Icarisid II rescues cognitive dysfunction via activation of Wnt/ß-catenin signaling pathway promoting hippocampal neurogenesis in APP/PS1 transgenic mice.
Phytother Res
; 36(5): 2095-2108, 2022 May.
Article
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| MEDLINE
| ID: mdl-35230733
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/ß-catenin signal pathway confirmed by upregulated Wnt-3a, phosphorylated glycogen synthase kinase-3ß (p-GSK-3ß), and ß-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/ß-catenin signaling pathway. In summary, our findings revealed that ICS II could improve neurogenesis and inhibit mitochondrial fission via activation of the Wnt/ß-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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Alzheimer
/
Disfunción Cognitiva
Límite:
Animals
Idioma:
En
Revista:
Phytother Res
Asunto de la revista:
TERAPIAS COMPLEMENTARES
Año:
2022
Tipo del documento:
Article
País de afiliación:
China