Traumatic brain injury (TBI) is a pathology of great social impact, affecting millions of people worldwide. Despite the scientific advances to improve the management of TBI in recent years, we still do not have a specific treatment that controls the inflammatory process after mechanical trauma. The discovery and implementation of new treatments is a long and expensive process, making the repurpose of approved drugs for other pathologies a clinical interest. Tibolone is a drug in use for the treatment of symptoms associated with menopause and has been shown to have a broad spectrum of actions by regulating estrogen, androgen and progesterone receptors, whose activation exerts potent anti-inflammatory and antioxidant effects. In the present study, we aimed to investigate the therapeutic potential of the tibolone metabolites 3α-Hydroxytibolone, 3β-Hydroxytibolone, and Δ4-Tibolone as a possible therapy in TBI using network pharmacology and network topology analysis. Our results demonstrate that the estrogenic component mediated by the α and β metabolites can regulate synaptic transmission and cell metabolism, while the Δ metabolite may be involved in modulating the post-TBI inflammatory process. We identified several molecular targets, including , , , , , and , which are known to play critical roles in the pathogenesis of TBI. Tibolone metabolites were predicted to regulate the expression of key genes involved in oxidative stress, inflammation, and apoptosis. Overall, the repurposing of tibolone as a neuroprotective treatment for TBI holds promise for future clinical trials. However, further studies are needed to confirm its efficacy and safety in TBI patients.

中文翻译：

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替勃龙代谢物及其治疗脑外伤的分子机制的网络药理学和拓扑分析


创伤性脑损伤（TBI）是一种具有巨大社会影响的病理学，影响着全世界数百万人。尽管近年来在改善 TBI 治疗方面取得了科学进步，但我们仍然没有控制机械创伤后炎症过程的具体治疗方法。新疗法的发现和实施是一个漫长而昂贵的过程，这使得将已批准的药物重新用于其他疾病引起了临床兴趣。替勃龙是一种用于治疗与更年期相关症状的药物，已被证明通过调节雌激素、雄激素和孕激素受体而具有广泛的作用，其激活可发挥有效的抗炎和抗氧化作用。在本研究中，我们旨在利用网络药理学和网络拓扑分析，研究替勃龙代谢物 3α-羟基替勃龙、3β-羟基替勃龙和 Δ4-替勃龙作为 TBI 可能疗法的治疗潜力。我们的结果表明，α和β代谢物介导的雌激素成分可以调节突触传递和细胞代谢，而Δ代谢物可能参与调节TBI后炎症过程。我们确定了几个分子靶点，包括 、 、 、 、 和 ，已知它们在 TBI 的发病机制中发挥关键作用。预计替勃龙代谢物可调节参与氧化应激、炎症和细胞凋亡的关键基因的表达。总体而言，替勃龙重新用作 TBI 的神经保护治疗方法为未来的临床试验带来了希望。然而，还需要进一步的研究来证实其对 TBI 患者的有效性和安全性。