Polygalacic acid attenuates cognitive impairment by regulating inflammation through PPARγ/NF-κB signaling pathway.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101473265 Publication Model: Print Cited Medium: Internet ISSN: 1755-5949 (Electronic) Linking ISSN: 17555930 NLM ISO Abbreviation: CNS Neurosci Ther Subsets: MEDLINE

Original Publication: Oxford, UK : Wiley-Blackwell, c2008-

NF-kappa B*/metabolism ; Cognitive Dysfunction*/drug therapy ; Cognitive Dysfunction*/metabolism ; Saponins*; Oleanolic Acid/*analogs & derivatives; Mice ; Animals ; PPAR gamma ; Molecular Docking Simulation ; Signal Transduction ; Inflammation/metabolism ; Microglia

Aims: We aimed to explore the role and molecular mechanism of polygalacic acid (PA) extracted from traditional Chinese medicine Polygala tenuifolia in the treatment of Alzheimer's disease (AD).
Methods: The network pharmacology analysis was used to predict the potential targets and pathways of PA. Molecular docking was applied to analyze the combination between PA and core targets. Aβ42 oligomer-induced AD mice model and microglia were used to detect the effect of PA on the release of pro-inflammatory mediators and its further mechanism. In addition, a co-culture system of microglia and neuronal cells was constructed to assess the effect of PA on activating microglia-mediated neuronal apoptosis.
Results: We predict that PA might regulate inflammation by targeting PPARγ-mediated pathways by using network pharmacology. In vivo study, PA could attenuate cognitive deficits and inhibit the expression levels of inflammation-related factors. In vitro study, PA can also decrease the production of activated microglia-mediated inflammatory cytokines and reduce the apoptosis of N2a neuronal cells. PPARγ inhibitor GW9662 inversed the neuroprotective effect of PA. Both in vivo and in vitro studies showed PA might attenuate the inflammation through the PPARγ/NF-κB pathway.
Conclusions: PA is expected to provide a valuable candidate for new drug development for AD in the future.
(© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

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31627803 National Key Scientific Instrument and Equipment Development Projects of China; Beijing Scholars Program; Z201100005520017 Beijing Brain Initiative from Beijing Municipal Science and Technology Commission; Z201100005520016 Beijing Brain Initiative from Beijing Municipal Science and Technology Commission; 81530036 Key Project of the National Natural Science Foundation of China; U20A20354 Key Project of the National Natural Science Foundation of China

Keywords: Alzheimer's disease; Polygalacic acid; apoptosis; inflammation

0 (NF-kappa B)
0 (PPAR gamma)
22338-71-2 (polygalacic acid)
6SMK8R7TGJ (Oleanolic Acid)
0 (Saponins)

Date Created: 20240229 Date Completed: 20240301 Latest Revision: 20240418

20240419

PMC10851321

10.1111/cns.14581

38421141