Nasopharyngeal carcinoma (NPC) is a malignant neoplasm intimately associated with particular geographic locations and characterized by a multifaceted etiology (Liu et al., 2023). Given the distinct anatomical location of NPC, achieving complete surgical excision proves immensely challenging. Additionally, its inconspicuous symptoms contribute to the diagnosis of 70% of patients at an advanced stage (Cheng et al., 2022). This is despite significant advances in treatment and diagnosis in recent years, its high incidence, insidious course, and easy metastasis make NPC still challenging to diagnose. Chemotherapy is an important tool in the treatment of NPC, but chemoresistance and serious adverse effects limit its application (Guan et al., 2020). Therefore, it is particularly important to find novel anti-NPC drugs with high efficiency and low toxicity and to reduce the side effects in patients. Network pharmacology transcends the conventional “one drug, one gene, one disease” research paradigm, embracing a novel investigative approach that delves comprehensively into the mechanisms of drug therapy for diseases through the exploration of multiple components, targets, and pathways (Guo et al., 2021; Wu et al., 2022). Natural products have wielded pivotal roles in medicine, and the application of network pharmacology methodologies to unveil their multi-target, multi-pathway mechanisms has found widespread utility within the realm of drug development (Li et al., 2022; Noor et al., 2022).

Stephania cephalantha Hayata (http://www.theplantlist.org/, accessed on September 5, 2023) is an important traditional medicinal plant (M et al., 2022). Stephania cephalantha Hayata holds extensive therapeutic value, finding particular prominence in traditional medicine across several Asian nations for the treatment of conditions such as asthma, dysentery, cancer, and inflammation (C et al., 2014; DK et al., 2010). Copious research underscores the anticancer activity of extracts and alkaloids from Stephania cephalantha Hayata (De Xu et al., 2015; Shang et al., 2021). Alkaloids stand as the primary bioactive constituents within the genus Stephania plant, with Cepharanthine (CEP, Fig. 2A) standing out as both the most abundant and multifariously pharmacologically active representative compound (M et al., 2022; Y et al., 2023). CEP emerges as a natural compound possessing a myriad of pharmacological activities, encompassing immune modulation, antitumor, and antiviral effects (Bailly, 2019). In recent years, researchers have been focusing on the potential application of CEP in the realm of antitumor therapy, which has attracted attention for its various mechanisms of action, encompassing the inhibition of proliferation, induction of apoptosis, and modulation of the immune response (Feng et al., 2021; J et al., 2017). These attributes position CEP as a promising candidate for anticancer drug development. Nevertheless, while CEP displays potential in the field of anticancer treatment, its efficacy in the context of NPC remains incompletely explored. The objective of this research is to investigate the probable impacts of CEP as a cancer-fighting substance against NPC and reveal the underlying mechanisms behind its actions. The methodology for this study is depicted in Fig. 1, where a combination of network pharmacology and experimental verification was employed through both in vivo and in vitro trials to comprehensively examine the potential targets and workings of CEP in combating NPC.