Targeting TGF-β/VEGF/NF-κB inflammatory pathway using the Polyphenols of Echinacea purpurea (L.) Moench to enhance wound healing in a rat model

The present study explores the metabolic profiling and molecular wound-healing mechanisms of Echinacea purpurea (L.) Moench (EP) flowers aqueous (AE) and ethanol (EE) extracts in an excision wound-healing model. Metabolic profiling of the extracts was investigated using UHPLC-ESI-TOF-MS and molecular networking. Antioxidant activity was carried out using the DPPH (1, 1-diphenyl-2-picrylhydrazyl) radical scavenging method and FRAP (ferric reducing antioxidant power). Carboxy methylcellulose gels of 5 and 10% of both aqueous (AE) and ethanol (EE) extracts were prepared. The wounds were explored macroscopically, histologically, and immunohistochemically. The UHPLC-ESI-TOF-MS method enabled the identification of 3 organic acids, 14 phenolic acids, 3 phenylethanoid glycosides, and 11 flavonoids from EP extracts. EE had significant antioxidant activity compared to AE. The EP treated wounds healed faster. The EE succeeded in improving healing properties and controlling the inflammatory response by reducing IL-6 and increasing IL-10 expression and enhancing angiogenesis and remodeling via increased NF-κB, TGF-β, VEGF, CD31 expression and α-SMA and collagen deposition. It is worth mentioning that the EE groups also showed improvement in the histopathological examination in a dose-dependent manner. The effectiveness of EE in wound-healing may be attributed to its higher content of polyphenols which also made the antioxidant potential of the EE and its capacity to donate electrons higher than that of AE. This study scientifically enables the understanding of the molecular mechanisms Echinacea purpurea extract in wound healing via modulating skin inflammatory response and indicates the potential usefulness of EP ethanol extract for wound healing.