Proteomics and network pharmacology of Ganshu Nuodan capsules in the prevention of alcoholic liver disease.

Introduction: Ganshu Nuodan is a liver-protecting dietary supplement composed of Ganoderma lucidum (G. lucidum) spore powder, Pueraria montana (Lour.) Merr. (P. montana), Salvia miltiorrhiza Bunge (S. miltiorrhiza) and Astragalus membranaceus (Fisch.) Bunge. (A. membranaceus). However, its pharmacodynamic material basis and mechanism of action remain unknown. Methods: A mouse model of acute alcohol liver disease (ALD) induced by intragastric administration of 50% alcohol was used to evaluate the hepatoprotective effect of Ganshu Nuodan. The chemical constituents of Ganshu Nuodan were comprehensively identified by UPLC-QTOF/MS, and then its pharmacodynamic material basis and potential mechanism of action were explored by proteomics and network pharmacology. Results: Ganshu Nuodan could ameliorate acute ALD, which is mainly manifested in the significant reduction of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and malondialdehyde (MDA) content in liver and the remarkably increase of glutathione (GSH) content and superoxide dismutase (SOD) activity in liver. Totally 76 chemical constituents were identified from Ganshu Nuodan by UPLC-QTOF/MS, including 21 quinones, 18 flavonoids, 11 organic acids, 7 terpenoids, 5 ketones, 4 sterols, 3 coumarins and 7 others. Three key signaling pathways were identified via proteomics studies, namely Arachidonic acid metabolism, Retinol metabolism, and HIF-1 signaling pathway respectively. Combined with network pharmacology and molecular docking, six key targets were subsequently obtained, including Ephx2, Lta4h, Map2k1, Stat3, Mtor and Dgat1. Finally, these six key targets and their related components were verified by molecular docking, which could explain the material basis of the hepatoprotective effect of Ganshu Nuodan. Conclusion: Ganshu Nuodan can protect acute alcohol-induced liver injury in mice by inhibiting oxidative stress, lipid accumulation and apoptosis. Our study provides a scientific basis for the hepatoprotective effect of Ganshu Nuodan in acute ALD mice and supports its traditional application.

Study of Xuanhuang Pill in protecting against alcohol liver disease using ultra-performance liquid chromatography/time-of-flight mass spectrometry and network pharmacology.

Introduction: Xuanhuang Pill (XHP) is a traditional Chinese medicine oral formula composed of 10 herbs. This study aims to verify the hepatoprotective activity of XHP and explain its possible mechanism. Methods: The hepatoprotective activity of XHP was evaluated by constructing a mouse model of alcoholic liver disease, and the mechanism of XHP was preliminarily explained by utilizing ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-QTOF/MS), proteomics and network pharmacology. Results: The current study demonstrated that treatment with XHP ameliorated acute alcohol-induced liver injury in mice by significantly reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and triglycerides (TGs) and malondialdehyde (MDA) content. Remarkably, treatment also increased superoxide dismutase (SOD) activity and glutathione (GSH) content. UPLC-QTOF/MS, 199 compounds were identified as within the make-up of the XHP. Network pharmacology analysis showed that 103 targets regulated by 163 chemical components may play an important role in the protective liver effect mediated by XHP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggest that the HIF-1, FoxO, PI3K-Akt, insulin, and thyroid hormone signaling pathways are key modulators of XHP's effects. Finally, eight key targets including Mapk1, Mapk3, Akt1, Map2k1, Pik3ca, Pik3cg, Raf1, and Prkca were verified by molecular docking and proteomics analysis, which provide insight into the hepatoprotective effect observed with XHP treatment. Conclusion: In summary, these results improved upon knowledge of the chemical composition and the potential mechanisms of hepatoprotective action of oral XHP treatment, providing foundational support for this formulation as a viable therapeutic option for alcoholic liver disease.

Salt-contaminated water exposure induces gut microbial dysbiosis in chickens.

Microbes play a crucial role in maintaining health by aiding in digestion, regulating the immune system, producing essential vitamins, and preventing the colonization of harmful bacteria. The stability of the microbiota is, therefore, necessary for overall well-being. However, several environmental factors can negatively affect the microbiota, including exposure to industrial waste, i.e., chemicals, heavy metals, and other pollutants. Over the past few decades, industries have grown significantly, but the wastewater from those industries has seriously harmed the environment and the health of living beings both locally and globally. The current study investigated the effects of salt-contaminated water exposure on gut microbiota in chickens. According to our findings, amplicon sequencing showed 453 OTUs across control and salt-contaminated water exposure groups. Proteobacteria, Firmicutes, and Actinobacteriota were the most dominant phyla in the chickens regardless of treatment. However, exposure to salt-contaminated water resulted in a remarkable decline in gut microbial diversity. While, the beta diversity revealed substantial differences in major gut microbiota components. Moroever, microbial taxonomic investigation indicated that the proportions of one bacterial phylum and nineteen bacterial genera significantly decreased. Also, the levels of one bacterial phylum and thirty three bacterial genera markedly increased under salt-contaminated water exposure, which indicates a disruption in gut microbial homeostasis. Hence the current study provides a basis to explore the effects of salt-contaminated water exposure on the health of vertebrate species.

Structure of a new glycyrrhiza polysaccharide and its immunomodulatory activity.

A component of licorice polysaccharide (GPS-1) was extracted from licorice, its primary structure was identified and characterized for the first time, and its immunomodulatory activity was studied. Crude licorice polysaccharide was isolated and purified by DEAE sepharose FF ion-exchange column chromatography and Chromdex 200 PG gel filtration column chromatography to obtain a purified Glycyrrhiza polysaccharide named GPS-1. NMR and methylation analysis revealed that GPS-1 is composed of homogalacturonan (HG)-type pectin with 4)-D-GalpA-(1 as the backbone. This study of GPS-1 also examined its significant role in regulating immune activity in vitro and in vivo. As a result, GPS-1 promoted the secretion of IFN-γ and IL-4 in mice and increased the proportion of CD3+CD4+ and CD3+CD8+ T lymphocytes in their spleens. Dendritic cells (DCs) treated with GPS-1 showed promotion of DC maturation, antigen presentation, and phagocytic capacity. The results suggest that GPS-1 is a potential immunomodulator that stimulates the immune system by regulating multiple signaling pathways. Combined with our characterization of the primary structure of GPS-1, the present investigation provides the basis for future study of the form-function relationship of polysaccharides.

A Novel Deep-Learning Model Compression Based on Filter-Stripe Group Pruning and Its IoT Application.

Nowadays, there is a tradeoff between the deep-learning module-compression ratio and the module accuracy. In this paper, a strategy for refining the pruning quantification and weights based on neural network filters is proposed. Firstly, filters in the neural network were refined into strip-like filter strips. Then, the evaluation of the filter strips was used to refine the partial importance of the filter, cut off the unimportant filter strips and reorganize the remaining filter strips. Finally, the training of the neural network after recombination was quantified to further compress the computational amount of the neural network. The results show that the method can significantly reduce the computational effort of the neural network and compress the number of parameters in the model. Based on experimental results on ResNet56, this method can reduce the number of parameters to 1/4 and the amount of calculation to 1/5, and the loss of model accuracy is only 0.01. On VGG16, the number of parameters is reduced to 1/14, the amount of calculation is reduced to 1/3, and the accuracy loss is 0.5%.

In vitro and in vivo evaluation of a water-in-oil microemulsion of platycodin D.

Platycodin D (PD) is the active metabolite of Platycodon grandiflorum. The main purpose of this study was to develop and evaluate a water-in-oil (W/O) microemulsion formulation of PD (PD-ME). The PD-ME was successfully prepared by the water titration method at K m = 2, to draw the pseudoternary phase diagrams. Physical characterization including the particle size, pH, refractive index, average viscosity, and polydispersity index (PDI) was performed. The in vivo characteristics were evaluated by intestinal permeability and pharmacokinetic studies. The optimized microemulsion formulation consisted of 100 mg/ml PD aqueous solution, soybean phospholipids, ethanol, and oleic acid (27:39:19:15, w/w). The average viscosity, pH, droplet size, PDI, and zeta potential of the PD-ME were 78.65 ± 0.13 cPa•s, 5.70 ± 0.05, 30.46 ± 0.20 nm, 0.33 ± 0.00, and -3.13 mV, respectively. The drug concentration of the PD-ME was 26.3 ± 0.6 mg/ml. The PD-ME showed significantly higher apparent permeability coefficients than PD (p < .01). The pharmacokinetic studies showed that the PD-ME had significantly higher values of T 1/2 (2.26-fold), AUC0-24h (area under the curve; 1.65-fold), and MRT0-24h (1.58-fold) than PD (p < .01). It can be seen that W/O ME presents a strategy with great promise for enhancing the intestinal permeability and better oral absorption of drugs with high polarity and poor permeability.