ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Tripterine from Tripterygium wilfordii exosome accelerated diabetic wound healing by improving endothelial cell function
Provisionally accepted
Mingming Jin1*
Yao Chen1Zhixian Zhang1
Yuhan Wang1Tailei Yuan2Maolin Xia1
Menghan Wang1Xue Li1Gang Huang1Hong Sun2- 1Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
- 2Nanjing Jiangbei Hospital, Nanjing, China
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Background: Diabetic wounds (DWs) are a severe complication of diabetes mellitus, which lead to persistent infection, amputation, and even mortality. Accumulating reports indicated that mesenchymal stem cell-originating exosomes (Exo) provide a candidatemethod for DW repair. Nevertheless, source restrictions, includinga rapid decrease of biological activity,and unknown biological mechanisms limit clinical application of Exo. Methods: In this study, we isolated Tripterygium wilfordii (TRI)-originating Exo (TRI-Exo). TRI-Exo treatment inhibited stress microenvironment-induced endothelial cell damage and accelerated DW healing. Mass spectrometry for TRI-Exo active constituent detection showed that TRI-Exo contain tripterine (TRI). Both in vivo and in vitro experiments confirmed that TRI treatment reversed stress microenvironment-induced endothelial cell damage and promoted DW healing. Results: Transmission electron micrography detection similarly showed that TRI-Exo were approximately 120 nm and that they had a cup- or sphere-shaped morphology. Fluorescence microscopy detection indicated that PKH67-labeled TRI-Exo could be taken up by HUVECs. High-throughput sequencing, biotin-TRI RNA-pulldown, and LiP-SMap analysis found that mitogen-activated protein kinase kinase 1 (MAP2K1) was a downstream target of TRI. MAP2K1 overexpression reversed the protective effect of TRI against LPS-induced HUVEC dysfunction by regulating NKκB/HO-1/VEGF-mediated ROS production, the inflammatory response, and angiogenesis. Conclusion: Taken together, we found that TRI from TRI exosome treatment improved the hyperglycemic-induced stress microenvironment by direct binding to and inhibition of MAP2K1, thereby improving endothelial cell function and accelerating DW healing.
Keywords: diabetic wound healing, Endothelial Cells, exosome, ROS, Tripterine, Tripterygium wilfordii
Received: 29 Sep 2025; Accepted: 02 Jan 2026.
Copyright: © 2026 Jin, Chen, Zhang, Wang, Yuan, Xia, Wang, Li, Huang and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mingming Jin
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