Proangiogenic and Collagen-Promoting Effects of a 70% Ethanol Extract of Grateloupia angusta in Cutaneous Wound Models

Marine red algae have been reported to contain a variety of bioactive compounds that are effective in promoting wound-healing processes. In the present study, the wound-healing potential of Grateloupia angusta, which has been rarely explored, was examined using in vitro and in vivo models. A 70% ethanol extract of G. angusta (GAE) was prepared and profiled by liquid chromatography–mass spectrometry (LC-MS). Its effects on the wound-healing process were examined using three different types of cells that participate in this process, namely, Raw264.7, human umbilical vein endothelial cells (HUVECs), and human dermal fibroblasts (HDFs). Various assays including migration/scratch, tube formation, procollagen type I C-peptide production, and Western blotting were used to investigate the therapeutic potential of GAE. In vivo efficacy was tested in a mouse full-thickness skin incision wound model. In HUVECs, GAE increased viability, migration, tube formation, and vascular endothelial growth factor (VEGF) expression. Raw264.7 cells also showed increased VEGF production following GAE treatment. In HDFs, GAE did not affect proliferation and migration, but did increase collagen production. In mice, GAE accelerated wound closure from day 3 to day 5 and increased granulation/matrix with higher proliferating cell nuclear antigen (PCNA) and cluster of differentiation 31 (CD31) expression after a single topical application. In addition, keratin 14 (K14) expression was restored in GAE-treated wound tissues, suggesting improved epidermal re-epithelialization. Taken together, GAE promotes matrix production and pro-angiogenic activity in vitro and improves early wound repair in vivo, suggesting that G. angusta is a promising marine-derived candidate for wound-healing adjuvants. The results of the present study support further bioassay-guided fractionation and mechanistic validation in future studies.