# Effect of Protease‐Treated Royal Jelly Extract on Facial Wrinkles: A Placebo‐Controlled, Double‐Blind, Parallel‐Group Study

**Authors:** Shiho Ikegami, Takashi Ito, Hideto Okamoto, Chizuru Fujikura, Hayate Itatani, Masayuki Yagi, Akio Ohkuma, Nobuaki Okumura, Ayanori Yamaki, Norihiro Shigematsu, Kayo Kunimoto, Masatoshi Jinnin

PMC · DOI: 10.1111/jocd.70503 · Journal of Cosmetic Dermatology · 2025-10-24

## TL;DR

A cream containing protease-treated royal jelly improved facial wrinkles and skin hydration in a clinical trial with Japanese women.

## Contribution

This is the first clinical study demonstrating wrinkle-improving effects of protease-treated royal jelly.

## Key findings

- pRJ cream reduced wrinkle depth and improved skin hydration compared to placebo.
- pRJ cream increased dermal thickness and altered bacterial microbiome on cheeks.
- pRJ cream upregulated COL17A1, a stem cell marker, in ex vivo studies.

## Abstract

No clinical trials have reported on the wrinkle‐improving effects of cosmetics which activate stem cells in vitro.

To evaluate the anti‐wrinkle effects of protease‐treated royal jelly (pRJ)‐containing cream application to the skin.

Seventy healthy Japanese women concerned about skin aging were treated with pRJ‐containing cream or placebo for 12 weeks using the split‐face method in a placebo‐controlled, double‐blind, parallel‐group study.

The pRJ‐containing cream group showed an improvement in the maximum depth and average depth of the biggest wrinkle in the crow's feet wrinkle, along with increased water content of the stratum corneum and dermal thickness, compared to the placebo group. Significant decreases in the relative amount of bacterial microbiome of the cheeks were observed only in the pRJ‐containing cream group. In the ex vivo study, expression of COL17A1, epidermal stem cell function marker, was significantly up‐regulated with the use of the pRJ‐containing cream compared with the placebo cream.

This is the first study to demonstrate the wrinkle‐improving effects of pRJ. Our results suggest that pRJ not only controls stratum corneum water content, dermal thickness, and bacterial microbiome, but also affects stem cell competition and mesenchymal stem cell activation. pRJ can reduce or eliminate certain skin concerns of women by improving age‐related wrinkles.

## Linked entities

- **Genes:** COL17A1 (collagen type XVII alpha 1 chain) [NCBI Gene 1308]

## Full-text entities

- **Genes:** COL17A1 (collagen type XVII alpha 1 chain) [NCBI Gene 1308] {aka BA16H23.2, BP180, BPA-2, BPAG2, ERED, JEB4}
- **Chemicals:** Protease-Treated Royal Jelly Extract (-), royal jelly (MESH:C058787), water (MESH:D014867)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12551441/full.md

## References

25 references — full list in the complete paper: https://tomesphere.com/paper/PMC12551441/full.md

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Source: https://tomesphere.com/paper/PMC12551441