Aspergillus oryzae-Fermented Wheat Peptone Enhances the Potential of Proliferation and Hydration of Human Keratinocytes through Activation of p44/42 MAPK.

Kyung Man Hahm,Sae Woong Oh,Seoyeon Yang,Ji Hye Kim,Hyun Sook Yeom,See-Hyoung Park,Jin Oh Park,Jae Youl Cho,Hye Ja Lee,Jongsung Lee

doi:10.3390/molecules26196074

Abstract

Identifying materials contributing to skin hydration, essential for normal skin homeostasis, has recently gained increased research interest. In this study, we investigated the potential benefits and mechanisms of action of Aspergillus oryzae-fermented wheat peptone (AFWP) on the proliferation and hydration of human skin keratinocytes, through in vitro experiments using HaCaT cell lines. The findings revealed that compared to unfermented wheat peptone, AFWP exhibited an improved amino acid composition, significantly (p < 0.05) higher DPPH scavenging capability and cell proliferation activity, and reduced lipopolysaccharide-induced NO production in RAW 264.7 cells. Furthermore, we separated AFWP into eleven fractions, each ≤2 kDa; of these, fraction 4 (AFW4) demonstrated the highest efficacy in the cell proliferation assay and was found to be the key component responsible for the cell proliferation potential and antioxidant properties of AFWP. Additionally, AFW4 increased the expression of genes encoding natural moisturizing factors, including filaggrin, transglutaminase-1, and hyaluronic acid synthase 1–3. Furthermore, AFW4 activated p44/42 MAPK, but not JNK and p38 MAPK, whereas PD98059, a p44/42 MAPK inhibitor, attenuated the beneficial effects of AFW4 on the skin, suggesting that the effects of AFW4 are mediated via p44/42 MAPK activation. Finally, in clinical studies, AFW4 treatment resulted in increased skin hydration and reduced trans-epidermal water loss compared with a placebo group. Collectively, these data provide evidence that AFW4 could be used as a potential therapeutic agent to improve skin barrier damage induced by external stresses.

Highlights

Aspergillus oryzae-fermented wheat peptone (AFWP) enhanced the proliferation potential of HaCaT cells, evidenced by BrdU cell proliferation assay (Figure 2A) and EdU staining assay (Figure 2B). These data indicate that the fermentation by A. oryzae contributed to the increased antioxidant and cell proliferation activities of wheat peptone
We demonstrated that AFW4 induced the In addition, the clinical studygenes showed that improved hydration and decreased upregulation of natural moisturizing factors (NMFs)-related such as AFW4
A previous study reported that vegetable peptones can induce cell proliferation and that ribosomal s6 kinase- CCAAT/enhancer binding protein β activation pathway [32]. In this the mechanisms underlying these actions may be mediated via the Raf- p44/42 MAPKstudy, we demonstrated that AFW4 significantly promotes cell proliferation potential, and p90 ribosomal s6 kinase- CCAAT/enhancer binding protein β activation pathway [32]

Summary

Introduction

Skin is the primary defense organ against a harmful external environment. Skin functions as a sensory receptor and regulator of body temperature and moisture content [1,2]. These additional functions of skin contribute to skin homeostasis. The disruption of skin homeostasis leads to skin aging, an emerging global health challenge expected to increase with increasing growth in the aged population. Mainly attributed to abnormal cellular physiology, results from extrinsic and intrinsic factors [3]

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Conclusion