Shikonin inhibits ER stress in vascular endothelial cells, when induced by H₂O₂, and promotes vascular regeneration

Lili Guo^a,?, Yinling Li^b,c,?, Shuang Wen^b, Wen jun Liu^d, Lei Yang^a, Yu Wan^a, Jia xin Liu^a, Wen e Zhao^e,, Shu-Wei Li^a,

ABSTRACT: Shikonin is a naphthoquinone compound. Various reports proved that shikonin not only has anticancer and antibacterial effects, but also can play a certain role in promoting wound healing. However, whether shikonin can reduce oxidative stress degree in endothelial cells of vascular and reconstruct the lining of damaged vessels is unknown. Therefore, we used a variety of biological techniques to study the function of shikonin in protecting endothelial cells at the animal and cellular levels. Our study showed that oxidative stress was significantly enriched in the endoplasmic reticulum (ER). Thus, shikonin can effectively resist ER stress and inhibit inflammation and apoptosis of endothelial cells. More importantly, we also found that shikonin can inhibit stress by regulating janus kinase2-signal transducers and activators of transcription3 (JAK2/STAT3) pathways, thereby protecting endothelial cells from H2O2 -induced damage. In addition, the application of shikonin to skin wounds in mice can also promote the expression of vascular endothelial growth factor (VEGF) proteins in vascular endothelial cells; hence promoting the reconstruction of wounded blood vessels and providing a proper blood supply, thus accelerating wound healing. In conclusion, our research findings provide the groundwork for future clinical treatments of skin wounds and related research.

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^a	Xinjiang Production & Construction Corps Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin, College of Life Science and Technology, Tarim University, Xinjiang 843300 China
^b	Department of Immunology, Nanjing Medical University, Jiangsu 211166 China
^c	The First Affiliated Hospital of Nanjing Medical University, Jiangsu 211166 China
^d	Department of Pharmacology, School of Basic Medical Science, Nanjing Medical University, Jiangsu 211166 China
^e	School of Basic Medical Science, Nanjing Medical University, Jiangsu 211166 China

* Corresponding author, E-mail: zwe99@njmu.edu.cn, Tarim_yfzx406@126.com

Received 5 Oct 2022, Accepted 18 Mar 2023

Shikonin inhibits ER stress in vascular endothelial cells, when induced by H2O2, and promotes vascular regeneration

Lili Guoa,?, Yinling Lib,c,?, Shuang Wenb, Wen jun Liud, Lei Yanga, Yu Wana, Jia xin Liua, Wen e Zhaoe,*, Shu-Wei Lia,*

Shikonin inhibits ER stress in vascular endothelial cells, when induced by H₂O₂, and promotes vascular regeneration

Lili Guo^a,?, Yinling Li^b,c,?, Shuang Wen^b, Wen jun Liu^d, Lei Yang^a, Yu Wan^a, Jia xin Liu^a, Wen e Zhao^e,, Shu-Wei Li^a,