Molecular mechanisms underlying Tao-Hong-Si-Wu decoction treating hyperpigmentation based on network pharmacology, Mendelian randomization analysis, and experimental verification

Abstract

Context

Hyperpigmentation, a common skin condition marked by excessive melanin production, currently has limited effective treatment options.

Objective

This study explores the effects of Tao-Hong-Si-Wu decoction (THSWD) on hyperpigmentation and to elucidate the underlying mechanisms.

Materials and methods

We employed network pharmacology, Mendelian randomization, and molecular docking to identify THSWD’s hub targets and mechanisms against hyperpigmentation. The Cell Counting Kit-8 (CCK-8) assay determined suitable THSWD treatment concentrations for PIG1 cells. These cells were exposed to graded concentrations of THSWD-containing serum (2.5%, 5%, 10%, 15%, 20%, 30%, 40%, and 50%) and treated with α-MSH (100 nM) to induce an in vitro hyperpigmentation model. Assessments included melanin content, tyrosinase activity, and Western blotting.

Results

ALB, IL6, and MAPK3 emerged as primary targets, while quercetin, apigenin, and luteolin were the core active ingredients. The CCK-8 assay indicated that concentrations between 2.5% and 20% were suitable for PIG1 cells, with a 50% cytotoxicity concentration (CC₅₀) of 32.14%. THSWD treatment significantly reduced melanin content and tyrosinase activity in α-MSH-induced PIG1 cells, along with downregulating MC1R and MITF expression. THSWD increased ALB and p-MAPK3/MAPK3 levels and decreased IL6 expression in the model cells.

Discussion and conclusion

THSWD mitigates hyperpigmentation by targeting ALB, IL6, and MAPK3. This study paves the way for clinical applications of THSWD as a novel treatment for hyperpigmentation and offers new targeted therapeutic strategies.

Keywords:

• Tyrosinase
• melanogenesis
• inflammatory response

Author’s contributions

The authors confirm contribution to the paper as follows: Conceptualization: JC; Data curation, Formal analysis, Investigation and Methodology: JC and WY; Project administration, Resources and Supervision: WY; Software: JC; Validation: WY; Visualization and Writing-original draft: JC; Writing-review & editing: WY. All authors reviewed the results and approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, [WY], upon reasonable request.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.