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.