogenesis, the process responsible for melanin production, is a critical determinant of skin pigmentation. Dysregulation of this process can lead to hyperpigmentation disorders.

Methods: In this study, we identified a novel Reed Rhizome extract, (1'S, 2'S)-syringyl glycerol 3'-O-β-D-glucopyranoside (compound 5), and evaluated its anti-melanogenic potential in zebrafish models and in vitro assays. Compound 5 inhibited melanin synthesis by 36.66% ± 14.00% and tyrosinase in vivo by 48.26% ± 6.94%, surpassing the inhibitory effects of arbutin. Network pharmacological analysis revealed key targets, including HSP90AA1, HRAS, and PIK3R1, potentially involved in the anti-melanogenic effects of compound 5.

Results: Molecular docking studies supported the interactions between compound 5 and these targets. Further, gene expression analysis in zebrafish indicated that compound 5 up-regulates hsp90aa1.1, hrasa, and pik3r1, and subsequently down-regulating mitfa, tyr, and tyrp1, critical genes in melanogenesis.

Conclusion: These findings suggest that compound 5 inhibits melanin production via PI3K-Akt and Ras-Raf-MEK-ERK signaling pathways, positioning it as a promising candidate for the treatment of hyperpigmentation.

Keywords: Reed Rhizome extract; age spots; anti-melanogenesis; radicals.; tyrosinase; zebrafish model.

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Conflict of interest statement

The authors declare no conflict of interest, financial or otherwise.

Figures

Fig. (1)
Fig. (1)
Results of preliminary screening experiment. (A) Chemical structures of the seven natural products candidates. Compound 1 belongs to phenolic glycosides and compounds 2-7 belong to phenylpropanoid glycosides. (B) The anti-melanogenesis effect of compound 5 at 1500 μg/mL was better than that of arbutin at the same concentration.
Fig. (2)
Fig. (2)
(A-C) Compound 5 significantly inhibited melanogenesis and tyrosinase activity both in vivo and in potato in vitro ***p < 0.001, **p < 0.01 and *p < 0.05 as compared with the control group.
Fig. (3)
Fig. (3)
Compound 5 may act on HSP90AA1 or (and) HRAS or (and) PIK3R1 to inhibit melanogenesis. (A) The Venn diagram of compound 5 and melanin targets. (B) PPI of cross-targeted proteins, with the outermost circle of degree 1-3, the middle circle of 4-7, and the smallest circle of 8-11. (C) GO analysis of genes encoding proteins targeted by compound 5. (D) KEGG analysis of genes encoding proteins targeted by compound 5. (E-G) 2D and 3D docking diagrams between compound 5 and core target proteins. The boxes represented amino acid residues, the letter “A” or “B” preceding the amino acid abbreviation represented the A or B chain of the protein, and the number following it represented the serial number of the amino acid in the polypeptide chain.
Fig. (4)
Fig. (4)
(A-F) Compound 5 up-regulated the gene expression of hsp90aa1.1, hrasa and pik3r1, while down-regulating the gene expression of mitfa, tyr and tyrp1 in zebrafish larvae. ***p < 0.001, **p < 0.01 and *p < 0.05 as compared with the control group.
See this image and copyright information in PMC

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