Research Paper Volume 16, Issue 10 pp 8657—8666
Gastrodin ameliorates neuroinflammation in Alzheimer’s disease mice by inhibiting NF-κB signaling activation via PPARγ stimulation
- 1 Department of Neurovascular Surgery, Bethune First Hospital, Jilin University, Changchun 130021, Jilin, China
- 2 Department of Neurovascular Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, China
- 3 Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021, Jilin, China
Received: January 5, 2024 Accepted: March 28, 2024 Published: May 15, 2024
https://doi.org/10.18632/aging.205831How to Cite
Copyright: © 2024 Yin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Aim: We investigated the effects and targets of gastrodin (GAS) for improving cognitive ability in Alzheimer’s disease (AD).
Methods: The targets and mechanisms of GAS were analyzed by network pharmacology. Morris water and eight-arm radial mazes were used to detect the behaviors of 7-months-old APP/PS1 mice. The levels of IBA-1 and PPARγ were examined by histochemical staining, nerve cells were detected by Nissl staining, inflammatory cytokines were measured by ELISA, and protein expressions were monitored by Western blotting. The neurobehavioral effects of GAS on mice were detected after siRNA silencing of PPARγ. Microglia were cultured in vitro and Aβ1-42 was used to simulate the pathology of AD. After treatment with GAS, the levels of inflammatory cytokines and proteins were assayed.
Results: Network pharmacological analysis revealed that PPARγ was the action target of GAS. By stimulating PPARγ, GAS inhibited NF-κB signaling activation and decreased neuroinflammation and microglial activation, thereby ameliorating the cognitive ability of AD mice. After silencing PPARγ, GAS could not further improve such cognitive ability. Cellular-level results demonstrated that GAS inhibited microglial injury, reduced tissue inflammation, and activated PPARγ.
Conclusions: GAS can regulate microglia-mediated inflammatory response by stimulating PPARγ and inhibiting NF-κB activation, representing a mechanism whereby it improves the cognitive behavior of AD.