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Spirulina Peptides Suppress UVB-Induced Skin Hyperpigmentation via Integrated Modulation of Melanogenesis and

Qiying Zeng¹, Kaiye Yang², Hongtao Gu¹

¹School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.

Antioxidants (Basel, Switzerland)

|February 27, 2026

Abstract

Background:

Hyperpigmentation disorders lack effective therapies due to efficacy and safety limitations. Spirulina-derived peptides (SPs) show promises as anti-melanogenic agents, but their mechanisms remain unclear.

Methods:

SPs (<1 kDa, 3-6 amino acids) were isolated and assessed for tyrosinase inhibition, antioxidant, and anti-glycation activities. In vitro effects were tested in B16F10 cells; transcriptomic profiling used RNA sequencing. In vivo efficacy was evaluated in UVB-induced hyperpigmentation mouse models.

Results:

SPs exhibited mixed-type kinetic inhibition of tyrosinase along with strong antioxidant and anti-glycation activities. In vitro, SP suppressed melanin synthesis by directly inhibiting tyrosinase, downregulating the cAMP/PKA/CREB cascade, and activating the PI3K/Akt/GSK-3β pathway, resulting in reduced MITF and tyrosinase expression. Transcriptomic analysis revealed broad regulation of melanogenesis and inflammatory pathways. In vivo, topical SP treatment significantly reduced UVB-induced hyperpigmentation and skin inflammation, correlating with decreased CREB phosphorylation and tyrosinase expression.

Conclusions:

SP acts as a dual anti-melanogenic/anti-inflammatory agent through enzyme inhibition and signaling modulation, offering a novel therapeutic strategy for inflammation-associated hyperpigmentation.

Keywords:

melanin pigmentation signaling pathway spirulina peptides tyrosinase

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