Résumé
Acute liver failure （ALF） is one of the most critical liver diseases in clinical practice and seriously affects the life and health of Chinese people. Due to its high morbidity and mortality rates， unclear pathogenesis， and limited treatment methods， ALF has become a major problem that needs to be solved urgently in the field of liver diseases. In recent years， more and more studies have shown that endoplasmic reticulum stress is a key biological process in the progression of ALF， and the IRE1α/TRAF2/JNK pathway， as a part of endoplasmic reticulum stress signaling， plays a role in amplifying inflammatory response， promoting hepatocyte apoptosis， and inhibiting liver regeneration ability during the progression of diseases. As a traditional treasure of China， traditional Chinese medicine has become a research hotspot in search for effective prevention and treatment drugs for ALF from monomers of Chinese herbs. This article elaborates on the mechanism of action of the IRE1α/TRAF2/JNK pathway in the progression of ALF and summarizes the potential value of several monomers of Chinese herbs in regulating this pathway， such as salidroside， Fructus Broussonetiae， Fructus Psoraleae+Schisandra chinensis， baicalein， genipin， kaempferol， resveratrol， sea buckthorn polysaccharide extract， and luteol， in order to provide a reference for further research and clinical practice of ALF.
Résumé
ObjectiveTo mine the compatibility rules of patented traditional Chinese medicine (TCM) compound prescriptions for treating chronic atrophic gastritis (CAG) by systems pharmacology and molecular docking methods, and predict the targets and molecular mechanisms of Chinese medicinals with different efficacy in the treatment of CAG. MethodThe TCM compound prescriptions for treating CAG were extracted from the patent system of the China National Intellectual Property Administration. The active components and targets of the prescriptions were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrative Database (TCMID), and UniProt. The candidate targets and pathways of CAG were obtained from GeneCards, DisGeNet, Online Mendelian Inheritance in Man (OMIM), MalaCards, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome. The gene ontology (GO) functional annotation and KEGG pathway enrichment were realized by R Studio 4.1.2. STRING11.0 was employed to build the protein-protein interaction (PPI) network, and AutoDock Vina 4.2.6 was used for the docking between key targets and components. ResultA total of 228 TCM compound prescriptions for treating CAG were extracted. The medicinals used in these prescriptions mainly had warm or cold nature, bitter or sweet taste, tropism to the spleen, stomach, and liver meridians, and the efficacy of tonifying Qi, regulating Qi movement, clearing heat, and activating and toniying blood. The prescriptions mainly treated CAG via p53, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), forkhead box protein O (FoxO), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1 (HIF-1) signaling pathways. Molecular docking results confirmed that the active components in the prescriptions had docking activities with key receptor proteins. ConclusionThis study preliminarily analyzed the compatibility rules of TCM compound prescriptions in the treatment of CAG. The medicinals with different efficacy treat CAG by regulating cell proliferation, apoptosis, and oxidative stress response, preventing carcinogen production, promoting gastric acid secretion, and improving local microcirculation in a multi-target, multi-pathway, multi-link manner. The findings facilitate the research on the TCM treatment of CAG.
Résumé
The cytochrome P450 (CYP) family is the most important drug-metabolizing enzyme in human body and is responsible for the metabolism of endogenous and exogenous compounds. As the main site of the expression of the CYP family, the liver is the metabolic center of drugs, and in recent years, the role of the CYP family in the liver has attracted wide attention from the scholars in China and globally. This article reviews the distribution differences of the CYP family from the aspects of anatomy, genetics, and genomics, changes in the expression of the CYP family in the pathological processes such as non-alcoholic fatty liver disease, alcoholic liver disease, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma, and the effect of CYP family-mediated enzyme activity on the treatment effect of pharmacotherapy for metabolic-associated liver diseases, in order to provide important enlightenment for identifying key drug intervention targets in diseases and enhancing clinical efficacy and safety.