Abstract Aim: Alzheimer’s disease (AD) is a neurodegenerative condition that is characterized by the gradual loss of memory and cognitive function. Icariin, which is a natural chemical isolated from Epimedii herba, has been shown to protect against AD. This research examined the potential mechanisms of Icariin’s treatment against AD via a comprehensive review of relevant preclinical studies coupled with network pharmacology. Methods: The PubMed, Web of Science, CNKI, WANFANG, and VIP databases were used to identify the relevant studies. The pharmacological characteristics of Icariin were determined using the SwissADME and TCMSP databases. The overlapping targets of Icariin and AD were then utilized to conduct disease oncology (DO) analysis to identify possible hub targets of Icariin in the treatment of AD. The hub targets were then used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and the interactions of the targets and Icariin were assessed via molecular docking and molecular dynamics simulation (MDS). Results: According to the literature review, Icariin alleviates cognitive impairment by regulating the expression of Aβ[1-42], Aβ[1-40], BACE1, tau, hyperphosphorylated tau, and inflammatory mediators. DO analysis revealed 35 AD-related hub targets, and the HIF-1 signalling pathway was ranked first according to the KEGG pathway analysis. Icariin effectively docked with the 35 hub targets and HIF-1α, and the dynamic binding of the HIF-1-Icariin complex within 100 ns indicated that Icariin contributed to the stability of HIF-1α. Conclusion: In conclusion, our research used a literature review and network pharmacology methods to identify the HIF-1 signalling pathway as a potential pathway for Icariin’s treatment against AD. Keywords: Icariin, Alzheimer’s disease, literature review, network pharmacology, HIF-1 signalling pathway 1 Introduction Alzheimer’s disease (AD) is a progressive neurological disorder that mostly affects elderly individuals and causes memory loss and other cognitive impairments ([32]Corbo et al., 2021). More than 50 million individuals throughout the globe are affected by this illness, which causes significant burden on current public health systems ([33]Opara et al., 2017). Amyloid-β (Aβ) plaques, neurofibrillary tangles (NFTs, composed of phosphorylated tau), and synaptic loss are recognized as the primary hallmarks of AD ([34]Breijyeh and Karaman, 2020; [35]Ashrafian et al., 2021), although the underlying aetiology is still not completely understood. Patients with this condition experience symptoms and dysfunction owing to neuronal loss, which is caused by different variables that have been implicated in the pathogenesis of AD. To date, AD is among the least well-served therapeutic areas for drug treatments. Employing agents that target the pathological mechanisms underlying this disease in order to delay its development is of great importance ([36]Cummings et al., 2019; [37]Breijyeh and Karaman, 2020). Icariin, which is a type of flavonoid, is the main ingredient that is extracted from Epimedium ([38]Jin et al., 2019). Multiple pharmacological activities, such as antioxidant, anti-inflammatory, and antiapoptotic activities, have been attributed to Icariin, which may account for the compound’s purported preventative and therapeutic efficacy in conditions as diverse as ischaemic stroke ([39]Liu et al., 2018; [40]Dai et al., 2021; [41]Wu et al., 2021), AD ([42]Ma et al., 2021; [43]Wang et al., 2022; [44]Yan et al., 2023), Parkinson’s disease ([45]Lu et al., 2018; [46]Zeng et al., 2019; [47]Khezri and Ghasemnejad-Berenji, 2022), multiple sclerosis ([48]Shen et al., 2015; [49]Cong et al., 2020), and depressive disorder ([50]Cao et al., 2019; [51]Xu et al., 2020; [52]Zeng et al., 2022). Several studies have demonstrated that Icariin treatment can suppress Aβ production to improve learning and memory in animals ([53]Jin et al., 2014a; [54]Chen et al., 2016a; [55]Chuang et al., 2021). However, the pharmacological properties of Icariin and the molecular basis for its effects on AD are not fully understood. Network pharmacology is a systematic and comprehensive research strategy that is used to predict the mechanisms by which drug treatments affect illnesses, and it involves a “network-target, multiple-component-therapeutics” approach ([56]Zhang et al., 2019a). Molecular docking is used to predict the binding mode and affinity of receptors and the mode of interaction between receptors and drug moleculars ([57]Pinzi and Rastelli, 2019). By combining drug target networks with biological system networks, network pharmacology facilitates novel approaches to drug discovery. However, network pharmacology has not been used to explore the neuroprotective role of Icariin in AD. In the current study, a literature review combined with network pharmacology was used to systemically analyse the neuroprotective role of Icariin in AD and to comprehensively predict the possible mechanisms. The flow chart of this study was shown in [58]Supplementary Material S1. 2 Material and methods 2.1 The meta-analysis This study conducted a comprehensive literature search to identify appropriate studies that described improved learning and memory functions in rodent animal AD models after Icariin treatment. We collected the relevant literature from five separate databases, namely, PubMed, Web of Science, CNKI database, Wanfang database, and VIP database, and the published languages were either English or Chinese. The period for the literature review was from the establishment of the database to August 2022. The strategies for article retrieval are shown in [59]Supplementary Material S2. The quality of each study was independently evaluated by two researchers. 2.1.1 Inclusion and exclusion criteria 2.1.1.1 Inclusion criteria * 1) AD rodent animal models regardless of the species, age, sex, or weight of the animals. * 2) The experimental group was treated with Icariin. A control group treated with a placebo, such as saline or similar vehicles, was also needed. The doses, administration methods, and duration of treatment were not limited. * 3) The study was an original experimental study of the effects of Icariin on animal models of AD. 2.1.1.2 Exclusion criteria * 1) Literature containing incorrect or missing information; duplicate references; review articles; absence of complete text.