Network Pharmacology Reveals HSPA1A/BST2 as Potential Targets of Ci Bai Capsule's Active Compounds Intervening in Leukopenia

Abstract: Background: Radiation-induced leukopenia caused by low-dose exposure is frequently associated with Traditional Chinese Medicine (TCM) syndromes like "blood deficiency" and "fatigue syndrome". Ci Bai Capsule (CB) has been reported to enhance white blood cell levels; however, its mechanisms and bioactive compounds remain unclear.Aim: This study aimed to identify the bioactive compounds group of CB and elucidate its potential mechanisms in radiation-induced leukopenia.Methods: Syndrome-related data were gathered from SYMMAP and CTD database. CB's target profile is predicted by DrugCIPHER. Network pharmacology approaches were employed to identify active compounds and related pathways. Experimental validation was conducted through flow cytometry and RNA-sequencing in both ex vivo and in vivo models.Results: A total of 22 pathways related to cellular processes, immune responses, and signal transduction were identified. Five key bioactive compounds (kaempferol-3-glucorhamnoside, syringin, schisandrin, 3-hydroxytyrosol 3-O-glucoside and salidroside) were found to significantly modulate syndrome-related pathways. Optimal dosing of this compound combination enhanced leukocyte counts and splenic immune cell proliferation in irradiated mice. Transcriptomic analysis revealed that the compounds exert regulatory effects on PP1A, RB, CDK4/6, CDK2, and CDK1, thereby modulating downstream immune and hematopoietic markers such as MNDA, BST2, and HSPA1A.Conclusion: Our findings suggest that CB mitigates radiation-induced leukopenia by enhancing immune and hematopoietic recovery, offering a promising therapeutic approach for managing radiation-related hematological disorders.