Bee-derived antibacterial peptide, defensin-1, promotes wound re-epithelialisation in vitro and in vivo

Abstract

Royal jelly (RJ) has successfully been used as a remedy in wound healing. RJ has multiple effects, including antibacterial, anti-inflammatory and immunomodulatory activities, in various cell types. However, no component(s) (other than antibacterial) have been identified in RJ-accelerated wound healing. In this study, we demonstrate that keratinocytes are responsible for the elevated production of matrix metalloproteinase-9 (MMP-9) after incubation with a water extract of RJ. Furthermore, the keratinocyte migration and wound closure rates were significantly increased in the presence of RJ extract. MMP-9 production was reduced significantly following proteinase K treatment but remained stable after heat treatment, indicating that active component(s) have a proteinous character. To identify the component responsible for inducing MMP-9 production, RJ extract was fractionated using C18 RP-HPLC. In fractions exhibiting stimulatory activity, we immunochemically detected the bee-derived antibacterial peptide, defensin-1. Defensin-1 was cloned, and recombinant peptide was produced in a baculoviral expression system. Defensin-1 stimulated MMP-9 secretion from keratinocytes and increased keratinocyte migration and wound closure in vitro. In addition, defensin-1 promoted re-epithelisation and wound closure in uninfected excision wounds. These data indisputably demonstrate that defensin-1, a regular but concentration variable factor found in honey and RJ, contributes to cutaneous wound closure by enhancing keratinocyte migration and MMP-9 secretion.

New Insights into the Biological and Pharmaceutical Properties of Royal Jelly

“…A protein fraction, mainly containing MRJP-2,3,7 have the potential to influence wound healing bioactivity by stimulating keratinocyte growth and migration suggests that these proteins promote the development of new wound healing medication [130]. The defensin-1 peptide in RJ contributes to skin regeneration and cutaneous wound closure by increasing matrix metalloproteinase-9 secretion and keratinocyte migration [131].…”

Bee Products in Dermatology and Skin Care

“…Moreover defensin-1 promotes reepithelization and wound closure. Similarly as in honey, defensin-1 is responsible for cutaneous wound closure by enhancing keratinocyte and MMP-9 secretion [69]. Royal jelly is effective in the treatment of wounds, and is successfully used in cosmetics for problem skin care.…”

Royal jelly-derived proteins enhance proliferation and migration of human epidermal keratinocytes in an in vitro scratch wound model

“…Many studies have reported that royal jelly possesses a plethora of biological activities, including antimicrobial [6][7][8][9], anti-inflammatory [10], anti-tumour [11], antioxidant [12], immunomodulatory [13] and growthpromoting [14] effects. What is more, it has been documented to be used in folk medicine for the facilitation of wound healing since ancientry [15]. Although some studies have indicated that topical application of royal jelly can shorten the period of infected or uninfected wound healing in animal models and even diabetic foot ulcers [16][17][18], the substances and precise mechanisms associated with wound healing are still poorly investigated.…”

“…Although some studies have indicated that topical application of royal jelly can shorten the period of infected or uninfected wound healing in animal models and even diabetic foot ulcers [16][17][18], the substances and precise mechanisms associated with wound healing are still poorly investigated. Previous studies merely reported that royal jelly components, especially 10-hydroxy-2-decenoic acid (10-HDA) 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].…”