BACKGROUND:The processes of mechanical ventilation-induced lung injury (VILI) triggers the release of high-mobility group box 1 (HMGB1), a prominent damage-associated molecular pattern (DAMP) family member, which can cause damage to pulmonary vascula...

Tanshinones are a class of abietane diterpene compounds extracted from Salvia miltiorrhiza, and have been used for medical purposes in traditional Chinese medicinal practices. This herb has been used in the treatment of chronic obstructive pulmonary disease (COPD), breast cancer and inflammatory disorders. This study examined the anti‑inflammatory properties of tanshinones. In addition, lipid‑soluble compounds which were specific to Tanshinone class were also highlighted, out of which two compounds, dihydrotanshinone I and cryptotanshinone were selected with the aim of creating a new research perspective in order to further elucidate the mechanisms of the pathogenesis of inflammatory diseases. Moreover, interaction analyses were carried out successfully to determine the interactions formed between both dihdrotanshinone I and cryptotanshinone, and target proteins. The bioactivity properties and various other pharmacokinetic and pharmacodynamic analyses discerned that crytptotanshinone was more effective dihydrotanshinone and more ‘drug‑like’ than its counterpart. It was found to have a better solubility and permeability, and thus has potential for use as an anti‑inflammatory agent.

Context: AMD3100, a CXCR4 antagonist, has beneficial effects immaculate in the treatment of acute lung injury (ALI). Objective: ALI is a severe inflammatory condition associated with poor prognosis and limited treatment options. AMD3100, has therapeutic effects that reduce ALI. Our study explored the regulatory mechanisms of AMD3100 in alleviating the injury of lipopolysaccharide (LPS)-induced ALI in mice. Materials and Methods: Male ICR mice were randomly divided into control, LPS-treated, AMD3100-treated, and LPS + AMD3100-treatment groups. The histological changes of lung tissues from different groups were evaluated using hematoxylin and eosin staining. Lung injury was measured by ELISA and lung wet/dry ratio. Moreover, lung tissues from the four groups were subjected to transcriptome sequencing followed by differential expression, functional enrichment, protein-protein interaction (PPI) networks, and transcription factor analyses. The validation of mRNAs and protein levels were conducted with qRT-PCR and ELISA. Results: Hematoxylin and eosin staining combined with the concentration of IL-1 and IL1-β and lung wet/dry ratios revealed that AMD3100 reduced the level of LPS-induced lung injury. Analysis of the transcriptome sequencing data identified 294 differentially expressed genes in the LPS-induced ALI mouse model. Based on the PPI network and module analysis, hub targets of AMD3100, such as Cxcl10 and Cxcl9, were identified in module 1, and hub targets, such as Cxcl12 and Cxcl1, were identified in module 2. Cxcl10 and Cxcl9 are involved in the Toll-like receptor signaling pathway, and Cxcl12 and Cxcl1 arae enriched in the nuclear factor-kappa B signaling pathway. Cxcl19, Cxcl10, and Cxcl1 are targeted by transcription factors like NF-κB. The validation of mRNAs and protein levels conducted by PCR and ELISA supported our transcriptome data. Conclusions: Our findings indicate that AMD3100 may exhibit a therapeutic effect on LPS-induced ALI in mice by modulating multiple chemokines to inhibit the Toll-like receptor/nuclear factor-kappa B signaling pathway.