Acute lung injury (ALI) is a common clinical condition that badly influences people’s health. Recent studies indicated that Aster tataricus (RA) had potential effects on ALI, but the effective components and their mechanism is not clear. In this study, we found that the Fraction-75 eluted from RA extract could significantly protect the lipopolysaccharide (LPS)-induced ALI in mice, including alleviating the severity of lung pathology, attenuating the pulmonary edema, and reducing the release of inflammatory cells. Further ingredient analyses demonstrated that there were mainly 16 components in it, among which 10 components were collected according to their relative peak area and oral bioavailability. Next, the components-disease targets network suggested that the candidate components had extensive associations with 49 known therapeutic targets of ALI, among which 31 targets could be regulated by more than one component. Herein, GO functional and pathway analysis revealed that the common targets were associated with four biological processes, including the inflammatory response to stimulus, cellular process, chemokine biosynthetic process and immune system process. Furthermore, the ELISA validation indicated that the candidate components in RA extract may protect the LPS-induced ALI mainly through inhibiting the release of inflammatory cytokines and promoting the repair of vascular endothelial.

Atherosclerosis (AS) is the leading cause of coronary heart disease, cerebral infarction, peripheral vascular disease, and other cardiovascular diseases, making it a major risk factor for high morbidity and mortality. Although long non-coding RNAs (lncRNAs) have been reported to play a role in AS, the specific effects of lncRNAs on AS remain largely unknown. Thus the purpose of this study was to explore the roles of mRNAs and lncRNAs in atherosclerosis via an ox-low-density lipoprotein induced macrophage-derived foam cell model. Microarray analysis identified a total of 50 688 mRNAs and 1514 lncRNAs, including 51 lncRNAs and 1730 mRNAs that were significantly dysregulated in the model group (p-adjust < 0.05 and |log 2FC| > 2). The results of gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that the dysregulated genes were associated with cell proliferation, cell apoptosis, and inflammatory responses. An lncRNA–mRNA co-expression network was created to further analyze the key regulatory genes. The lncRNAs Brip1os, Gm16586, AU020206, 9430034N14Rik, 2510016D11Rik, LNC_000709, Gm15472, Gm20703, and Dubr were identified as potential biomarkers in macrophage-derived foam cells. Based on 9 lncRNAs and 13 mRNAs, key genes influencing the degree of cell proliferation and cell apoptosis and the subsequent development of AS were identified. Q-PCR verified the key dysregulated genes. Thus, our results suggest potential therapeutic targets for AS and provide avenues for further research on AS pathogenesis.

The identification of network targets is one of the core issues used to reveal the molecular mechanism of traditional Chinese medicine (TCM) and is also the grand challenge of modernization of TCM. In this study, a protein–protein interaction (PPI) network was constructed based on the integration of network pharmacology and metabolomics, which was used as an effective approach to elucidate the relationship between disease pathway proteins and the targets of active small-molecule compounds. The intermolecular transfer process of the drug effect of active compounds in Salvia miltiorrhiza (SM) was revealed and visualized using the PPI network. Our study indicates that PTGS2 was the most important disease protein regulated by the active compounds in SM. Furthermore, the drug targets that can be linked to PTGS2 were regarded as direct targets and the direct targets of the active compounds were identified, respectively. Western blot and co-immuno precipitation (Co-IP) were used to verify the results of the network analysis and reveal the intermolecular transfer process of the effect of Tan IIA. Biological validation revealed that Tan IIA-EDN1-PTGS2-anandamide was a major intervention way of Tan IIA on early atherosclerosis (AS). This work provides a new perspective for the discovery of drug targets and the specific approaches regulated by the active compounds in SM on disease pathway proteins, which is beneficial for understanding the mechanism of action of bioactive compounds and expanding their clinical applications.