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  3. Integrated network pharmacology and experimental validation to explore the mechanisms underlying naringenin treatment of chronic wounds

Integrated network pharmacology and experimental validation to explore the mechanisms underlying naringenin treatment of chronic wounds

  • Sci Rep. 2023 Jan 4;13(1):132. doi: 10.1038/s41598-022-26043-y.
Rui Sun 1 2,  Chunyan Liu 3 2,  Jian Liu 1 3 2,  Siyuan Yin 1 3 2,  Ru Song 1 2,  Jiaxu Ma 1 2,  Guoqi Cao 1 2,  Yongpan Lu 4 2,  Guang Zhang 1 2,  Zhenjie Wu 1 2,  Aoyu Chen 3 2,  Yibing Wang 5 6 7 8
Affiliations

Affiliations

  • 1 Department of Plastic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250012, People's Republic of China.
  • 2 Jinan Clinical Research Center for Tissue Engineering Skin Regeneration and Wound Repair, Jinan, Shandong, 250014, People's Republic of China.
  • 3 Department of Plastic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, 250014, People's Republic of China.
  • 4 The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250014, People's Republic of China.
  • 5 Department of Plastic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250012, People's Republic of China. ybwang@sdfmu.edu.cn.
  • 6 Department of Plastic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, 250014, People's Republic of China. ybwang@sdfmu.edu.cn.
  • 7 The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250014, People's Republic of China. ybwang@sdfmu.edu.cn.
  • 8 Jinan Clinical Research Center for Tissue Engineering Skin Regeneration and Wound Repair, Jinan, Shandong, 250014, People's Republic of China. ybwang@sdfmu.edu.cn.
PMID: 36599852 DOI: 10.1038/s41598-022-26043-y
Abstract

Naringenin is a citrus flavonoid with various biological functions and a potential therapeutic agent for skin diseases, such as UV radiation and atopic dermatitis. The present study investigates the therapeutic effect and pharmacological mechanism of naringenin on chronic wounds. Using network pharmacology, we identified 163 potential targets and 12 key targets of naringenin. Oxidative stress was confirmed to be the main biological process modulated by naringenin. The transcription factor p65 (RELA), alpha serine/threonine-protein kinase (Akt1), mitogen-activated protein kinase 1 (MAPK1) and mitogen-activated protein kinase 3 (MAPK3) were identified as common targets of multiple pathways involved in treating chronic wounds. Molecular docking verified that these four targets stably bound naringenin. Naringenin promoted wound healing in mice in vivo by inhibiting wound inflammation. Furthermore, in vitro experiments showed that a low naringenin concentration did not significantly affect normal skin cell viability and cell apoptosis; a high naringenin concentration was cytotoxic and reduced cell survival by promoting Apoptosis. Meanwhile, comprehensive network pharmacology, molecular docking and in vivo and in vitro experiments revealed that naringenin could treat chronic wounds by alleviating oxidative stress and reducing the inflammatory response. The underlying mechanism of naringenin in chronic wound therapy involved modulating the RELA, Akt1 and MAPK1/3 signalling pathways to inhibit ROS production and inflammatory cytokine expression.

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