Exploration of the effect and potential mechanism of quercetin in repairing spinal cord injury based on network pharmacology and in vivo experimental verification
Wenyuan Shen,
Quan Liu,
Chuanhao Li,
Muhetidier Abula,
Zibo Yang,
Zhishuo Wang,
Jun Cai,
Xiaohong Kong
Affiliations
Wenyuan Shen
International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China; Department of Orthopedics, The Second Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Street, Jinan, Shandong, China; Orthopedic Research Center of Shandong University &Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
Quan Liu
International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
Chuanhao Li
International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
Muhetidier Abula
International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China; Department of Orthopedics, Hotan Prefecture People's Hospital, Hotan, Xinjiang, 848000, China
Zibo Yang
Tianjin Medicine and Health Research Center, Tianjin Institute of Medical & Pharmaceutical Sciences, Tianjin, 300020, China
Zhishuo Wang
International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
Jun Cai
Tianjin Medicine and Health Research Center, Tianjin Institute of Medical & Pharmaceutical Sciences, Tianjin, 300020, China; Corresponding author.
Xiaohong Kong
Orthopedic Research Center of Shandong University &Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Corresponding author.
Spinal cord injury (SCI) is a highly complex neurological disease, but there is no effective repair method. Quercetin is a flavonol drug and has a variety of biological activities, such as scavenging oxygen free radicals in the body to resist oxidation, inhibiting inflammation, and so on. In this study, quercetin was firstly demonstrated to reduce tissue damage, promote neuron survival and repair motor function after SCI in rats through in vivo experiments. Then, 293 potential targets of quercetin repair for SCI were predicted by network pharmacology. GO analysis revealed that the biological processes of potential targets focused mainly on signal transduction, negative regulation of the apoptotic process, protein phosphorylation, drug response, and so on. Similarly, KEGG analysis suggested that these potential targets were involved in cell growth regulation, differentiation, apoptosis, and a few metabolic pathways. PPI network analysis predicted that the key genes were EP300, CREBBP, SRC, HSP90AA1, TP53, PIK3R1, EGFR, ESR1, and CBL. Further, the molecular docking showed that quercetin binds well with these proteins. Finally, RT-qPCR and Western blotting experiments verified that quercetin downregulated the expression levels of PIK3R1 and EGFR. It is suggested that quercetin can repair SCI in rats through PI3K-AKT signaling pathway and EGFR/MAPK pathway, which may provide a new theoretical basis for the repair of spinal cord injury.
