Intracerebral hemorrhage (ICH) refers to a pathological condition characterized by the rupture of intracranial blood vessels triggered by an acute surge in blood pressure (An et al., 2017). It is categorized as a subtype of stroke (Balami and Buchan, 2012). ICH is characterized by significant morbidity and mortality and is recognized as a crucial clinical ailment with an exceptionally dire prognosis. The extravasation of blood following the rupture of a cerebral blood vessel can give rise to the mechanical compression of adjacent brain tissue. This compression subsequently induces an elevation in intracranial pressure and impairment of neurological functioning, thus categorizing it as a primary brain injury (Bautista et al., 2021).

Nevertheless, the efficacy of surgical eradication of ICH in patients seldom exhibits favorable neurological prognosis, frequently presenting potential hazards and unfavorable repercussions (de Oliveira Manoel, 2020; Dey et al., 2014). Conversely, secondary brain injury pertains to an array of pathological mechanisms activated by the byproducts of erythrocyte degradation, encompassing neuronal apoptosis, inflammatory reaction, oxidative stress, and impairment of the blood-brain barrier (BBB) (An et al., 2017; Manaenko et al., 2018; Tschoe et al., 2020; Xiao et al., 2020; Zhu et al., 2019).

Henceforth, it is imperative to emphasize the importance of formulating therapeutic interventions that specifically target anti-apoptotic and anti-inflammatory pathways, as they play a critical role in enhancing neurological outcomes after ICH. However, the existing arsenal of pharmacological agents with proven efficacy in facilitating neurological recovery post-ICH remains limited. Therefore, the need to explore and design a potent medicinal intervention for facilitating neurological recovery post-ICH assumes paramount significance. In recent times, substantial attention has been drawn towards Chinese herbal medicine and its intrinsic constituents as a potential treatment modality for ICH.

Leonurus japonicus Houtt. (the plant name has been checked with http://www.theplantlist.org), an herbaceous angiosperm, is a member of the Lamiaceae plant family and has its origins in China, Korea, India, and other Asian nations (Shang et al., 2014). In traditional medicine practices, Leonurus japonicus is commonly recognized for its diuretic, hypoglycemic, and antiepileptic properties (Wojtyniak et al., 2013). Furthermore, the contemporary processed Chinese herbal formulation, known as Leonurus injection, exhibits diverse therapeutic applications in the management of postpartum hemorrhage (Li, M.X. et al., 2022).

Leonurus japonicus, also known as Yi Mu Cao in TCM, derives its name from "herb beneficial to mother" in Chinese. Renowned for its remarkable efficacy and extensive usage spanning thousands of years in China, Leo is considered an exceptional traditional remedy (He et al., 2018; Yang et al., 2020). In China, Leo is predominantly employed for the treatment of gynecological ailments, while in European countries, it finds widespread application in neurological and cardiovascular disorders (Tahmouzi and Ghodsi, 2014).

Extensive research has identified over 200 biologically active constituents within Leo, primarily encompassing alkaloids, monoterpenes, sesquiterpenes, diterpenes, triterpenes, iridoids, flavonoids, sterols, phenylpropanes, and cyclic peptides (Wojtyniak et al., 2013; Zhang et al., 2018). Modern pharmacology has elucidated the various established biological activities associated with Leo, encompassing neuroprotection, anti-oxidation, anti-inflammation, analgesia, anti-apoptosis, anti-fibrosis, anti-infection, and anti-cancer properties, among others (Miao et al., 2019; Shang et al., 2014; Tahmouzi and Ghodsi, 2014; Wojtyniak et al., 2013; Zhang et al., 2018). The constituents and functional mechanisms underlying Leo's multifaceted effects are intricate and diverse.

Recent investigations have substantiated the neuroprotective capabilities of Leo in the context of cerebral ischemia-reperfusion injury (Li, Y. et al., 2021). Nonetheless, the synergistic potential of these active ingredients in facilitating therapeutic outcomes in the context of ICH and an all-inclusive rationale necessitate further investigation to be comprehensively understood.

Network pharmacology integrates bioinformatics, systems biology, and polypharmacy methodologies to investigate the intricate interplay between disease mechanisms and drug responses within the broader framework of biological networks, adopting a systems-oriented and holistic approach (Niu et al., 2021; Zhang, J. et al., 2019). The objective of network pharmacology research is to comprehensively address significant scientific inquiries across various dimensions systematically (Hopkins, 2008).

Within the realm of TCM, the notion of "multi-targets, multi-factors" aligns seamlessly with the holistic perspective of syndrome differentiation and treatment (Li, X. et al., 2022; Zhang et al., 2013; Zhang, R. et al., 2019). Chinese herbal medicine boasts a vast array of bioactive constituents, leading to diverse therapeutic targets and an extensive network of signaling pathways implicated in its therapeutic effects (Li, X. et al., 2022). The intricate nature of TCM necessitates comprehensive investigation, prompting a growing number of studies in the field to employ network pharmacology technology. This approach aims to provide fundamental and scientific elucidation for TCM-related inquiries (Fotis et al., 2018; Zhang, R. et al., 2019).

On the basis of Leontopodium's known biological functions, including neuroprotection, anti-inflammation, and anti-apoptosis, the present study employed a combined approach of network pharmacology and experimental verification to comprehensively investigate the principal active compounds and therapeutic targets of Leontopodium. Specifically, the oral bioavailability (OB) and drug-likeness (DL) aspects were considered (Wang and Lin, 2020). Subsequently, databases were queried to identify targets associated with ICH diseases. Leveraging this information, an intersection target network was established, encompassing both the disease-associated targets and the drug component targets. In addition, a protein-protein interaction (PPI) network involving the drug components and disease interaction targets was constructed, allowing the identification of core target genes associated with the efficacy of drug active compounds in treating ICH. To explore the signaling pathways linking the biological functions of Leontopodium to its therapeutic efficacy, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) analysis were performed. Subsequently, molecular docking technology was utilized to validate the binding interactions between the identified functional components and the main active compounds screened through the aforementioned analyses (Fig. 1). Finally, experimental investigations were conducted to verify the mechanism of action underlying the efficacy of Leontopodium's active compounds in the treatment of cerebral hemorrhage, offering a solid theoretical foundation for future research endeavors focused on the primary active compounds and molecular mechanisms of Leontopodium in addressing ICH.