Mechanisms of action underlying the effect of Tongsaimai on wound healing based on experimental and network pharmacology

伤口愈合 哈卡特 药理学 血管生成 PI3K/AKT/mTOR通路 医学 炎症 化学 信号转导 体外 癌症研究 生物化学 免疫学
作者
Fanxing Xu,Jingxian Wu,Yumei Hu,Chun Chu,Wenjun Liu,Xiang Li,Zheng Wen,Weishuo Yang,Zhao Boyan,Jiangxue Guo,Zhenzhong Wang,Ying Jia,Wei Xiao
出处
期刊:Journal of Ethnopharmacology [Elsevier BV]
卷期号:311: 116451-116451 被引量:3
标识
DOI:10.1016/j.jep.2023.116451
摘要

Tongsaimai (TSM) is a traditional Chinese medicine that has several therapeutic qualities, including anti-inflammatory, anti-oxidative, and anti-vasculitis effects. However, its impacts and underlying mechanisms on wound healing remain unclear. The aim of our study was to evaluate TSM for its pro-healing effect and the relevant mechanisms using both experimental validation and network pharmacology analysis. The components of TSM were detected by high-performance liquid chromatography combined with diode array detector (HPLC-DAD). Skin wounds with a diameter of 4 mm were created on the backs of mice, after which, topical treatments of 2.5–10% TSM were applied onto the lesions once daily for either 2 or 7 days. Then, the wound tissues were collected to determine the impacts of TSM on collagen deposition, epithelial cell proliferation, oxidative stress, inflammation, and angiogenesis. Moreover, the effects of TSM (0.5–2 mg/mL) on the cell viability of HUVECs and HaCaT cells were evaluated. A total of 11 components in TSM were identified by HPLC-DAD. TSM was found to enhance the rate of wound contraction and increase epithelial thickness and collagen deposition during the healing process. In addition, TSM increased SOD activity and downregulated MDA and IL-1β levels in the wound tissues. Immunofluorescence analysis further indicated an increased expression of Ki67, CD31, and VEGF in wound tissues following TSM administration. Results of the network pharmacology analysis revealed that multiple pathways including VEGF, PI3K/Akt, and MAPK pathways were involved in the pharmacological actions of TSM on wound healing. Accordantly, in vitro experiments revealed that TSM promoted the proliferation of HUVECs and HaCaT cells while activating the PI3K/Akt pathway. Our results suggest that TSM may serve as a therapeutic medication to improve wound healing by employing multiple regulatory mechanisms that affect proliferation, angiogenesis, collagen deposition, oxidative stress, and inflammation.
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