Exploration of potential mechanism of Rougan formula against hepatic fibrosis by network analysis and experimental assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Rougan Formula (RG) has long been clinically applied to treat hepatic fibrosis in patients with different chronic liver diseases. However, the core active substances and the potential pharmacological mechanisms of RG remain unclear. AIM OF THE STUDY: The purpose of this study is to explore bioactive components, key targets, and potential mechanisms of RG by performing network pharmacological analyses and experimental model validation. MATERIALS AND METHODS: All chemical components in RG extract were identified using ultraperformance liquid chromatography-quadrupole/time-of-flight tandem mass technology. The candidate components and drug targets of RG, as well as disease-related genes, were extracted from TCMSP and GeneCards databases. The potential pathways related to genes were predicted by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The core bioactive components, key targets, and signaling pathways were ultimately obtained by analyzing protein-protein interaction (PPI) and component-target-pathway (C-T-P) networks. Subsequently, the efficacy and underlying mechanisms of RG on hepatic fibrosis were experimentally validated in transforming growth factor-beta 1 (TGF-ß1)-induced hepatic stellate cell activation model and CCL4-induced hepatic fibrosis mouse model. RESULTS: A total of 52 components in RG extract were obtained, and 22 of them were selected as the core bioactive components. Five hundred and thirty-nine overlapped targets were determined by matching drug targets with disease-related targets. The results of PPI and C-T-P network analyses revealed 100 key targets and 19 signaling pathways associated with RG efficacy. In vitro and in vivo studies further verified that RG exerted a significant anti-hepatic fibrotic effect by suppressing the activation of hepatic stellate cells by downregulating the TGF-ß1/Smads signaling pathway. CONCLUSIONS: These results may provide some evidence for further clinical research and development of RG formula as an effective and safe drug for hepatic fibrosis treatment.

An innovative method for manganese (Mn2+) and ammonia nitrogen (NH4+-N) stabilization/solidification in electrolytic manganese residue by basic burning raw material.

High concentrations of manganese (Mn2+) and ammonia nitrogen (NH4+-N) in electrolytic manganese residue (EMR) have seriously hindered the sustainable development of electrolytic manganese industry. In this study, an innovative basic burning raw material (BRM) was used to stabilize/solidify Mn2+ and NH4+-N in EMR. The characteristics of EMR and BRM, stabilize mechanism of NH4+-N and Mn2+, and leaching test were investigated. The concentrations of NH4+-N and Mn2+ were 12.8 mg/L and 0.1 mg/L, respectively, when the solid liquid ratio was 1.5:1, and the mass ratio of EMR and BRM was 100:10, at the temperature of 20 °C reacting for 12 h Mn2+ was mostly solidified as bustamite ((Mn,Ca)Si2O6), groutite (MnOOH) and ramsdellite (MnO2). NH4+-N was mostly recycled by (NH4)2SO4 and (NH4)3H(SO4)2. Leaching test results indicated that the concentrations of heavy metals were within the permitted level for the integrated wastewater discharge standard (GB8978-1996). Economic evaluation revealed that the cost of EMR treatment was $ 10.15/t by BRM. This study provided a new research idea for EMR harmless disposal.