Icarisid II rescues cognitive dysfunction via activation of Wnt/β-catenin signaling pathway promoting hippocampal neurogenesis in APP/PS1 transgenic mice.

Abstract

Restoring the compromised neurogenesis has been served as a potential strategy to rescue cognitive dysfunction of Alzheimer's disease (AD). In this study, we explored whether icarisid II (ICS II), a natural product possessing powerful neuroprotection, could recover the neurogenesis dysfunction of APP/PS1 mice, and investigated its underlying mechanisms. Our results showed that oral administration of ICS II could alleviate cognitive injuries of APP/PS1 mice, promote hippocampal neurogenesis, as well as stimulate Wnt/β-catenin signal pathway confirmed by upregulated Wnt-3a, phosphorylated glycogen synthase kinase-3β (p-GSK-3β), and β-catenin. ICS II also depressed mitochondrial fission evidenced by upregulated Mitofusin 1 (Mfn 1) and Mitofusin 2 (Mfn 2), and downregulated mitochondrial fission 1 protein (Fis 1), mitochondrial fission factor (Mff), and phosphorylated dynamin-related protein 1 (p-Drp 1). However, these effects of ICS II were blunted by XAV-939, an inhibitor of Wnt/β-catenin signaling pathway. In summary, our findings revealed that ICS II could improve neurogenesis and inhibit mitochondrial fission via activation of the Wnt/β-catenin signaling pathway, which contributed to cognitive function restoration of APP/PS1 mice. This study discovered a novel mechanism involving neurogenesis regulation underlying the therapeutic effects of ICS II against AD.

• Authors: Hong-He Xiao, Ji-Cong Chen, He Li, Rui-Hai Li, Hai-Bo Wang, Hui-Peng Song, Hong-Yan Li, Guo-Shun Shan, Yu Tian, Yu-Meng Zhao, Jin-Ming Tian, Jing-Xian Yang
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 36 Issue 5 Pg. 2095-2108 (May 2022) ISSN: 1099-1573 [Electronic] England
• PMID: 35230733 (Publication Type: Journal Article)
• Copyright: © 2022 John Wiley & Sons Ltd.

Chemical References

• Amyloid beta-Protein Precursor
• Flavonoids
• Oligopeptides
• PS1 antigen
• beta Catenin
• baohuoside I
• Glycogen Synthase Kinase 3 beta

Topics

• Alzheimer Disease (drug therapy, metabolism)
• Amyloid beta-Protein Precursor (metabolism)
• Animals
• Cognitive Dysfunction (drug therapy)
• Flavonoids
• Glycogen Synthase Kinase 3 beta (metabolism)
• Hippocampus
• Mice
• Mice, Transgenic
• Neurogenesis
• Oligopeptides (metabolism)
• Wnt Signaling Pathway
• beta Catenin (metabolism)