Royal jelly from different floral sources possesses distinct wound-healing mechanisms and ingredient profiles.

In recent years, population aging together with the increased prevalence of diabetes and obesity has fuelled a surge in the instances of cutaneous non-healing wounds. Royal jelly (RJ) is a traditional remedy for wound repair; however, the subjacent mechanisms and ingredient profiles are still largely unknown. Our previous study found that Castanea mollissima Bl. RJ (CmRJ-Zj) possessed superior wound healing-promoting effects on both the in vivo and in vitro models than Brassica napus L. RJ (BnRJ-Zj). This study conducted an in-depth investigation on the wound-repairing mechanisms of CmRJ-Zj and BnRJ-Zj to explain the previously observed phenomenon and also comprehensively characterized their constituents. It was found that chestnut RJ could enhance cutaneous wound healing by boosting the growth and mobility of keratinocytes, modulating the expression of aquaporin 3 (AQP3), regulating MAPK and calcium pathways, and mediating inflammatory responses. By employing LC-MS/MS-based proteomic and metabolomic techniques, the comprehensive molecules present in CmRJ-Zj and BnRJ-Zj were elucidated, resulting in a clear discrimination from each other. A total of 15 and 631 differential proteins and compounds were identified, and 217 proteins were newly found in RJ proteome. With bioinformatic functional analysis, we speculated that some differential components were responsible for the wound-healing properties of CmRJ-Zj. Therefore, this study provides an insight into the wound-healing mechanisms of RJ and is the first to explore the compositions of RJ from different nectar plants. It will facilitate the development of therapeutic agents from RJ to treat difficult-to-heal wounds and the distinction of different RJ categories.