Intracerebral hemorrhage (ICH) is a grave medical condition characterized by the occurrence of cerebral bleeding, often stemming from the rupture of blood vessels [1], [2]. This disruption of the blood supply can inflict tissue damage and impair neurological functions [3]. Guidelines for the management of Acute Stroke Management, clinical management to prevent increased intensity after bleeding, and consideration of surgical treatment in selected patients [4]. At present, there is no perfect treatment for ICH in clinical practice, and the initial treatment for ICH is antiplatelet therapy and blood pressure management to strictly manage high-risk factors for ICH [5], [6]. Other treatment strategies include seizure management, ICP management, surgical management, external ventricular drainage, intracranial pressure management, and thrombolytic evacuation [1], [7]. Angiogenesis, a biological process entailing the growth of new capillaries from an existing vascular network, is known to transpire during both developmental stages and adulthood [8]. Pertinently, prior investigations have substantiated the occurrence of angiogenesis subsequent to ICH [9], a phenomenon recognized for its pivotal role in the recovery of neurological functions [10], [11]. Research has established the Vascular Endothelial Growth Factor A (VEGFA) Signaling Pathway as a principal route governing angiogenesis [12], [13]. Within this pathway, VEGFR2 (KDR), SRC, AKT1, MAPK1, and MAPK14 emerge as critical proteins, collectively contributing to the regulation of angiogenic processes [14], [15].

One potential therapeutic strategy for enhancing post-ICH recovery involves the utilization of natural compounds with angiogenic properties [16], [17]. Traditional Chinese medicine (TCM), historically utilized for the treatment of stroke-related conditions, has demonstrated efficacy in managing ICH disorders [18]. Consequently, they are frequently employed in the clinical adjuvant treatment of ICH within traditional Chinese medicine [19], [20]. The concept of a “drug pair” pertains to the combination of two specific drugs in a unique manner within Chinese medicine clinical practice [21]. It represents the simplest and most fundamental form of multi-drug therapy, characterized by the mutual enhancement of therapeutic efficacy. Specifically, the combination of Panax notoginseng and Rhubarb has exhibited notable protective effects against ICH injury, attributed to its anti-apoptotic, antithrombotic, anti-inflammatory, and neuroprotective properties, and promotion of angiogenesis [22], [23]. Ginsenoside Rh2, derived from Panax ginseng, and Chrysophanol, derived from Rheum palmatum, have been the subjects of pharmacological investigations, revealing their respective attributes. Ginsenoside Rh2 has been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties [24], [25], while Chrysophanol has exhibited potential anti-inflammatory and neuroprotective effects in the context of ICH [26]. Literature also indicates that Panax ginseng and Rheum palmatum have the capacity to stimulate angiogenesis [27]. Ginsenoside Rh2 has been observed to exert neuroprotective effects via mechanisms involving anti-inflammatory and anti-apoptotic pathways [28], [29]. Furthermore, recent research has unveiled the neuroprotective potential of Chrysophanol [30]. However, the combined effects of Ginsenoside Rh2 and Chrysophanol in the context of ICH remain to be elucidated, warranting further investigation in comparison to their individual efficacy.

Network pharmacology, as an innovative approach, provides a novel avenue for investigating the synergistic mechanisms of traditional Chinese medicine [31]. It adeptly embodies the concept of holistic diagnosis and treatment, offering valuable insights into the compatibility mechanisms of herbal remedies. This approach facilitates the exploration of the “compound-proteins/genes-disease” pathway, allowing for the elucidation of intricate relationships among biological systems, drugs, and diseases from a network perspective. Consequently, the research methodology of network pharmacology finds application across diverse domains, including drug discovery, comprehension of pharmacological mechanisms, and the identification of novel therapeutic targets. Following topological analysis of drug-disease networks, molecular docking studies can further enhance the credibility of target prediction outcomes [32].

In the present study, to investigate the combined therapeutic impact and underlying mechanism of Ginsenoside Rh2 and Chrysophanol on intracerebral hemorrhage (ICH), we employed Network Pharmacology and molecular docking analysis to identify potential targets and pathways. Following this, we induced an experimental ICH model in male Sprague-Dawley (SD) rats by stereotactic injection of type VII collagenase into the right caudate putamen (CPu) to examine the effects of Ginsenoside Rh2 and Chrysophanol on angiogenesis post-ICH.