School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China.
School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China.
Biomed Pharmacother. 2023 Nov;167:115608. doi: 10.1016/j.biopha.2023.115608. Epub 2023 Oct 4.
Gelsemium elegans (Gardner & Chapm.) Benth (G. elegans) has been widely used as a traditional folk medicine in China and Southeast Asia. As the most abundant alkaloid in G. elegans, Koumine (KM) has been revealed the effect of inflammatory attenuation modulating by macrophage activation and polarization.
This study aimed to explore the effect of KM on modulation of microglia polarization that led to the suppression of neuroinflammation and further improved neurodegenerative behavior.
Inflammatory mediators, microglia M1 and M2 phenotype markers and Nrf2/HO-1 pathway related protein were assessed in LPS-induced BV2 cells and LPS-treated mice by RT-PCR, immunohistochemistry, immunofluorescence and Western blotting. Moreover, the learning and memory abilities of mice were evaluated by Morris water maze test, and the neuronal damage was evaluated by the Nissl staining.
KM attenuated LPS-induced viability and morphological changes in BV2 microglial cells. Our findings showed that KM activated the Nrf2/HO-1 signaling pathway to promote phenotypic switch from M1 to M2 phenotypes. This switch suppresses the release of inflammatory mediators in LPS-induced BV2 cells. Meanwhile, KM attenuated neuroinflammation through modulating microglia polarization and subsequently reversed the behavioral alterations in LPS-induced mice model of neuroinflammation.
KM may alleviate neuroinflammation by regulating microglia polarization with the involvement of Nrf2/HO-1 pathway, resulting of the neuroprotective effect.
钩吻（Gelsemium elegans （Gardner & Chapm.） Benth）作为一种传统的民间药物在中国和东南亚被广泛使用。作为钩吻中含量最丰富的生物碱，钩吻素甲（Koumine，KM）已被证实通过调节巨噬细胞的激活和极化来发挥抗炎作用。
本研究旨在探讨 KM 对小胶质细胞极化的调节作用，从而抑制神经炎症，进一步改善神经退行性行为。
采用 RT-PCR、免疫组织化学、免疫荧光和 Western blot 法检测 LPS 诱导的 BV2 细胞和 LPS 处理的小鼠中的炎症介质、小胶质细胞 M1 和 M2 表型标志物以及 Nrf2/HO-1 通路相关蛋白。此外，通过 Morris 水迷宫试验评估小鼠的学习和记忆能力，通过尼氏染色评估神经元损伤。
KM 减弱了 LPS 诱导的 BV2 小胶质细胞活力和形态变化。研究结果表明，KM 激活了 Nrf2/HO-1 信号通路，促进了从 M1 向 M2 表型的表型转换。这种转换抑制了 LPS 诱导的 BV2 细胞中炎症介质的释放。同时，KM 通过调节小胶质细胞极化减轻神经炎症，从而逆转 LPS 诱导的神经炎症小鼠模型中的行为改变。
KM 可能通过 Nrf2/HO-1 通路调节小胶质细胞极化来减轻神经炎症，从而发挥神经保护作用。
