ABSTRACT
Hepatitis E is a disease of public health significance caused by the cross-species transmission of zoonotic hepatitis E virus (HEV) infection. There are no specific drugs. In this study, network pharmacology was used to reveal the mechanism of treatment of the active constituents of the Abrus cantoniensis Hance on hepatitis E. Based on the previously published representative components of A. cantoniensis Hance, we were screened the active components with OB ≥ 20% and DL ≥ 0.1 in A. cantoniensis Hance based on the TCMSP, predicted the target online through Swiss target prediction, and integrated the hepatitis E target in the GeneCards and DisGenet databases. Then, the core target was screened and the GO and KEGG enrichment and the network of the drug-active-ingredient-disease-pathway-target analysis were performed by the Cytoscape software. There were 11,046 hepatitis E targets, including PI3K-AKt, SRC, MAPK, PTPN11, EGFR, STAT1 and so on. The core ingredients include Oleanolic acid, Butin, ß-sitosterol, Soyasapogenol E, 5,7-dihydroxy-2-methyl-8-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one, Stigmasterol, Emodin, Physcion, and Enoxolone. A total of 1,410 GO enrichment results of core targets, including 1,246 biological process, 51 cell composition and 113 molecular function results. KEGG pathway was enriched in 150 related pathways, suggesting that A. cantoniensis Hance acts on cancer signaling pathway, endocrine resistance pathway, PI3K-AKt signaling pathway, MAPK, TNF and other signaling pathway. Through key components such as Oleanolic acid, Butin, ß-sitosterol, Stigmasterol, and Enoxolone and other components interferes with AKT1, IL-6 and TNF, and regulates pathway in cancer, PI3K-AKt signaling pathway and MAPK pathway to play a therapeutic role in hepatitis E.
ABSTRACT
The Chinese traditional medicinal plants Rheum palmatum L., Scutellaria baicalensis Georgi, and Houttuynia cordata Thunb in a ratio of 108:65:27 form a compound named Dahuang Qinyu San (DQS), which inhibits and kills Escherichia coli and Salmonella to a certain extent in fish and shrimp aquaculture environments. The active ingredients quercetin, emodin, baicalin, and aloe-emodin are obtained from the semi-biomimetic extract of DQS (SEDQS). However, the antibacterial mechanism of SEDQS against Salmonella is still unclear. This study used the microwell-plate method to determine the Minimum Inhibitory Concentration (MIC) of SEDQS against Salmonella enteritidis (S. enteritidis) isolated from geese. In addition, the effect of SEDQS on the growth curve, respiratory metabolic system, cell wall, soluble protein, and nucleic acid in bacterial liquid of S. enteritidis was detected by spectrophotometer and reagent kit. The effects of SEDQS on S. enteritidis DNA, binding gel blocking, virulence gene expression, and pathogenicity-related proteins were determined by gel electrophoresis, SDS-PAGE, and fluorescence quantitative PCR. The study found that a concentration of 1/4 MIC-2 MIC (2.27-18.2 mg/ml) SEDQS can significantly inhibit the normal growth of S. enteritidis, destroy the cell membrane structure of bacteria resulting in the leak of nucleic acid, protein, and other contents (P < 0.01). It also significantly inhibited the activities of succinate dehydrogenase (SDH) and malate dehydrogenase (MDH; P < 0.01) in a concentration-dependent manner. When the concentration of SEDQS was 1/2 MIC to 2 MIC (4.55-18.2 mg/ml), the expression levels of gyrB, fimA, filC, spvR, Hcp, and vgrG virulence genes (P < 0.01) all decreased by more than 31, 11, 18, 30, 34, and 21% respectively compared with the control group. SEDQS could significantly inhibit the expression of six virulence genes and play an important role in the pathogenicity of the S. enteritidis infected host. The SEDQS could exert antibacterial pharmacological effects by inhibiting the growth and metabolism of S. enteritidis and inhibiting the expression of major virulence factors. It has potential application value as an antibiotic alternative.
ABSTRACT
Staphylococcus aureus (S. aureus) biofilm plays an important role in the persistence of chronic infection due to its resistance to antibiotics. Because of their functional diversity, active polysaccharide is increasingly being applied as a biocontrol agent to inhibit the formation of biofilm by pathogens. In this study, a new polysaccharide, GBSPII-1, isolated from the fresh sarcotesta of Ginkgo biloba L. (G. biloba) was characterized and its effect on antibiofilm formation of S. aureus was examined in vitro. High-Performance Liquid Chromatography (HPLC) analysis showed that GBSPII-1 is an acidic heteropolysaccharide composed of mannose, rhamnose, glucose, glucuronic acid, and galacturonic acid. GBSPII-1 demonstrated a molecular weight of 34 kDa and may affect the accumulation of polysaccharide intercellular adhesion (PIA) by inhibiting icaA, icaB, icaC, and icaD gene expression at subinhibitory concentrations. Under 10 g/L, GBSPII-1 showed an antioxidant effect on the inhibition rate of H2O2-induced erythrocyte hemolysis and the scavenging rate of DPPH radicals was 76.5 ± 0.5% and 89.2 ± 0.26%, respectively. The findings obtained in this study indicate that GBSPII-1 has antibacterial effect, is a possible source of natural antioxidants, and may be a potential biocontrol agent for the design of new therapeutic strategies for biofilm-related S. aureus infections.
