Arglabin regulates microglia polarization to relieve neuroinflammation in Alzheimer's disease.

Yi Yang, Li Guo, Jin Wang, WenYan Li, Xiaohong Zhou, Caiqun Zhang, Chenyang Han

Journal of biochemical and molecular toxicology 2022 Jun

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Arglabin (Arg) is a derivative of parthenolide. At present, there are few reports on the pharmacological effects and targets of Arg. In this study, we aimed to explore the relationship between Arg and NF-κB (P50) and the intervention effects of Arg on neuroinflammation. BV2 cells were cultured in vitro. LPS/IFN-γ was used to induce M1 polarization. After Arg intervention, the cytokine expression of M1 and M2 cell marker was detected, the expression of CD86 was detected by immunofluorescence (IF) staining, the levels of P50 and p-P50 were detected by Western blot and the expression of ROS was by DCFH-DA. AfterP50 knockout, we investigated the effect of P50 on the polarization of BV2 cells. Four-month-old APP/PS1 (AD) mice were treated with Arg by intragastric administration, followed by detection of the expression of CD86, CD206, and IBA-1 by IF staining, Finally, molecular-protein docking and Pull-down assays were used to validate the targeted binding relationship between P50 and Arg. Arg could inhibit the M1 polarization of BV2 cells, decrease the levels of TNF-α, IL-1β, IL-6, iNOS, and IL-12, and simultaneously inhibit the expression of P50 and p-P50. P50 knockout could inhibit the M1 polarization of BV2 cells, and P50 played an important role in the polarization of BV2 cells. Molecular docking and pull-down assays revealed that Arg and P50 had a targeted binding relationship. Animal experiments showed that Arg could regulate the polarization level of M1-M2 cells, increase the proportion of M2 cells, decrease the degree of nerve injury and suppress the expression of P50 and p-P50. In this study, we found that Arg could target P50 to regulate reprogramming of BV2 cells, inhibit M1 polarization, and increase the level of M2 cells, thereby exerting a neuroprotective effect. © 2022 Wiley Periodicals LLC.

Citation

Yi Yang, Li Guo, Jin Wang, WenYan Li, Xiaohong Zhou, Caiqun Zhang, Chenyang Han. Arglabin regulates microglia polarization to relieve neuroinflammation in Alzheimer's disease. Journal of biochemical and molecular toxicology. 2022 Jun;36(6):e23045