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

**Authors:** Qiying Zeng, Kaiye Yang, Hongtao Gu, Changzhi Dong, Wei Zhou, Zhiyun Du

PMC · DOI: 10.3390/antiox15020181 · Antioxidants · 2026-01-30

## TL;DR

This study shows that Spirulina peptides can reduce skin darkening caused by UV light by targeting both pigment production and inflammation.

## Contribution

The study reveals the novel dual mechanism of Spirulina peptides in suppressing melanogenesis and inflammation pathways.

## Key findings

- Spirulina peptides inhibit tyrosinase and downregulate melanogenesis pathways in vitro.
- Transcriptomic analysis shows broad regulation of melanogenesis and inflammatory genes.
- Topical application of Spirulina peptides reduces UVB-induced hyperpigmentation and inflammation in mice.

## 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.

## Linked entities

- **Genes:** MITF (melanocyte inducing transcription factor) [NCBI Gene 4286], CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385], CAMP (cathelicidin antimicrobial peptide) [NCBI Gene 820], PKA (cAMP dependent protein kinase) [NCBI Gene 7451422], PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207], GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], LOC103429692 (polyphenol oxidase, chloroplastic-like) [NCBI Gene 103429692]
- **Chemicals:** UVB (PubChem CID 154464873)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Tyr (tyrosinase) [NCBI Gene 22173] {aka Oca1, albino, c, skc35}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 12912] {aka 2310001E10Rik, 3526402H21Rik, Creb, Creb-1}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, sps (spontaneous seizure) [NCBI Gene 20767] {aka dd}, Tyrp1 (tyrosinase-related protein 1) [NCBI Gene 22178] {aka Oca3, TRP-1, TRP1, Tyrp, b, brown}, Foxo3 (forkhead box O3) [NCBI Gene 56484] {aka 1110048B16Rik, 2010203A17Rik, FKHRL1, Fkhr2, Foxo3a}, Camp (cathelicidin antimicrobial peptide) [NCBI Gene 12796] {aka CAP18, CLP, Cnlp, Cramp, FALL39, MCLP}, Creb3 (cAMP responsive element binding protein 3) [NCBI Gene 12913] {aka LZIP, LZIP-1, LZIP-2, Luman}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Trp2 (tRNA proline 2) [NCBI Gene 104042] {aka Trp-2}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Il33 (interleukin 33) [NCBI Gene 77125] {aka 9230117N10Rik, Il-33, Il1f11, NF-HEV}, Csf2 (colony stimulating factor 2 (granulocyte-macrophage)) [NCBI Gene 12981] {aka CSF, Csfgm, GMCSF, Gm-CSf, MGI-IGM}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], Mitf (melanogenesis associated transcription factor) [NCBI Gene 17342] {aka BCC2, Bhlhe32, Gsfbcc2, Vitiligo, Wh, bw}, Il18 (interleukin 18) [NCBI Gene 16173] {aka Igif, Il-18}, Gsk3b (glycogen synthase kinase 3 beta) [NCBI Gene 56637] {aka 7330414F15Rik, 8430431H08Rik, GSK-3, GSK-3beta, GSK3}, Mc1r (melanocortin 1 receptor) [NCBI Gene 17199] {aka Mcr1, Mshra, Tob, e}, tyrosinase [NCBI Gene 100707700], Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Spl (plasma serotonin level) [NCBI Gene 104153], Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, Tff2 (trefoil factor 2 (spasmolytic protein 1)) [NCBI Gene 21785] {aka SP, mSP}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Blnk (B cell linker) [NCBI Gene 17060] {aka BASH, Bca, Ly-57, Ly57, Lyw-57, SLP-65}, Mapk3 (mitogen-activated protein kinase 3) [NCBI Gene 26417] {aka Erk-1, Erk1, Ert2, Esrk1, Mnk1, Mtap2k}, Dct (dopachrome tautomerase) [NCBI Gene 13190] {aka DT, TRP-2, TRP2, Tyrp-2, Tyrp2, slaty}
- **Diseases:** AGEs (MESH:D003643), melasma (MESH:D008548), carcinogenic (MESH:D011230), solar lentigines (MESH:D007911), cytotoxic (MESH:D064420), acanthosis (MESH:D000052), Hyperpigmentation (MESH:D017495), mitochondrial DNA damage (MESH:D028361), melanoma (MESH:D008545), injury to (MESH:D014947), abscess (MESH:D000038), Inflammation (MESH:D007249), hyperkeratosis (MESH:D017488), pigmentation (MESH:D010859)
- **Chemicals:** Melanin (MESH:D008543), lipid (MESH:D008055), Cys- (MESH:D003545), PFA (MESH:C003043), Diammonium 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (MESH:C002502), glutathione (MESH:D005978), CO2 (MESH:D002245), L-glutamine (MESH:D005973), AMP (MESH:D000249), polyphenol (MESH:D059808), MGO (MESH:D011765), ROS (MESH:D017382), glucose (MESH:D005947), DMSO (MESH:D004121), PVDF (MESH:C024865), DAB (MESH:C000469), sodium acetate (MESH:D019346), dopachrome (MESH:C001123), KCl (MESH:D011189), PBS (MESH:D007854), penicillin (MESH:D010406), sodium phosphate (MESH:C018279), polyunsaturated fatty acids (MESH:D005231), curcumin (MESH:D003474), S (MESH:D013455), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MESH:C022616), H&amp;E (MESH:D006371), 6 amino acids (-), hydrogen peroxide (MESH:D006861), potassium persulfate (MESH:C009007), eumelanin (MESH:C041877), AEBSF (MESH:C002010), Phe (MESH:D010649), Amino Acid (MESH:D000596), MTT (MESH:C070243), Trizol (MESH:C411644), PGE-2 (MESH:D015232), peptides (MESH:D010455), carotenoids (MESH:D002338), sodium azide (MESH:D019810), Leu (MESH:D007930), phenol (MESH:D019800), Water (MESH:D014867), Tyr (MESH:D014443), AGE (MESH:D017127), NaOH (MESH:D012972), E64 (MESH:C024974), Ethanol (MESH:D000431), Copper (MESH:D003300), SDS (MESH:D012967), ACN (MESH:C084683), HCl (MESH:D006851), essential amino acids (MESH:D000601), resveratrol (MESH:D000077185), oxygen (MESH:D010100), formazan (MESH:D005562), FA (MESH:C030544), kojic acid (MESH:C011890), NaCl (MESH:D012965), metal (MESH:D008670)
- **Species:** Oryza sativa (Asian cultivated rice, species) [taxon 4530], Bacillus sp. SA (species) [taxon 1168094], Tilapia (genus) [taxon 8126], Oreochromis niloticus (Nile tilapia, species) [taxon 8128], Homo sapiens (human, species) [taxon 9606], Spirulina (suborder) [taxon 551299], Agaricus bisporus (common mushroom, species) [taxon 5341], Limnospira platensis (species) [taxon 118562], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** SP — Homo sapiens (Human), Transformed cell line (CVCL_1Y11), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), /6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985), B16F10 — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0159)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12937610/full.md

## References

91 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937610/full.md

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Source: https://tomesphere.com/paper/PMC12937610