In Vitro and Clinical Dermatological Effects of Rubus crataegifolius Fruit Extracts on Human Fibroblasts and Keratinocytes

Background/Objectives: Rubus crataegifolius Bunge (Rosaceae, RC), a wild raspberry native to East Asia, has been investigated for the biological properties of its leaves and roots, while the dermatological potential of its fruit remains largely unexplored. This research evaluated the dermatological effects of RC fruit extracts, focusing on their potential for skin regeneration and anti-aging applications. Methods: RC fruit extracts were prepared by ultrasound-assisted extraction (UAE) and maceration extraction (ME) with distilled water or 70% ethanol as solvents. Phytochemical profiling was performed by liquid chromatography–electrospray ionization–time-of-flight mass spectrometry (LC-ESI-TOF-MS). Dermatological activities were evaluated using fibroblast and keratinocyte proliferation, collagen synthesis, wound healing, and gene expression assays. Safety was assessed by cytotoxicity and inflammation assays. Skin hydration was evaluated in a human application test. Results: Various phytochemicals, including flavonoids, phenolic acids, organic acids, and terpenoids, were putatively annotated by LC-ESI-TOF-MS in the RC fruit extracts. Ethanol extracts exhibited higher flavonoid content and antioxidant activity; however, dermatological activities were not correlated with antioxidant activity. UAE-derived extracts enhanced fibroblast proliferation. All extracts promoted collagen synthesis, with ME-EtOH showing the highest increase. In wound-healing assays, ME-DW extracts promoted fibroblast wound closure, while UAE-DW enhanced keratinocyte migration. In keratinocytes, UAE-DW specifically upregulated HAS1 and HAS2 mRNA expression. Clinically, UAE-DW extract produced a significant increase in skin hydration and moisture distribution in healthy volunteers. Conclusions: RC fruit extracts exhibit biological activities, including enhanced fibroblast proliferation, collagen synthesis, wound healing, and skin hydration.