Molecular docking and molecular dynamics simulation study the mechanism of progesterone in the treatment of spinal cord injury

• Published in: Steroids 2022-12, Vol.188, p.109131-109131, Article 109131
• Main Authors: Yang, Xingyu, Cao, Jun-Feng, Chen, Shengyan, Xiong, Li, Zhang, Lixin, Wu, Mei, Wang, Chaochao, Xu, Hengxiang, Chen, Yijun, Yang, Siqi, Zhong, Li, Wei, Xiaoliang, Xiao, Zixuan, Gong, Yunli, Li, Yang, Zhang, Xiao
• Format: Article
• Language: English
• Subjects: Bioinformatics analysis; Humans; Inflammation - drug therapy; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; Pharmaceutical Preparations; Progesterone; Progesterone - metabolism; Progesterone - pharmacology; Progesterone - therapeutic use; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - metabolism; Spinal cord injury
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2022.109131

[Display omitted] •Progesterone promotes neuronal regeneration by regulating the BDNF-TrkB-ERK-CREB signaling pathway.•Progesterone promotes remyelination by acting on AR or by promoting androgen release.•Progesterone acts on NGF to control the MAPK/ERK, PI3K/Akt and PLC-γ pathways, thereby regulating the level of inflammation.•Progesterone reduces the expression of TNF-α through the NF-kB pathway, thereby promoting the repair of spinal cord injury. Spinal cord injury can lead to incomplete or complete loss of voluntary movement and sensory function, leading to serious complications. Numerous studies have shown that progesterone exhibits strong therapeutic potential for spinal cord injury. However, the mechanism by which progesterone treats spinal cord injury remains unclear. Therefore, this article explores the mechanism of progesterone in the treatment of spinal cord injury by means of molecular docking and molecular dynamics simulation. We used bioinformatics to screen active pharmaceutical ingredients and potential targets, and molecular docking and molecular dynamics were used to validate and analysis by the supercomputer platform. Progesterone had 3606 gene targets, spinal cord injury had 6560 gene targets, the intersection gene targets were 2355. GO and KEGG analysis showed that the abundant pathways involved multiple pathways related to cell metabolism and inflammation. Molecular docking showed that progesterone played a role in treating spinal cord injury by acting on BDNF, AR, NGF and TNF. Molecular dynamics was used to prove and analyzed the binding stability of active ingredients and protein targets, and AR/Progesterone combination has the strongest binding energy. Progesterone promotes recovery from spinal cord injury by promoting axonal regeneration, remyelination, neuronal survival and reducing inflammation.