Multimethodological and multiscale investigation of the therapeutic mechanism of Qian Ji Sheng Xue Pian in treating primary immune thrombocytopenia.

backgroundFor more than 30 years, Qian Ji Sheng Xue Pian (QJSXP) has been used clinically to treat primary immune thrombocytopenia (ITP) with good documented efficacy. However, nothing is known about its underlying mechanisms, effective components, and possible targets. To employ several methodologies to initially investigate the possible targets and therapeutic mechanisms of QJSXP in the treatment of ITP.

methodsLiquid chromatography-mass spectrometry (LC-MS) identified the principal chemical elements of QJSXP and assessed its probable active components based on ADME characteristics. The research incorporated multidimensional databases to pinpoint probable targets for the active components. Key pathogenic targets linked to ITP were aggregated from several illness databases, and the STRING and Metascape tools were utilized to examine protein interaction activities and related biological processes. Mendelian randomization (MR) was then utilized to determine beneficial targets for the therapy of ITP. The potential targets, including disease targets and MR-positive targets, were found at the intersection, while risk genes were excluded by heterogeneity, pleiotropy, and Steiger analysis to ascertain the core targets. Molecular docking and molecular dynamics simulations were conducted utilizing Schrodinger and Gromacs software to assess the binding affinity of compound-core targets. The toxicological effects of active molecules targeting critical sites were concurrently anticipated using several toxicity databases.

resultsA total of 67 active components and 352 potential targets were discovered in QJSXP, of which 77 were associated with ITP disease targets. Through MR analysis, a total of 12 core genes were identified. Binding scores below - 4.25 kcal/mol constituted 82.0%; docking scores below - 5 kcal/mol represented 60.1%, with an average binding energy of -5.44 kcal/mol. The majority of targets demonstrated strong binding affinity with the components. Toxicity prediction initially highlighted potential hazards, including hepatotoxicity and nephrotoxicity, establishing a foundation for future clinical surveillance.

conclusionThis study has preliminarily identified the active constituents, associated pathways, and possible targets of QJSXP in the treatment of ITP, offering insights for additional experimental validation of QJSXP's mechanism of action in ITP.