Alzheimer’s disease (AD) is presently the most prevalent neurodegenerative disorder leading to dementia in the elderly population (Mucke, 2009). The primary clinical manifestation of AD is cognitive impairment, accompanied by functional decline. Two distinctive pathological features of AD include the accumulation of amyloid beta peptide (Aβ) in the cerebral cortex and hippocampus, forming neurogenic plaques, as well as the formation of neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein. These pathological changes disrupt microtubule function, impair axonal transport, and result in synaptic and neuronal damage. Ultimately, these protein abnormalities lead to the loss of neuronal connections, culminating in neuronal death and brain tissue loss (Talamo et al., 1989). Current therapeutic approaches for delaying AD primarily involve drug therapy, immunotherapy, and gene engineering technology. However, these strategies are not comprehensive, and their application is limited due to adverse effects on liver and kidney function, as well as the occurrence of complications (Reardon, 2023; Selkoe, 1999). Consequently, the identification of novel drugs with high efficacy and minimal toxic side effects remains a challenging and rewarding pursuit (Shen, 2013). To address these limitations, researchers worldwide have increasingly focused on investigating the potential of Traditional Chinese Medicine (TCM) interventions in the treatment of AD.

TCM has long been recognized for its efficacy and potential in treating AD due to its notable therapeutic effects and minimal side effects (Fernandes et al., 2022). In the ancient TCM text “Bianzhenglu · Daibingmen,” AD, Vascular dementia and other cognitive disorders are collectively referred to as “Dementia”, which is attributed to deficiencies in kidney essence and qi and blood, resulting from the accumulation of phlegm and blood stasis, as well as liver depression and stomach deficiency (Xie and Xie, 2020). Consequently, treatment strategies should focus on resolving stagnation, expelling phlegm, and strengthening stomach ventilation, in addition to syndrome differentiation and treatment (Chen, 2006; Li et al., 2024). Guhan Yangshengjing (GHYSJ) is a TCM prescription developed based on the medical classics unearthed from the Mawangdui Han tomb. The composition of the prescription comprises eleven herbs, namely Panax Ginseng C. A. Mey., Astragali Radix, Epimedii Folium, Polygonati Rhizoma, Lycii Fructus, Rosa laevigatae Fructus, Cuscutae Semen., Ligustri lucidi Fructus., Paeoniae Radix Alba, Glycyrrhizae Radix et Rhizoma, Hordei Fructus Germinatus (Zhang et al., 2021). This formula is reputed for its potential for totonifying qi and blood, strengthening the stomach and spleen and soothing the liver to relieve depression. GHYSJ has been widely use in clinical practice for the treatment of various conditions, including cognitive disorder, senile cerebral atrophy and depression (Liu, 1995; Yu, 1995; Yu et al., 2014). It has been recognized in the clinical treatment of elderly diseases and listed as a proprietary Chinese medicine. Notably, GHYSJ and its constituent have exhibited noteworthy efficacy in mitigating inflammation and modulating hippocampal synaptic protein activity (Deng, 2020; Hou, 2019). However, the precise pharmacological mechanisms through which GHYSJ exerts its regulatory effects on AD remain elusive, thereby impeding its widespread adoption in clinical practice.

The efficacy of TCM is well-established, although challenges persist in understanding its complex composition and elucidating its mechanisms of action (Ai et al., 2022; Cheung et al., 2022; Muhammad et al., 2021; Wu et al., 2024). In recent years, the integration of network pharmacology with systems biology and computational approaches has emerged as a promising strategy (Huang et al., 2019; Zhao et al., 2023). By constructing “drug composition - gene - disease” interaction networks and identifying key signaling nodes, this approach enables the elucidation of the intervention mechanisms of multi-molecular drugs on disease networks (Fang et al., 2017). Consequently, it has found widespread application in the study of TCM compounds, which are characterized by their multi-components, multi-targets, and multi-pathways nature (Bai et al., 2023; Huang et al., 2023; Huo et al., 2022). However, it is important to note that the accuracy of TCM target prediction through network pharmacology is not entirely reliable, as it heavily relies on existing literature and databases (Li et al., 2022, 2023). Therefore, to ensure the validity of the results, it is crucial to complement network pharmacology with molecular docking and experimental validation.

In this study, our objective was to elucidate the underlying mechanism by which GHYSJ exerts its therapeutic effects in AD. To achieve this, we employed network pharmacology to predict the potential targets and signaling pathways associated with GHYSJ in the treatment of AD. Additionally, we conducted molecular docking and molecular force analyses to investigate the interrelationship between the core components and core targets of GHYSJ. At the same time, we detected the chemical constituents by LC-MS and HPLC to analyzed the results from TCMSP database. Previous research has demonstrated that Aβ can induce cytotoxicity and apoptosis (Jiang et al., 2022). Therefore, we further validated the findings obtained through network pharmacology by establishing an Aβ-stimulated SH-SY5Y cellular model, allowing us to elucidate the potential targets and pathways through which GHYSJ may exert its therapeutic effects in AD.