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Updated: May 21, 2025

Murine Excisional Wound Healing Model and Histological Morphometric Wound Analysis
Published on: August 21, 2020
10-Methoxy-leonurine accelerated wound healing through ErbB4/PI3K-AKT pathway
Yue Zhang1, Bang-Yin Tan2, Hui-Zhen Peng3
1Yunnan Characteristic Plant Extraction Laboratory Co. Ltd, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, PR China.
Ethnopharmacological Relevance:
Leonurusjaponicus Houtt., commonly known as motherwort, has been used in traditional Chinese medicine to treat trauma and wound infections historically. However, the main compounds responsible for promoting wound healing need to be identified and explained fully.
Aim Of The Study:
To investigate the wound healing effect of 10-methoxy-leonurine (MN) and explore its mechanism.
Materials And Methods:
Following the UHPLC/Q-TOF-MS analysis of L. japonicus, the phytochemical isolation was carried out, and then the effect of isolated compounds in promoting the proliferation of human skin fibroblasts (HSF) was screened. Additionally, scratch and 5-ethynyl-2'-deoxyuridine assay in HSF were further adopted to support the effects of MN in vitro. A rat model with full-thickness skin wounds was used to verify in vivo by hematoxylin and eosin staining, Masson's trichrome and immunohistochemistry. Furthermore, network pharmacology and molecular docking were performed to predict the potential pathway, which were subsequently validated by cell cycle and RT-qPCR.
Results:
A total 11 compounds were isolated, in which MN exhibited the most significant bioactivity in promoting HSF proliferation and migration. Moreover, the wound healing rates in low (10 μg/mL) and high dose (50 μg/mL) of MN groups reached 93.9 % and 94.5 %, respectively, which was better than basic fibroblast growth factor (bFGF) 89.4 %. Additionally, the epithelial thickness, collagen Ⅰ deposition and α-smooth muscle actin expression were enhanced and the proportion of HSF cells in the S phase of the cell cycle was increased. Network pharmacological and molecular docking analysis suggested ErbB pathway was involved in the regulation of wound healing by MN, which was further supported by the up-regulation of Erbb4, Stat5, Pi3k, Akt and mTOR mRNA levels.
Conclusion:
MN showed potent effect on wound healing by regulating ErbB4/PI3K-AKT pathway, even better than bFGF.

