# Enhancement of the Moisturizing Effect in an Injectable Sodium Hyaluronate Composite Solution by the Addition of Glycine, Alanine, and Proline

**Authors:** Anxin Shi, Yayun Guan, Shijie Chen, Yibing Ding, Yingrui Chen, Shuiyun Zeng, Yiqiao Hu, Hong Dong

PMC · DOI: 10.1111/jocd.70782 · 2026-03-06

## TL;DR

A new injectable solution combining hyaluronate with amino acids improves skin hydration and repair better than traditional treatments.

## Contribution

A novel injectable hyaluronate solution with glycine, alanine, and proline was developed and shown to enhance moisturizing effects.

## Key findings

- Co-ISHA significantly improved moisturizing efficacy compared to single-component hyaluronate.
- The formulation promoted production of moisturizing-related genes and natural moisturizing factors.
- Both cellular and tissue-level models confirmed enhanced protection and repair under dry conditions.

## Abstract

Hyaluronate (HA) is widely utilized in skin rejuvenation treatments, yet mono‐component injectable sodium hyaluronate solution (ISHA) is limited by its modest moisturizing performance and frequent dosing requirements. The combination of HA with active ingredients such as amino acids represent a promising strategy to improve hydration efficacy.

This study aimed to develop a novel injectable sodium hyaluronate composite solution (Co‐ISHA) incorporating three amino acids—glycine, alanine, and proline—and to systematically evaluate its moisturizing effects through phenomenological and mechanistic analyses at cellular and tissue levels.

This study developed a novel Co‐ISHA containing glycine, alanine, and proline, and evaluated its moisturizing performance through a comprehensive in vitro assessment system. The reparative and protective effects of Co‐HA on cells and tissues under dry conditions were examined, along with the expression of moisturizing‐related genes and natural moisturizing factors (NMF). This system integrated both cellular and tissue‐level models to elucidate the underlying mechanisms.

The results indicated that the addition of these three amino acids significantly enhanced the moisturizing efficacy of hyaluronic acid (HA). Both cellular and tissue‐level evidence confirmed that, compared to single‐component HA, Co‐ISHA more effectively protected and repaired cells damaged by dryness and promoted the production of moisturizing‐related genes and NMF.

This study successfully developed a Co‐ISHA formulation with superior moisturizing properties and established a robust in vitro evaluation system for assessing hydration efficacy. The findings provide a strategic framework for advancing the development of “Cruelty‐Free” cosmetic products.

## Linked entities

- **Chemicals:** glycine (PubChem CID 750), alanine (PubChem CID 239), proline (PubChem CID 614)

## Full-text entities

- **Genes:** COL1A1 (collagen type I alpha 1 chain) [NCBI Gene 1277] {aka CAFYD, EDSARTH1, EDSC, OI1, OI2, OI3}, CAT (catalase) [NCBI Gene 847], HAS3 (hyaluronan synthase 3) [NCBI Gene 3038], TJP1 (tight junction protein 1) [NCBI Gene 7082] {aka ZO-1}, Has3 (hyaluronan synthase 3) [NCBI Gene 15118], Has1 (hyaluronan synthase 1) [NCBI Gene 15116] {aka HAS}, Aqp3 (aquaporin 3) [NCBI Gene 11828] {aka AQP-2}, Col1a1 (collagen, type I, alpha 1) [NCBI Gene 12842] {aka Col1a-1, Cola-1, Cola1, Mov-13, Mov13}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, Has2 (hyaluronan synthase 2) [NCBI Gene 15117], FLG (filaggrin) [NCBI Gene 2312] {aka ATOD2, FLG-1, FLG1}, GSR (glutathione-disulfide reductase) [NCBI Gene 2936] {aka CNSHA10, GR, GSRD, HEL-75, HEL-S-122m}, HAS1 (hyaluronan synthase 1) [NCBI Gene 3036] {aka HAS}, Cd44 (CD44 antigen) [NCBI Gene 12505] {aka HERMES, Ly-24, Pgp-1}, HAS2 (hyaluronan synthase 2) [NCBI Gene 3037], Flg (filaggrin) [NCBI Gene 14246] {aka ft}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, AQP3 (aquaporin 3 (Gill blood group)) [NCBI Gene 360] {aka AQP-3, GIL}, Tjp1 (tight junction protein 1) [NCBI Gene 21872] {aka ZO1}
- **Diseases:** dry injury (MESH:D015352), ichthyosis (MESH:D007057), atopic dermatitis (MESH:D003876), Chemical Injury (MESH:D056486), laxity (MESH:D007593), Dryness (MESH:D014987), water loss (MESH:D000069578), SKIN (MESH:C564309), Sryness Injury (MESH:D014947), skin inflammation (MESH:D007249), NMF (MESH:D000077428)
- **Chemicals:** urea (MESH:D014508), amino acids (MESH:D000596), Glycerol (MESH:D005990), DCF (MESH:D015649), glycosaminoglycan (MESH:D006025), DCFH (-), ROS (MESH:D017382), trans-urocanic acid (MESH:D014560), DMSO (MESH:D004121), PBS (MESH:D007854), FBS (MESH:C523711), lipid (MESH:D008055), glutathione (MESH:D005978), CO2 (MESH:D002245), SYBR Green (MESH:C098022), Co (MESH:D003035), Alanine (MESH:D000409), acetonitrile (MESH:C032159), UCA (MESH:D014527), vitamin E (MESH:D014810), nitrogen (MESH:D009584), lactic acid (MESH:D019344), FITC (MESH:D016650), ammonium formate (MESH:C030544), sugars (MESH:D000073893), methanol (MESH:D000432), T (MESH:D014316), Proline (MESH:D011392), Glycine (MESH:D005998), HA (MESH:D006820), vitamin C (MESH:D001205), PCA (MESH:D011761), DCFH-DA (MESH:C029569), CCK-8 (MESH:D012844), water (MESH:D014867)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** C-25 C
- **Cell lines:** HaCaT — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0038)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12966627/full.md

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Source: https://tomesphere.com/paper/PMC12966627