# Margarita (Pearl) Extract Alleviates Melasma by Targeting CAMP‐Responsive Element Binding Protein 1

**Authors:** Liling Shen, Jia Yao

PMC · DOI: 10.1111/jocd.70087 · Journal of Cosmetic Dermatology · 2025-05-14

## TL;DR

Pearl extract may help treat melasma by targeting a specific protein and affecting genes related to skin pigmentation.

## Contribution

The study identifies CREB1 as a novel target for pearl in treating melasma.

## Key findings

- Pearl significantly improved melasma severity scores in patients.
- TYR and DCT are melasma-related genes affected by pearl through CREB1.
- Pearl inhibits melanoma cell activity and tyrosinase via CREB1/MITF.

## Abstract

Margarita (pearl) has detoxifying and skin barrier‐repairing properties. The study was to evaluate the therapeutic effect of pearl on melasma and to preliminarily explore its possible mechanism of action.

The efficacy of pearl on patients with melasma was evaluated by the melasma area and severity index (MASI) and physician's global assessment (PGA) score. DNA sequencing was performed on pharyngeal swab samples from patients with melasma to obtain gene loci related to melasma. The active compounds and potential targets for pearl were retrieved from Integrated Traditional Chinese Medicine and HERB databases. The relevant genes of melasma were obtained from the GeneCards database and intersected with the targets of pearl to identify potential targets of pearl against melasma. The potential targets were mapped for the KEGG pathway in the KEGG Mapper and verified using human melanoma A375 cells that were exposed to ultraviolet irradiation.

Pearl significantly improved the MASI and PGA scores of patients with melasma. DNA sequencing revealed that TYR and DCT were genes related to melasma. Calcium carbonate, iron, magnesium, manganese, silicon, strontium, and zinc were active compounds for pearl. CAMP‐responsive element binding protein 1 (CREB1) was the target of pearl against melasma. Pearl regulated microphthalmia‐associated transcription factors through CREB and affected melasma‐related genes TYR and DCT, which in turn inhibit melanoma cell activity and intracellular tyrosinase activity.

Pearl can alleviate melasma by targeting the CREB1/MITF axis and then the melasma‐related gene loci TYR and DCT.

## Linked entities

- **Genes:** TYR (tyrosinase) [NCBI Gene 7299], DCT (dopachrome tautomerase) [NCBI Gene 1638], CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385]
- **Chemicals:** calcium carbonate (PubChem CID 10112), iron (PubChem CID 23925), magnesium (PubChem CID 5462224), manganese (PubChem CID 23930), silicon (PubChem CID 5461123), strontium (PubChem CID 5359327), zinc (PubChem CID 23994)

## Full-text entities

- **Genes:** CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385] {aka CREB, CREB-1}, MITF (melanocyte inducing transcription factor) [NCBI Gene 4286] {aka CMM8, COMMAD, MI, MITF-A, WS2, WS2A}, DCT (dopachrome tautomerase) [NCBI Gene 1638] {aka OCA8, TRP-2, TYRP2}, TYR (tyrosinase) [NCBI Gene 7299] {aka ATN, CMM8, OCA1, OCA1A, OCAIA, SHEP3}
- **Diseases:** Melasma (MESH:D008548), skin pigmentation disorder (MESH:D010859), mental abnormalities (MESH:D008607), skin disease (MESH:D012871), organ dysfunction (MESH:D009102), melanoma (MESH:D008545), microphthalmia (MESH:D008850), inflammatory (MESH:D007249), hyperpigmentation (MESH:D017495), toxicity (MESH:D064420)
- **Chemicals:** Melanin (MESH:D008543), CCK8 (MESH:D012844), strontium (MESH:D013324), DMSO (MESH:D004121), L-DOPA (MESH:D007980), PBS (MESH:D007854), tyrosine (MESH:D014443), NaOH (MESH:D012972), Iron (MESH:D007501), sodium phosphate (MESH:C018279), Silica (MESH:D012822), Triton X-100 (MESH:D017830), silicon (MESH:D012825), aminoglycoside (MESH:D000617), zinc oxide (MESH:D015034), hydroquinone (MESH:C031927), forskolin (MESH:D005576), manganese (MESH:D008345), Magnesium (MESH:D008274), vinylidene difluoride (MESH:C007384), DMEM medium (-), CO2 (MESH:D002245), lactic acid (MESH:D019344), zinc (MESH:D015032), Calcium carbonate (MESH:D002119), metal (MESH:D008670), SDS (MESH:D012967)
- **Species:** Bletilla striata (species) [taxon 78707], Rosa canina (dog briar, species) [taxon 74635], Homo sapiens (human, species) [taxon 9606], Sinohyriopsis cumingii (species) [taxon 165450], Centella asiatica (Asiatic pennywort, species) [taxon 48106], Rhus chinensis (species) [taxon 289753]
- **Cell lines:** CCK8 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_2873), A375 — Homo sapiens (Human), Amelanotic melanoma, Cancer cell line (CVCL_0132)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12079008/full.md

## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12079008/full.md

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Source: https://tomesphere.com/paper/PMC12079008