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

被引:13
作者
Sun, Rui [1 ,5 ]
Liu, Chunyan [2 ,3 ,5 ]
Liu, Jian [1 ,2 ,3 ,5 ]
Yin, Siyuan [1 ,2 ,3 ,5 ]
Song, Ru [1 ,5 ]
Ma, Jiaxu [1 ,5 ]
Cao, Guoqi [1 ,5 ]
Lu, Yongpan [4 ,5 ]
Zhang, Guang [1 ,5 ]
Wu, Zhenjie [1 ,5 ]
Chen, Aoyu [2 ,3 ,5 ]
Wang, Yibing [1 ,2 ,3 ,4 ,5 ]
机构
[1] Shandong Univ, Shandong Prov Qianfoshan Hosp, Dept Plast Surg, Jinan 250012, Shandong, Peoples R China
[2] Shandong First Med Univ, Affiliated Hosp 1, Dept Plast Surg, Jinan 250014, Shandong, Peoples R China
[3] Shandong Prov Qianfoshan Hosp, Jinan 250014, Shandong, Peoples R China
[4] Shandong Univ Tradit Chinese Med, Clin Med Coll 1, Jinan 250014, Shandong, Peoples R China
[5] Jinan Clin Res Ctr Tissue Engn Skin Regenerat & Wo, Jinan 250014, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
NF-KAPPA-B; MOLECULAR DOCKING; IN-VITRO; INFLAMMATION; PROTEIN; MACROPHAGES; APOPTOSIS; GENE; ENVIRONMENT; MODULATION;
D O I
10.1038/s41598-022-26043-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:19
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