Network pharmacology combined with metabolomics to reveal the anti-fibrotic mechanism of Polygoni Orientalis Fructus in CCl4-induced hepatic fibrosis rats.

Polygoni Orientalis Fructus (POF), a dried ripe fruit of Polygonum orientale L., is commonly used in China for liver disease treatment. However, its therapeutic mechanism remains unclear. The aim of this study was to elucidate the effects of POF on the regulation of endogenous metabolites and identify its key therapeutic targets in hepatic fibrosis (HF) rats by integrating network pharmacology and metabolomics approaches. First, serum liver indices and histopathological analyses were used to evaluate the therapeutic effects of POF on carbon tetrachloride (CCl4)-induced HF. Subsequently, differential metabolites and potential therapeutic targets of POF were screened using plasma metabolomics and network pharmacology, respectively. The key targets of POF were identified by overlapping differential metabolite-associated targets with the potential targets and validated by molecular docking and ELISA experiments. The results showed that POF effectively alleviated HF in rats. A total of 51 metabolites related to HF were screened, and 24 were associated with POF. 232 potential therapeutic targets were identified by network pharmacology analysis. Finally, six key targets were identified through a combined analysis. Furthermore, molecular docking and ELISA validation revealed that AGXT, PAH, and NOS3 are targets of POF action, while CBS, ALDH2, and ARG1 were identified as potential targets. SIGNIFICANCE: POF is now commonly used in the treatment of liver disease, but its mechanism of action remains unclear. Current studies on metabolomics of liver disease primarily focuse on the interpretation of differential metabolites and related metabolic pathways. This research delves into the intricate details of metabolomics findings via network pharmacology to uncover the targets and pathways of drug action.

Cellular metabolomics study of the antitumor mechanism of Sijunzi decoction combined with mitomycin C.

Mitomycin C (MMC) has an antitumor effect and is considered as a broad-spectrum antibiotic. Sijunzi Decoction (SJZD), a well-known ancient Chinese prescription, is widely used in the treatment of cancer when combined with chemotherapy drugs. Studies have shown that SJZD can be combined with other drugs to enhance the therapeutic effect against cancer and inhibit the toxicity of chemotherapy drugs, but the specific mechanism is not clear. Thus, we hope to further explore the antitumor mechanism of combined SJZD and MMC. 3-(4,5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry, western blot, 1H NMR and HPLC-MS were used to study the mechanism at the cellular level. The results show that the combined administration can have a more significant effect on inhibiting the proliferation of cancer cells, promoting their apoptosis. Based on metabolomics, 38 biomarkers were found in the MMC group and 43 biomarkers were found in the combined administration group. Among them, 18 unique biomarkers were discovered in the combined administration group. Studies have shown that the antitumor mechanism of combined administration is related to amino acid metabolism, energy metabolism, lipid metabolism and nucleotide metabolism, among which amino acid metabolism is the most important. In addition, SJZD achieves the effect of toxin reduction and efficiency enhancement by improving the body's immunity and improving the oxidative stress environment.