ReferenceID 1894
Forsythoside A Mitigates Alzheimer's-like Pathology by Inhibiting Ferroptosis-mediated Neuroinflammation via Nrf2/GPX4 Axis Activation
Int J Biol Sci
Ferroptosis and neuroinflammation play crucial roles in Alzheimer's disease (AD) pathophysiology. Forsythoside A (FA), the main constituent of Forsythia suspensa (Thunb.) Vahl., possesses anti-inflammatory, antibacterial
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- Reference Id
- 1894
- Evidence Id
- 18484
- Core Evidence Id
- 18484
- Source Reference Id
- 3791
- Herb2 Reference Id
- HBREF004588
- Subject Paper Key
- HBIN026699_35342364
- Pubmed Id
- 35342364
- Doi
- 10.7150/ijbs.69714
- Paper Title
- Forsythoside A Mitigates Alzheimer's-like Pathology by Inhibiting Ferroptosis-mediated Neuroinflammation via Nrf2/GPX4 Axis Activation
- Paper Abstract
- Ferroptosis and neuroinflammation play crucial roles in Alzheimer's disease (AD) pathophysiology. Forsythoside A (FA), the main constituent of Forsythia suspensa (Thunb.) Vahl., possesses anti-inflammatory, antibacterial, antioxidant, and neuroprotective properties. The present study aimed to investigate the potential role of FA in AD neuropathology using male APP/PS1 double transgenic AD mice, Aβ 1-42 -exposed N2a cells, erastin-stimulated HT22 cells, and LPS-induced BV2 cells. FA treatment significantly improved mitochondrial function and inhibited lipid peroxidation in Aβ 1-42 -exposed N2a cells. In LPS-stimulated BV2 cells, FA treatment decreased the formation of the pro-inflammatory factors IL-6, IL-1β, and NO. In male APP/PS1 mice, FA treatment ameliorated memory and cognitive impairments and suppressed Aβ deposition and p-tau levels in the brain. Analyses using proteomics, immunohistochemistry, ELISA, and western blot revealed that FA treatment significantly augmented dopaminergic signaling, inhibited iron deposition and lipid peroxidation, prevented the activation of IKK/IκB/NF-κB signaling, reduced the secretion of pro-inflammatory factors, and promoted the production of anti-inflammatory factors in the brain. FA treatment exerted anti-ferroptosis and anti-neuroinflammatory effects in erastin-stimulated HT22 cells, and the Nrf2/GPX4 axis played a key role in these effects. Collectively, these results demonstrate the protective effects of FA and highlight its therapeutic potential as a drug component for AD treatment.
- Journal
- Int J Biol Sci
- Publish Year
- 2022
- Experiment Subject
- mouse; aβ 1-42 -exposed n2a cells; erastin-stimulated ht22 cells; lps-induced bv2 cells; lps-stimulated bv2 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Ferroptosis; Cognitive Impairments; Alzheimer's Disease
- Paper Title Cn
- Paper Title En
- Forsythoside A Mitigates Alzheimer's-like Pathology by Inhibiting Ferroptosis-mediated Neuroinflammation via Nrf2/GPX4 Axis Activation
- Bilingual Status
- semi_complete