Xu Min, Shi Zhenhua, He Ziyang, Ling Xiaoyang, Wang Wenhua, Liu Hua, Gong Mingjie
Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan 215300, Jiangsu Province, China.
Department of Neurosurgery, Changshu No.2 People's Hospital, The Affiliated Changshu Hospital of Nantong University, 215500 Jiangsu Province, China.
Biomed Pharmacother. 2023 Oct;166:115300. doi: 10.1016/j.biopha.2023.115300. Epub 2023 Aug 7.
Due to its widespread prevalence, migraine is a common neurovascular condition that has a major impact on people's health and quality of life. Rutaecarpine (RUT) is one of the main effective components of Evodia rutaecarpa, which has a wide range of biological activities. However, the exact mechanism by which RUT improves migraine remain unknown.
The purpose of this study was to investigate whether RUT improves migraine by inhibiting oxidative stress via activating the Nrf2 antioxidant system through the PTEN/PGK1 signaling pathway.
In vivo, a mouse model of chronic migraine (CM) was established by repeated intraperitoneal injection of nitroglycerin (NTG). After treatment with RUT and Sumatriptan, behavioral tests were performed, followed by measurements of oxidative stress-related indicators in the trigeminal nucleus caudalis, expression of proteins associated with the Nrf2 antioxidant system, and the PTEN/PGK1 pathway. In vitro, PC12 cells were stimulated by 100 μM H2O2 for 24 h to induce oxidative stress, which was then treated with RUT. Furthermore, the role of PTEN in antioxidant stress of RUT was elucidated by knockout of the PTEN gene.
The results showed that RUT treatment improved NTG-induced migraine in mice by inhibiting oxidative stress. Importantly, RUT inhibited oxidative stress in NTG-induced mice or H2O2-induced PC12 cells via activating the Nrf2 antioxidant system by inhibiting PGK1 activity through PTEN. These results provide evidence that RUT improves migraine by activation of the Nrf2 antioxidant system through the PTEN/PGK1 pathway and provide new insights into the potential use of RUT as an effective drug development candidate for migraine.
偏头痛因其广泛流行，是一种常见的神经血管疾病，对人们的健康和生活质量有重大影响。吴茱萸次碱（RUT）是吴茱萸的主要有效成分之一，具有广泛的生物活性。然而，RUT改善偏头痛的确切机制尚不清楚。
本研究旨在探讨RUT是否通过PTEN/PGK1信号通路激活Nrf2抗氧化系统来抑制氧化应激，从而改善偏头痛。
在体内，通过反复腹腔注射硝酸甘油（NTG）建立慢性偏头痛（CM）小鼠模型。用RUT和舒马曲坦治疗后，进行行为测试，随后测量三叉神经尾核中氧化应激相关指标、Nrf2抗氧化系统相关蛋白的表达以及PTEN/PGK1通路。在体外，用100μM H2O2刺激PC12细胞24小时以诱导氧化应激，然后用RUT处理。此外，通过敲除PTEN基因阐明PTEN在RUT抗氧化应激中的作用。
结果表明，RUT治疗通过抑制氧化应激改善了NTG诱导的小鼠偏头痛。重要的是，RUT通过PTEN抑制PGK1活性，激活Nrf2抗氧化系统，从而抑制NTG诱导的小鼠或H2O2诱导的PC12细胞中的氧化应激。这些结果证明RUT通过PTEN/PGK1途径激活Nrf2抗氧化系统来改善偏头痛，并为RUT作为偏头痛有效药物开发候选物的潜在用途提供了新的见解。
