# Determination via an Integration Strategy of the Potential Dermal ECM Reconstruction Mechanism by Which the WAW Formula Alleviates Skin Aging

**Authors:** Yingying Lin, Yunhee Chang, Yoojae Maeng, Xiaoxing Liu, Xinke Liu, Hong Meng, Fan Yi

PMC · DOI: 10.1111/jocd.70124 · 2025-03-31

## TL;DR

This study explores how a traditional Chinese medicine formula called WAW helps reduce skin aging by affecting the skin's structure and function.

## Contribution

The study introduces a new strategy for integrating TCM into cosmetics and reveals the mechanism by which WAW combats skin aging.

## Key findings

- The WAW formula inhibits NO production and tyrosinase activity while increasing mRNA expression of filaggrin, AQP, and HAS2.
- The formula upregulates TGF-β1 and downregulates MMP-2/MMP-9, supporting ECM maintenance and skin health.
- The study provides a framework for using TCM in modern skincare and identifies morroniside as an active ingredient.

## Abstract

Traditional Chinese medicine (TCM) treats skin conditions and delays aging using specific formulas. TCM links skin health to internal organ functions: kidney qi deficiency accelerates aging, whereas spleen deficiency leads to dry, loose skin from insufficient qi and blood. The renowned spleen‐tonifying and kidney‐nourishing formula “Wan An Wan” moisturizes the skin, but its antiageing mechanism remains unclear.

The aim of this study was to investigate the development strategy and comprehensive methodological framework for incorporating TCM into cosmetics and to assess the mechanism of action and application potential of the WAW formula in mitigating skin aging.

In vitro experiments revealed that after optimizing the extraction of the active ingredients of the tailored WAW formula, it effectively inhibited NO production and tyrosinase activity and increased filaggrin, AQP, and HAS2 mRNA expression. Moreover, the active ingredients, including morroniside, were also analyzed separately. Mechanistic studies revealed that the tailored WAW formula upregulated the expression of the TGF‐β1 gene associated with ECM production and downregulated the expression of the MMP‐2/MMP‐9 genes associated with ECM degradation, regulating cell behaviors such as migration, adhesion, and proliferation and thereby maintaining the healthy state of the skin.

In this study, an overall strategy for applying TCM for the development of skin care solutions was established, the potential value of WAW in modern dermatologic applications was revealed, innovative raw materials with comprehensive effects were developed, and new ideas for the fields of cosmetics and dermatology were provided.

## Linked entities

- **Genes:** LOC102285057 (hornerin) [NCBI Gene 102285057], AQP (aquaporin) [NCBI Gene 36456], HAS2 (hyaluronan synthase 2) [NCBI Gene 3037], TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040], MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313], MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318]
- **Chemicals:** morroniside (PubChem CID 11228693)

## Full-text entities

- **Genes:** HAS2 (hyaluronan synthase 2) [NCBI Gene 3037], TYR (tyrosinase) [NCBI Gene 7299] {aka ATN, CMM8, OCA1, OCA1A, OCAIA, SHEP3}, FLG (filaggrin) [NCBI Gene 2312] {aka ATOD2, FLG-1, FLG1}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}
- **Chemicals:** morroniside (MESH:C488401), NO (MESH:D009614)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11955934/full.md

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Source: https://tomesphere.com/paper/PMC11955934