Abstract

BackgroundSkin injury is inevitable in daily life. In recent years, with the increasing morbidity of diseases such as diabetes and metabolic disorders, chronic wounds have become a considerable challenge in clinical practice. Royal jelly, reported to have multifarious biological and physiological properties, has been used as a remedy for a variety of wounds since ancient times. However, the active components and mechanisms underlying the wound-healing properties of royal jelly are still largely unknown.MethodsWater-soluble proteins of royal jelly were fractionated and investigated for the proliferative and migratory effects on human epidermal keratinocytes (HaCaT) in an in vitro wound healing model. The proteins present in bioactive fractions were characterised and quantified using Label-free protein quantification method. The potential functions of these proteins in biological systems were further analysed using bioinformatic tools.ResultsA protein fraction, mainly containing major royal jelly proteins 2 (MRJP2), MRJP3 and MRJP7, stimulated proliferative and migratory activities in HaCaT cells without visible cytotoxicity. It exerted the greatest effects on the growth of HaCaT cells in the first 48 h. Furthermore, when treated with this protein fraction, the closure rates of the in vitro scratch wound were significantly increased. Functional analysis indicated that MRJP2, MRJP3 and MRJP7 were associated with carbohydrate transport and metabolism.ConclusionsWe fractionated the water-soluble proteins of royal jelly and identified one fraction (Fraction 2) that induced both proliferative and migratory effects on a human epidermal keratinocyte cell line. Major royal jelly proteins (MRJP2, MRJP3 and/or MRJP7) were speculated to possess potential wound-healing bioactivity. This is the first report that royal jelly may improve wound closure via MRJP-induced cellular proliferation and migration. These proteins may be valuable lead compounds for the development of novel wound healing medications. Our findings would facilitate better understanding of the wound repair mechanisms of royal jelly.

Highlights

  • Skin injury is inevitable in daily life

  • Previous studies merely reported that royal jelly components, especially 10-hydroxy-2-decenoic acid (10HDA) and defensin-1, might accelerate wound healing through anti-inflammation, promoting synthesis of growth factors, or migration of skin fibroblasts or keratinocytes [15, 19,20,21,22]; major royal jelly proteins (MRJPs) could induce proliferation of several human cell lines [23]

  • A water-soluble protein fraction mainly consisting of major royal jelly proteins 2 (MRJP2), MRJP3 and MRJP7 was found to induce proliferative and migratory effects in human epidermal keratinocytes (HaCaT) without obvious cytotoxicity, implying the potential of MRJPs in the healing of cutaneous wounds. This is the first report that royal jelly may improve wound closure via MRJP-induced cellular proliferation and migration

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Summary

Introduction

Skin injury is inevitable in daily life. In recent years, with the increasing morbidity of diseases such as diabetes and metabolic disorders, chronic wounds have become a considerable challenge in clinical practice. Food given exclusively to larvae and queen bees, is synthesised and secreted by the glands located in the hypopharynx and mandible of nurse honeybees It is composed of 60–70% water, 11–23% carbohydrate, 9– 18% protein, 4–8% lipid and 0.8–3% other compounds such as vitamins, salts, amino acids and minerals [1,2,3,4]. Previous studies merely reported that royal jelly components, especially 10-hydroxy-2-decenoic acid (10HDA) and defensin-1, might accelerate wound healing through anti-inflammation, promoting synthesis of growth factors, or migration of skin fibroblasts or keratinocytes [15, 19,20,21,22]; MRJPs could induce proliferation of several human cell lines [23]

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