Background

Wound healing progresses through phases of homeostasis, inflammation, proliferation, and remodeling, regulated by signaling pathways. The root extract of Onosma microcarpum (OM), traditionally used in Western Iran for wound care, contains bioactive compounds like alkannin, shikonin, and polyphenols, potentially enhancing healing. This study evaluates OM's effects on wound healing through the signaling pathways in each phase.

Methods

Dried OM root was formulated into ointments, and male Wistar rats with excisional wounds were treated with OM (0.2% or 1%) or vehicle. Wound closure rate, histological and gene expression analyses were conducted on days 3, 8, and 14, measuring inflammation, granulation, angiogenesis, and collagen formation. The mRNA expression of cytokines (Interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α)), growth factors (Transforming Growth Factor-β1 (TGF-β1), platelet-derived growth factor (PDGF)), and cell regulators (extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK), p38 mitogen-activated protein kinase (p38 MAPK)) were analyzed.

Results

OM at 0.2%, significantly modulated key pathways in wound healing. By day 3, OM reduced TNF-α (P = 0.003) and IL-1β (P = 0.008), decreasing inflammation and JNK activity (P = 0.009). On day 8, OM further reduced IL-6 (P = 0.002) and p38 MAPK (P = 0.005) while increasing TGF-β1 (P = 0.008) and PDGF (P = 0.001), promoting proliferation. By day 14, increased ERK (P = 0.008) and p38 MAPK (P = 0.002) activity facilitated tissue repair. Wounds treated with 0.2% OM showed better outcomes than 1%, with more organized collagen (mean score 3.0 vs 2.3, P = 0.021), improved angiogenesis (3.4 vs 2.5, P = 0.038), and higher wound closure (87% vs 69%, P = 0.023).

Conclusion

OM enhances wound healing by targeting each phase: reducing early inflammation, promoting mid-phase fibroblast proliferation, and supporting collagen organization in remodeling. These targeted effects suggest OM's therapeutic potential for wound repair.

Search results

Dose-Specific Modulation of Signaling Pathways by Extract of Onosma microcarpum During Distinct Phases of Wound Healing in a Rat Model

Search results

Dose-Specific Modulation of Signaling Pathways by Extract of Onosma microcarpum During Distinct Phases of Wound Healing in a Rat Model