ABSTRACT
PRIMARY OBJECTIVE: This study aimed to investigate the effects of low-, medium-, and high-dose puerarin on cognitive impairment induced by 50% alcohol in mice and revealed the role of autophagy-related signaling pathways (mTOR and JNK pathways) in this process. RESEARCH DESIGN: The alcohol-induced brain injury model was treated with different concentrations of puerarin. The cognitive function of mice was evaluated by the behavioral test, and the changes of target proteins in hippocampus of each experimental group were detected. METHODS AND PROCEDURES: 40 female Kunming mice were randomly divided into 5 groups. The cognitive ability of mice was tested by Morris water maze, the morphological changes in the CA1 area of hippocampus were observed by HE staining, and the target proteins in hippocampus were measured by WB and IHC. MAIN OUTCOMES AND RESULTS: Compared with the 50% alcohol group, the expression of p-mTOR/mTOR and p-4E-BP1/4E-BP1 in hippocampus was significantly decreased, while the expression of p-JNK/JNK, Beclin1, and LC3 was significantly increased in the medium- and high-dose puerarin groups. CONCLUSIONS: Puerarin could improve the cognitive impairment induced by 50% alcohol. The mTOR and JNK pathways related to autophagy might be involved in this process.
Subject(s)
Cognitive Dysfunction , Isoflavones , Animals , Autophagy , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Ethanol , Female , Hippocampus , Humans , Isoflavones/metabolism , Isoflavones/pharmacology , Isoflavones/therapeutic use , Male , Mice , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/pharmacologyABSTRACT
Glioblastoma multiforme (GBM) is one of the most frequent primary malignancies of the brain. Although the treatment strategy has significantly improved, patient prognosis remains poor. In vitro studies have shown that the right open reading frame kinase 1/protein kinase B (RIOK1-AKT) signaling pathway plays an important role in the malignant phenotype of glioma cells. This study aimed to investigate the co-expression of RIOK1 and ATK in glioma tissues and its clinical significance. Compared with normal tissues, RIOK1 and AKT1 expression were significantly upregulated in glioma tissues. In addition, patients with higher World Health Organization staging grades had increased RIOK1 and AKT1 expression levels, and RIOK1 and AKT1 expression were positively correlated. Notably, both RIOK1 and AKT1 expressions were correlated with poor prognosis. In vitro experiments showed that silencing RIOK1 inhibited the proliferation, migration, and invasion of glioma cell lines by suppressing AKT and c-Myc expression. These results indicate that the RIOK1-AKT1 axis could play an important role in GBM progression.
