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Plant-derived exosome-like nanovesicles (ELNs) have emerged as promising candidates due to their diverse bioactive components with antioxidant, anti-inflammatory and regenerative properties. In this study, exosome-like nanovesicles (RhELNs) extracted from the root of Rhodiola rosea, a traditional Chinese medicine, were proved to have a good ability to promote the regeneration of vascular endothelial cells under hypoxia by EdU experiment and transwell experiment in vitro. After the treatment of mice with RhELNs injected into the tail vein, it was found that the inflammation level of the skeletal muscle of the mice was decreased, the degree of fibrosis was alleviated, the blood flow was restored, skeletal muscle atrophy and limb gangrene were improved. These results indicate that RhELNs can promote the recovery of ischemic skeletal muscle and angiogenesis. Furthermore, we identified a novel microRNA (novel-mirNA-115-5p) in RhELNs, which plays an important role in RhELNs. It protects vascular endothelial cells from mitochondrial damage by targeting TXNIP and it promotes vascular regeneration by reducing cellular pyroptosis under hypoxia conditions through inhibition of the TXNIP- NLRP3 pathway. These results suggest that RhELNs represent a promising new approach for treating lower limb skeletal muscle ischemic diseases.<\/jats:p>","DOI":"10.1093\/rb\/rbaf113","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:27:38Z","timestamp":1761744458000},"source":"Crossref","is-referenced-by-count":7,"title":["Rhodiola rosea-derived exosome-like nanovesicles inhibit vascular endothelial pyroptosis in the treatment of limb skeletal muscle ischemic injury through the TXNIP\/NLNP3 pathway"],"prefix":"10.1093","volume":"12","author":[{"given":"Dachang","family":"Liu","sequence":"first","affiliation":[{"name":"School of Medicine, Nankai University , Tianjin 300071,","place":["China"]},{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin University Central Hospital; Department of Heart Center, The Third Central Hospital of Tianjin; Nankai University Affiliated Third Center Hospital; The Third Central Clinical College of Tianjin Medical University, Tianjin 300170,","place":["China"]},{"name":"Senior Department of Orthopedics, The Fourth Medical Centre, Chinese PLA Hospital , Beijing 100048,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University , Tianjin 300071,","place":["China"]},{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin University Central Hospital; Department of Heart Center, The Third Central Hospital of Tianjin; Nankai University Affiliated Third Center Hospital; The Third Central Clinical College of Tianjin Medical University, Tianjin 300170,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchao","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University , Tianjin 300071,","place":["China"]},{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin University Central Hospital; Department of Heart Center, The Third Central Hospital of Tianjin; Nankai University Affiliated Third Center Hospital; The Third Central Clinical College of Tianjin Medical University, Tianjin 300170,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University , Tianjin 300071,","place":["China"]},{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin University Central Hospital; Department of Heart Center, The Third Central Hospital of Tianjin; Nankai University Affiliated Third Center Hospital; The Third Central Clinical College of Tianjin Medical University, Tianjin 300170,","place":["China"]},{"name":"Tianjin ECMO Treatment and Training Base, Tianjin 300170, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University , Tianjin 300071,","place":["China"]},{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin University Central Hospital; Department of Heart Center, The Third Central Hospital of Tianjin; Nankai University Affiliated Third Center Hospital; The Third Central Clinical College of Tianjin Medical University, Tianjin 300170,","place":["China"]},{"name":"Tianjin ECMO Treatment and Training Base, Tianjin 300170, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changduo","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Advanced Medical Materials and Devices, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin 300192,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaming","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Advanced Medical Materials and Devices, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin 300192,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University , Tianjin 300071,","place":["China"]},{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin University Central Hospital; Department of Heart Center, The Third Central Hospital of Tianjin; Nankai University Affiliated Third Center Hospital; The Third Central Clinical College of Tianjin Medical University, Tianjin 300170,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin University Central Hospital; Department of Heart Center, The Third Central Hospital of Tianjin; Nankai University Affiliated Third Center Hospital; The Third Central Clinical College of Tianjin Medical University, Tianjin 300170,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin University Central Hospital; Department of Heart Center, The Third Central Hospital of Tianjin; Nankai University Affiliated Third Center Hospital; The Third Central Clinical College of Tianjin Medical University, Tianjin 300170,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hechen","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China , Chengdu 610000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University , Tianjin 300071,","place":["China"]},{"name":"Senior Department of Orthopedics, The Fourth Medical Centre, Chinese PLA Hospital , Beijing 100048,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4824-3489","authenticated-orcid":false,"given":"Wenqing","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University , Tianjin 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