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Integrating bioinformatic prediction and the "gut microbiota-inflammation-skin axis" to decipher the mechanisms of quercetin (from Evodia rutaecarpa) in diabetic wound healing

文献类型：期刊论文

作者Huang, Zhixuan4,5; Liu, Jian4,5; Zheng, Xu3; Geng, Xinrong2; Tan, Jinlong4,5; Ai, Yangwen4,5; Li, Hui1,4,5; Zhou, Dongyue4,5
刊名FRONTIERS IN IMMUNOLOGY
出版日期2026-02-24
卷号17页码:27
关键词bioinformatics analysis diabetic foot ulcer fecal microbiotatransplantation gut-skin axis quercetin
ISSN号1664-3224
DOI10.3389/fimmu.2026.1755280
通讯作者Li, Hui(lihuiyiren@163.com) ; Zhou, Dongyue(zhoudongyue@itcmhi.ac.cn)
英文摘要Background Diabetic foot ulcer (DFU) is a serious complication of diabetes with impaired healing. This study focused on the herbal medicine Evodia rutaecarpa as a case to investigate the mechanisms of diabetic wound healing via the "gut microbiota-inflammation-skin axis". We specifically aimed to elucidate the role of its core bioactive flavonoid, quercetin (Que), whose therapeutic potential in this context remains underexplored.Methods In vitro, the direct interaction between Que and HIF1 alpha was assessed by cellular thermal shift assay, and its functional effect on the HIF1 alpha/VEGF pathway was evaluated in a lipopolysaccharide-induced RAW264.7/HUVEC co-culture system. In vivo, a streptozotocin-induced diabetic rat model with full-thickness dorsal wounds was treated with Que. Wound healing rates, metabolic parameters, systemic inflammation, and gut microbiota composition were analyzed. The causal role of the gut microbiota was further tested using fecal microbiota transplantation from Que-treated donors to diabetic recipient rats, and the biological activity of resulting drug-containing serum was assessed in HUVEC and RAW264.7 cell cultures.Results Que was identified as a principal active component of E. rutaecarpa with predicted binding affinity for key targets involved in inflammatory and hypoxic responses. In vitro, Que directly bound to and stabilized HIF1 alpha protein and upregulated the expression of both HIF1 alpha and VEGF in HUVECs under inflammatory co-culture conditions. In diabetic rats, Que treatment significantly accelerated wound closure, improved systemic glucose and lipid metabolism, reduced serum levels of TNF-alpha and IL-1 beta, and modulated the gut microbiota structure. FMT from Que-treated rats replicated the pro-healing effects, enhancing angiogenesis and collagen deposition in wounds, and reducing tissue inflammation. Consistently, serum derived from the FMT-Que group promoted HUVEC migration and tube formation, and attenuated the pro-inflammatory cytokine expression in RAW264.7 cells.Conclusion This study demonstrated that Que promoted diabetic wound healing by modulating the "gut microbiota-inflammation-skin axis", thereby reducing systemic inflammation and enhancing local angiogenesis.
WOS关键词TRADITIONAL CHINESE MEDICINE
WOS研究方向Immunology
语种英语
WOS记录号WOS:001709966800001
资助机构Fundamental Research Funds for the Central Public Welfare Research Institutes ; Natural Science Foundation of Jiangxi Province ; General Project of Jiangxi Provincial Administration of Traditional Chinese Medicine
源URL[http://ir.yic.ac.cn/handle/133337/42255]  
专题烟台海岸带研究所_中科院烟台海岸带研究所知识产出
通讯作者Li, Hui; Zhou, Dongyue
作者单位1.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing, Peoples R China
2.Chinese Acad Sci, Yantai Inst Coastal Zone Res, Yantai, Shandong, Peoples R China
3.Henan Univ Chinese Med, Affiliated Hosp 1, Dept Tuina, Zhengzhou, Peoples R China
4.Jiangxi Hlth Ind Inst Tradit Chinese Med, Nanchang, Peoples R China
5.China Acad Chinese Med Sci, Inst Tradit Chinese Med Hlth Ind, Jiangxi Prov Key Lab Tradit Chinese Med Pharmacol, Nanchang, Peoples R China
推荐引用方式
GB/T 7714		 Huang, Zhixuan,Liu, Jian,Zheng, Xu,et al. Integrating bioinformatic prediction and the "gut microbiota-inflammation-skin axis" to decipher the mechanisms of quercetin (from Evodia rutaecarpa) in diabetic wound healing[J]. FRONTIERS IN IMMUNOLOGY,2026,17:27.
APA Huang, Zhixuan.,Liu, Jian.,Zheng, Xu.,Geng, Xinrong.,Tan, Jinlong.,...&Zhou, Dongyue.(2026).Integrating bioinformatic prediction and the "gut microbiota-inflammation-skin axis" to decipher the mechanisms of quercetin (from Evodia rutaecarpa) in diabetic wound healing.FRONTIERS IN IMMUNOLOGY,17,27.
MLA Huang, Zhixuan,et al."Integrating bioinformatic prediction and the "gut microbiota-inflammation-skin axis" to decipher the mechanisms of quercetin (from Evodia rutaecarpa) in diabetic wound healing".FRONTIERS IN IMMUNOLOGY 17(2026):27.

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来源：烟台海岸带研究所

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