2. Academic Validation
  3. Nuciferine improves random skin flap survival via TFEB-mediated activation of autophagy-lysosomal pathway

Nuciferine improves random skin flap survival via TFEB-mediated activation of autophagy-lysosomal pathway

  • Int Immunopharmacol. 2023 Apr 29;119:110204. doi: 10.1016/j.intimp.2023.110204.
Kaikai Xue 1,  Guojian Zhang 1,  Yiwei Zhou 2,  Kangyan Wang 3,  Zhe Yao 1,  Jinghao Chen 3,  Yu Zhang 3,  Zihao Li 1,  Zi Li 3,  Zimin Zheng 4,  Yongzeng Feng 3,  Cong Mao 5,  Cai Lin 6,  Weidong Xia 7
Affiliations

Affiliations

  • 1 Department of Burn, Wound Repair and Regenerative Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Zhejiang Provincial Key Laboratory of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
  • 2 Department of Traditional Chinese Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 3 Zhejiang Provincial Key Laboratory of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
  • 4 Zhejiang Provincial Key Laboratory of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, China.
  • 5 Zhejiang Provincial Key Laboratory of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. Electronic address: maocong@wmu.edu.cn.
  • 6 Department of Burn, Wound Repair and Regenerative Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: 13025092850@163.com.
  • 7 Department of Burn, Wound Repair and Regenerative Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: jason1989119@126.com.
PMID: 37126988 DOI: 10.1016/j.intimp.2023.110204
Abstract

Due to their simplicity and reliability, random-pattern skin flaps are commonly utilized in surgical reconstruction to repair cutaneous wounds. However, the post-operative necrosis frequently happens because of the ischemia and high-level of oxidative stress of random skin flaps, which can severely affect the healing outcomes. Earlier evidence has shown promising effect of Nuciferine (NF) on preventing hydrogen peroxide (H2O2)-induced fibroblast senescence and ischemic injury, however, whether it can function on promoting ischemic FLAP survival remains unknown. In this work, using network pharmacology analysis, it was possible to anticipate the prospective targets of NF in the context of ischemia. The results revealed that NF treatment minimized H2O2-induced cellular dysfunction of human umbilical vein endothelial cells (HUVECs), and also improved FLAP survival through strengthening angiogenesis and alleviating oxidative stress, inflammation and Apoptosis in vivo. These outcomes should be attributed to TFEB-mediated enhancement of autophagy-lysosomal degradation via the AMPK-mTOR signaling pathway, whilst the restriction of Autophagy stimulation with 3MA effectively diminished the above advantages of NF treatment. The increased nuclear translocation of TFEB not only restored lysosome function, but also promoted autophagosome-lysosome fusion, eventually restoring the inhibited autophagic flux and filling the high energy levels. The outcomes of our research can provide potent proof for the application of NF in the therapy of vascular insufficiency associated disorders, including random flaps.

Keywords

Angiogenesis; Autophagy-lysosomal pathway; Oxidative stress; Random skin flaps; TFEB.

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