Mechanism of Shiliu Buxue Syrup for anemia using integrated metabolomics and network pharmacology.

For many years, Shiliu Buxue Syrup (SLBXS) has been used in the treatment of anemia in Xinjiang, China. However, the potential therapeutic mechanism of SLBXS in the treatment of anemia remains unclear. We qualitatively analyzed the ingredients of SLBXS and predicted the underlying mechanisms by network pharmacology. A mice model of anemia was established by subcutaneous injection of 1-Acetyl-2-phenylhydrazine (APH). Spleen metabolomics was performed to screen potential biomarkers and pathways related to anemia. Furthermore, core targets of crucial pathways were experimentally validated. Finally, molecular docking was used for predicting interactions between compositions and targets. Network pharmacology indicated that the 230 SLBXS ingredients may affect 141 target proteins to regulate the PI3K/AKT and HIF-1 signaling pathways. Metabolomics revealed that SLBXS could mediate 30 biomarkers, such as phosphoric acid, l-pyroglutamic acid, alpha-Tocopherol, 1-stearoyl-rac-glycerol, and dihydroxyacetone phosphate, to regulate drug metabolism-other enzymes, glutathione metabolism, glycolysis or gluconeogenesis, nicotinate and nicotinamide metabolism, nitrogen metabolism, and purine metabolism. Western blot indicated that SLBXS can regulate the protein expression levels of AKT1, Bcl2, Caspase3, HIF-1α, VEGF-A, and NOS2. The molecular docking revealed that most of the compositions had a good binding ability to the core targets. Based on these findings, we speculate that SLBXS treats anemia mainly by modulating the PI3K/AKT and HIF-1 pathways and glutathione and glycolytic metabolisms.

Integrative transcriptomics and metabolomics analyses provide hepatotoxicity mechanisms of asarum.

Asarum is frequently applied in combination with other agents for prescriptions in practices of Traditional Chinese Medicine. A number of studies have previously indicated that asarum treatment induces lung toxicity by triggering inflammation. However, the potential effects of asarum in the liver and the underlying mechanisms have remained largely elusive. Therefore, transcriptomics and metabolomics approaches were used in the present study to examine the mechanisms of the hepatotoxicity of asarum. Specifically, mRNA and metabolites were obtained from rat liver samples following intragastric administration of asarum powder. RNA sequencing analysis was subsequently performed to screen for differentially expressed genes (DEGs), and a total of 434 DEGs were identified in liver tissue samples, 214 of which were upregulated and 220 were downregulated. Pathway enrichment analysis found that these genes were particularly enriched in processes including the regulation of p53 signaling, metabolic pathways and bile secretion. To investigate potential changes to the metabolic profile as a result of asarum treatment, a metabolomics analysis was performed, which detected 14 significantly altered metabolites in rat liver samples by gas chromatography-mass spectrometry. These metabolites were predominantly members of the taurine, hypotaurine and amino acid metabolic pathways. Metscape network analyses were subsequently performed to integrate the transcriptomics and metabolomics data. Integrative analyis revealed that the DEGs and metabolites were primarily associated with bile acid biosynthesis, amino acid metabolism and the p53 signaling pathway. Taken together, these results provide novel insight into the mechanism of asarum-mediated hepatotoxicity, which may potentially aid the clinical diagnosis and future therapeutic intervention of asarum poisoning.

The analgesic and anti-inflammatory effects of zukamu granules, a traditional Chinese medical formulation.

Context: Zukamu granule, a traditional Chinese medicine, has shown clinical treatment efficacy. However, the pharmacodynamic effects and possible anti-inflammatory mechanisms of zukamu are still unclear.Objective: To investigate the analgesic and anti-inflammatory effects and possible mechanisms of zukamu granules on acute lung injury.Materials and methods: Kunming mice and Sprague Dawley rats were gavaged with zukamu (1.35, 2.7 and 5.4 g/kg, respectively) or ganmaoling (GMLG; 2.7 g/kg) once a day for 7 d. Dexamethasone treatment (5 mg/kg) were administered only on the last day. Analgesic effects were evaluated through the hot plate test and acetic acid writhing test. The expression of cytokines and proteins was measured in serum and lung tissues to elucidate the efficacy of zukamu against lung injury.Results: Significant analgesic effects were observed at 30 min after zukamu administration at medium and high doses (p < 0.05), but the effect was not obvious at low dose until 60 min post-administration (p > 0.05). Zukamu treatment at all doses notably reduced the lung wet-to-dry (W/D) ratios compared to that of model rats (p < 0.05) and the effect was more evident at high dose compared to those at medium and low doses. The levels of cytokines and proteins in the lung tissues were inhibited by zukamu.Conclusions: Zukamu exhibited analgesic and protective effects against lung injury via regulating NF-κB signalling and inflammatory cytokines. As zukamu granules contain multiple ingredients, further exploration of the mechanisms underlying its analgesic and anti-inflammatory functions were needed.