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



Saberi Shahrbabaki A ; Amini B ; Ghorbani M ; Ghasemi M ; Ganjizadeh S ; Khoushehmehr SM ; Rahmani A ; Azizi H ; Delnavazi MR
Source: Natural Product Communications Published:2025

Abstract

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. © The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).