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Abstract
Context
Qinggong Shoutao Wan (QGSTW) is a pill used as a traditional medicine to treat age-associated memory decline (AAMI). However, its potential mechanisms are unclear.
Objective
This study elucidates the possible mechanisms of QGSTW in treating AAMI.
Materials and methods
Network pharmacology and molecular docking approaches were utilized to identify the potential pathway by which QGSTW alleviates AAMI. C57BL/6J mice were divided randomly into control, model, and QGSTW groups. A mouse model of AAMI was established by d-galactose, and the pathways that QGSTW acts on to ameliorate AAMI were determined by ELISA, immunofluorescence staining and Western blotting after treatment with d-gal (100 mg/kg) and QGSTW (20 mL/kg) for 12 weeks.
Results
Network pharmacology demonstrated that the targets of the active components were significantly enriched in the cAMP signaling pathway. AKT1, FOS, GRIN2B, and GRIN1 were the core target proteins. QGSTW treatment increased the discrimination index from −16.92 ± 7.06 to 23.88 ± 15.94% in the novel location test and from −19.54 ± 5.71 to 17.55 ± 6.73% in the novel object recognition test. ELISA showed that QGSTW could increase the levels of cAMP. Western blot analysis revealed that QGSTW could upregulate the expression of PKA, CREB, c-Fos, GluN1, GluA1, CaMKII-α, and SYN. Immunostaining revealed that the expression of SYN was decreased in the CA1 and DG.
Discussion and conclusions
This study not only provides new insights into the mechanism of QGSTW in the treatment of AAMI but also provides important information and new research ideas for the discovery of traditional Chinese medicine compounds that can treat AAMI.
Author contributions
Guiyun Pan and Lijuan Chai are co-first authors. Yingqiang Zhao and Yi Wang were involved in the study design and coordination, provided material support, obtained funding, and supervised the study. Guiyun Pan, Zhihui Song and Wanying Feng performed the network analysis. Lijuan Chai, Rui Chen and Qing Yuan designed the validation experiment. Jinna Wei, Zhihua Yang, Yuhang Zhang and Guinan Xie performed the experiments. Guiyun Pan and Lijuan Chai wrote and revised the manuscript. An Yan, Qingbo Lv and Caijun Wang performed most of the experiments and statistical analyses. All authors approved the final version of the paper.
Disclosure statement
No potential conflict of interest was reported by the author(s).