Aloesin from Aloe vera accelerates skin wound healing by modulating MAPK/Rho and Smad signaling pathways in vitro and in vivo

Abstract

Background: Cutaneous wound healing is a complex process involving various regulatory factors at the molecular level. Aloe vera is widely used for cell rejuvenation, wound healing, and skin moisturizing. Hypothesis/Purpose: This study aimed to investigate the effects of aloesin from Aloe vera on cutaneous wound healing and mechanisms involved therein. Study Design: This study consisted of both in vitro and in vivo experiments involving skin cell lines and mouse model to demonstrate the wound healing effects of aloesin by taking into account several parameters ranging from cultured cell migration to wound healing in mice. Methods: The activities of Smad signaling molecules (Smad2 and Smad3), MAPKs (ERK and JNK), and migration-related proteins (Cdc42, Rac1, and a-Pak) were assessed after aloesin treatment in cultured cells (1, 5 and 10 mu M) and mouse skin (0.1% and 0.5%). We also monitored macrophage recruitment, secretion of cytokines and growth factors, tissue development, and angiogenesis after aloesin treatment using IHC analysis and ELISAs. Results: Aloesin increased cell migration via phosphorylation of Cdc42 and Rac1. Aloesin positively regulated the release of cytokines and growth factors (IL-1 beta, IL-6, TGF-beta 1 and TNF-alpha) from macrophages (RAW264.7) and enhanced angiogenesis in endothelial cells (HUVECs). Aloesin treatment accelerated wound closure rates in hairless mice by inducing angiogenesis, collagen deposition and granulation tissue formation. More importantly, aloesin treatment resulted in the activation of Smad and MAPK signaling proteins that are key players in cell migration, angiogenesis and tissue development. Conclusion: Aloesin ameliorates each phase of the wound healing process including inflammation, proliferation and remodeling through MAPK/Rho and Smad signaling pathways. These findings indicate that aloesin has the therapeutic potential for treating cutaneous wounds. (C) 2017 Elsevier GmbH. All rights reserved.