Investigation of the mechanism of Prunella vulgaris in treatment of papillary thyroid carcinoma based on network pharmacology integrated molecular docking and experimental verification.

To analyze the molecular mechanism of Prunella vulgaris L. (PV) in the treatment of papillary thyroid carcinoma (PTC) by using network pharmacology combined with molecular docking verification. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used to predict the main active components of PV, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, PubChem, and Swiss Target Prediction databases were used to obtain the corresponding targets of all active components. Targets collected for PTC treatment through Gene Cards, Digest and Online Mendelian Inheritance in Man databases respectively. The Search Tool for the Retrieval of Interaction Gene/Protein database was used to obtain the interaction information between proteins, and the topology analysis and visualization were carried out through Cytoscape 3.7.2 software (https://cytoscape.org/). The R package cluster profiler was used for gene ontology and Kyoto encyclopedia of genes and genomes analysis. The "active ingredient-target-disease" network was constructed by using Cyto scape 3.7.2, and topological analysis was carried out to obtain the core compound. The molecular docking was processed by using Discovery Studio 2019 software, and the core target and active ingredient were verified. The inhibition rate was detected by CCK8 method. Western blot was used to detect the expression levels of kaempferol anti-PTC related pathway proteins. A total of 11 components and 83 corresponding targets in the component target network of PV, of which 6 were the core targets of PV in the treatment of PTC. It was showed that quercetin, luteolin, beta (ß)-sitosterol, kaempferol may be the core components of PV in the treatment of PTC. vascular endothelial growth factor A, tumor protein p53, transcription factor AP-1, prostaglandin endoperoxidase 2, interleukin 6, and IL-1B may be important targets for the treatment of PTC. The main biological processes mainly including response to nutrient levels, response to xenobiotic stimulus, response to extracellular stimulus, external side of plasma membrane, membrane raft, membrane microdomain, serine hydrolase activity, serine-type endopeptidase activity, antioxidant activity, etc IL-17 signaling pathway, and PI3K-Akt signaling pathway may affect the recurrence and metastasis of PTC. Kaempferol may significantly reduce the activity of Papillary cells of human thyroid carcinoma bcpap cell lines cells compared with quercetin, luteolin, ß-sitosterol. Kaempferol may reduce the protein expression levels of interleukin 6, vascular endothelial growth factor A, transcription factor AP-1, tumor protein p53, 1L-1B and prostaglandin endoperoxidase 2, respectively. PV has the characteristics of multi-components, multi-targets and multi- pathways in the treatment of PTC, which network pharmacology help to provides a theoretical basis for the screening of effective components of PV and further research.

Protective effect and mechanism of ginsenoside Rg1 on carbon tetrachloride­induced acute liver injury.

Liver injury is a common pathological state in various types of liver disease; severe or persistent liver damage is the basis of hepatic failure. Ginsenoside Rg1 (Rg1), one of the primary active ingredients of ginseng, has been reported to reduce concanalin A­induced hepatitis and protect against lipopolysaccharide­ and galactosamine­induced liver injury. However, the underlying protective mechanism of Rg1 in acute liver injury remains unclear. In the present study, a carbon tetrachloride (CCl4)­induced acute liver injury model was established, and the protective effect of Rg1 on CCl4­induced acute liver injury was demonstrated in cell culture and animal experimental systems. Further investigation of the mechanisms demonstrated that pretreatment with Rg1 reduced elevated levels of alanine aminotransferase and aspartate aminotransferase, enhanced the antioxidant activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) content. Experiments in vitro demonstrated that Rg1 decreased p65 expression and inhibited nuclear factor (NF)­κB activity. In addition to the effect of Rg1, an NF­κB inhibitor promoted cell survival, enhanced SOD activity and reduced MDA level. It was observed through in vivo experiments that pretreatment with Rg1 inhibited NF­κB expression and activity in Kupffer cells and reduced the serum levels of tumor necrosis factor­α and interleukin­6. In conclusion, the results of the present study indicated that pretreatment with Rg1 may rescue CCl4­induced acute liver injury in vivo and in vitro through inhibition of NF­κB activity, to restore the anti­oxidative defense system and down­regulate pro­inflammatory signaling pathways. The present observations provide a theoretical foundation for the clinical application of Rg1 therapy in acute liver injury.