ZSW

Zhengsui Wan (ZSW) is a commonly used traditional Chinese medicine formula for treating Acute Lymphatic Leukemia (ALL) in our institution, and it has shown potential efficacy. However, its mechanism of action (MoA) remains unclear. In this study, we systematically explored the ZSW in ALL (in vitro and in vivo) using network pharmacology and molecular docking techniques.

Mass spectrometry was conducted to analyze possible active components in ZSW. BALB/c mice were treated by ZSW aqueous decoction, and mesenchymal stem cells (MSCs) were extracted for proteomic analysis to evaluate differentially expressed proteins. Moreover, proteins associated with acute lymphoblastic leukemia in SwissTargetPrediction and GeneCards databases were screened, and they intersected with differentially expressed proteins to obtain potential targets for ZSW. Protein interactions were constructed for the selected targets. Then, we performed GO and KEGG enrichment analysis on its basis and screened the core target through K-core. We validated it by molecular docking with the top three actives in the molecular network in degree value. Finally, we detected the regulation of ICAM1 in MSCs by ZSW by qRT-PCR.

We detected 182 active ingredients in ZSW and identified 725 differential proteins in ZSWtreated mice, of which 25 were potential targets. Furthermore, MMP2, ICAM1, PSEN1, SLC9A1, and MMP14 were identified as core targets using the PPI network and K-core screening. Moreover, ZSW significantly downregulated ICAM1 expression in MSCs. GO and KEGG enrichment analyses showed that the results of ZSW were coordinated through immunomodulatory, inflammation-related, and drug resistance-related genes, including the PI3K-Akt, cAMP, and Wnt signaling pathways. Molecular docking and molecular dynamics simulations indicated moderate binding capacity between the active compounds and the screened target.

In this study, we successfully identified possible active ingredients and predicted potential targets and pathways for ZSW for the treatment of ALL. We provide a new strategy for further research on the molecular basis of ZSW biological effects in ALL. In addition, the potential active ingredients could provide new leads for drug discovery in ALL investigations.

Zangsiwei(ZSW) is a traditional Tibetan medicine from China consisting of extracts of Rhododendron anthopogonoides Maxim, Gentiana Tourn, Corydalis hendersonii Hemsl and Berberis kansuensis C.K.Schneid. Traditionally, ZSW has been used by Tibetan physicians to treat chronic respiratory diseases. The role of ZSW in particulate matter-induced lung inflammation and fibrosis remains unclear.

Combining non-targeted metabolomics, network pharmacology, and molecular docking to explore the mechanism of ZSW in the treatment of particulate matter-induced lung inflammation and fibrosis, and validated by in vivo and in vitro experiments.

The serum metabolite profile post-ZSW administration was first identified utilizing non-targeted metabolomics. Network pharmacology and molecular docking were employed to predict potential bioactive components and their corresponding targets. The in silico predictions were subsequently validated through in vivo studies in mice exposed to PM2.5 and silica dust, as well as in vitro studies utilizing human lung epithelial cells (A549) and lung fibroblasts (MRC5).

Metabolomic analysis identified specific serum metabolites that were associated with ZSW treatment. Network pharmacology and molecular docking identified key targets involved in the Transforming growth factor-β (TGF-β)/SMAD pathway, which were subsequently validated through in vivo experiments demonstrating a reduction in lung inflammation and fibrosis in ZSW-treated mice. In vitro studies demonstrated that ZSW exerts protective effects against PM2.5-induced cytotoxicity and modulates fibrotic markers in a dose-dependent manner. This is consistent with the inhibition of the TGF-β/SMAD pathway.

Our integrated approach, which combines non-targeted metabolomics, network pharmacology, and molecular docking, followed by rigorous in vivo and in vitro validation, establishes ZSW as a potential therapeutic agent for particulate matter-induced lung inflammation and fibrosis.