Euodia daniellii Hemsl. Extract and Its Active Component Hesperidin Accelerate Cutaneous Wound Healing via Activation of Wnt/β-Catenin Signaling Pathway

Abstract

The activation of the Wnt/β-catenin signaling pathway plays a key role in the wound-healing process through tissue regeneration. The extract of Euodia daniellii Hemsl. (E. daniellii), a member of the Rutaceae family, activates the Wnt/β-catenin signaling pathway. However, the function of E. daniellii in wound healing has not yet been elucidated. We performed a migration assay to determine the wound-healing effect of E. daniellii extract in vitro using human keratinocytes and dermal fibroblast. In addition, a mouse acute wound model was used to investigate the cutaneous wound-healing effect of E. daniellii extract in vivo and confirm the potential mechanism. E. daniellii extract enhanced the migration of human keratinocytes and dermal fibroblasts via the activation of the Wnt/β-catenin pathway. Moreover, the E. daniellii extract increased the levels of keratin 14, PCNA, collagen I, and α-SMA, with nuclei accumulation of β-catenin in vitro. E. daniellii extract also efficiently accelerated re-epithelialization and stimulated wound healing in vivo. Furthermore, we confirmed that hesperidin, one of the components of E. daniellii, efficiently accelerated the migration of human keratinocytes and dermal fibroblasts, as well as wound healing in vivo via the activation of the Wnt/β-catenin pathway. Overall, E. daniellii extract and its active component, hesperidin, have potential to be used as therapeutic agents for wound healing.

Hesperidin - loaded PVA/alginate hydrogel: targeting NFκB/iNOS/COX-2/TNF-α inflammatory signaling pathway

“…In vitro anti-inflammatory studies showed that PVA/AH hydrogel inhibited heat-induced HRBC hemolysis, hypotonicityinduced hemolysis, and egg albumin denaturation better than PVA/ A. The results indicate that H may play a significant antiinflammatory role (51,52) in membrane stabilization of HRBC.…”

“…In vitro anti-inflammatory studies showed that PVA/AH hydrogel inhibited heat-induced HRBC hemolysis, hypotonicity-induced hemolysis, and egg albumin denaturation better than PVA/A. The results indicate that H may play a significant anti-inflammatory role ( 51 , 52 ) in membrane stabilization of HRBC. In addition, since lysosomal membrane and HRBC membrane have the same components, thus H may have a significant role in the integrity of cell membrane damage ( 53 , 54 ), and inhibit lysosomal lysis during inflammation and the release of enzymes ( 55 , 56 ).…”

Dermal papilla cell-derived exosomes promote hair follicle regeneration during wound healing by activating Wnt/β‐catenin signaling pathway

“…The Wnt/β-catenin signaling pathway plays an important role in HF regeneration and wound healing [46][47][48]. Accumulating evidence has demonstrated that activation of the Wnt/β-catenin signaling pathway could promote wound healing [49,50]. During HF morphogenesis, the dermis provides the ' rst dermal signal' that initiates the formation of epidermal placodes, and sustained β-catenin activity in the dermis leads to larger HF placodes and accelerates differentiation of HFs [49,51].…”

Exploring the Role of Dermal Sheath Cells in Wound Healing and Fibrosis

“…The Wnt/β-catenin pathway is a well-known key player for enhancement of the overall healing process involving tissue regeneration via crosstalk with other signaling pathways [97]. The activation of the Wnt/β-catenin pathway elicits a range of healing responses, including the promotion of angiogenesis [98,99], enhancement of fibroblast migration, proliferation, and differentiation [1,97], stimulation of keratinocyte proliferation and differentiation [100,101], facilitation of re-epithelialization [102,103], and the induction of wound-induced hair folliculogenesis [104,105]. A cell tracing study reported that constitutive activation of β-catenin in DS not only generated ectopic hair follicle outgrowth, endowing DSCs with hair-inducing ability, but also induced cell-autonomous progressive skin fibrosis in the dermis, where the excessive fibroblasts largely originated from the DS [8].…”