Salidroside Selectively Binds to SEC23A and Ameliorates Psychological Stress-Induced Hyperpigmentation
Man Yang1, Xiaoyu Sun1, Da Wang1
1Department of TCM Chemistry, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Pharmaceuticals (Basel, Switzerland)
|March 28, 2026
Summary
Salidroside (SAL) effectively treats psychological stress-induced hyperpigmentation by targeting SEC23A. This natural compound inhibits melanin production through specific signaling pathways, offering a novel therapeutic approach for stress-related skin conditions.
Area of Science:
- Dermatology
- Pharmacology
- Molecular Biology
Background:
- Psychological stress exacerbates hyperpigmentation through neuroendocrine pathways.
- Targeted treatments for stress-induced hyperpigmentation are limited.
- Salidroside (SAL) shows depigmenting and neuroprotective effects.
Purpose of the Study:
- To investigate SAL's efficacy in treating psychological stress-induced hyperpigmentation.
- To elucidate the molecular mechanisms underlying SAL's action.
- To identify SAL's direct molecular target in stress-induced melanogenesis.
Main Methods:
- Utilized B16F10 melanocytes, mice, zebrafish, and human skin explants.
- Modeled stress-induced hyperpigmentation with Substance P/cortisol and canonical hyperpigmentation with α-MSH/IBMX.
- Employed DARTS, molecular docking, and siRNA to identify and validate SAL's target (SEC23A) and pathways.
Main Results:
- SAL reduced melanin, tyrosinase activity, and melanogenic gene expression in stress models.
- SAL reversed hyperpigmentation in vivo and in vitro, normalizing melanosomes.
- Identified SEC23A as a direct target, with SAL inhibiting its upregulation and modulating ERK/p38 MAPK pathways.
Conclusions:
- SEC23A is a novel key target for psychological stress-induced hyperpigmentation.
- SAL selectively inhibits stress-induced melanogenesis by binding SEC23A via ERK and p38 MAPK pathways.
- SAL's mechanism is distinct from canonical cAMP pathway inhibition, showing etiological specificity.
