Analysis of ligustrazine covalent cyclodextrin frameworks in bioinformatics and network pharmacology-based acute lung injury treatment

Acute lung injury (ALI) is a grave and potentially fatal acute inflammatory condition. Ligustrazine (LIG), an active ingredient in traditional Chinese medicine (TCM), has been proven to inhibit ALI oxidative stress and inflammatory responses; however, its mechanism of ALI treatment remains unclear. We investigated the molecular mechanism of LIG covalent cyclodextrin backbone (LIG-OC-COF) granules in ALI treatment. Network pharmacology identified 16 potential LIG targets, including BCL2L1, JAK2, CDK2, HIF1A , and CCNA2 . The Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis suggested that these points were involved in the Janus kinase/signal transducer and activator of transcription (JAK/STATs) signaling pathway. The results from the molecular docking further confirmed the stable binding affinity between target proteins and LIG. In vivo experiments revealed that LIG downregulated the expression of pro-inflammatory factors (i.e., Tumor Necrosis Factor-α (TNF-α), Interleukin - 1β (IL-1β), and Interleukin - 6 (IL-6); P < 0.0001) and upregulated the expression of the anti-inflammatory factor (i.e., IL-10; P < 0.0001) in the serum of ALI rat models. This effectively alleviated the apoptosis of ALI lung cells ( P < 0.0001) and downregulated the mRNA expression of the aforementioned key targets ( P < 0.0001) and the related proteins in the JAK2/STAT3 signaling pathway ( P < 0.0001). The inhalation of LIG - covalent cyclodextrin frameworks (LIG-OC-COF) may exert its therapeutic effect by modulating the expression of key target molecules. LIG exhibits an anti-inflammatory and anti-apoptotic effect on lung tissues by regulating the BCL2L1, JAK2, CDK2, HIF1A , and CCNA2 molecules and affecting the activation of the JAK/STAT signaling pathway. LIG-OC-COF can enhance these changes. LIG-OC-COF) granules targeting lung delivery of LIG is an effective ALI treatment.