RESUMEN
Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.
Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Coenzima A Ligasas/metabolismo , Coenzima A Ligasas/farmacología , Dieta Alta en Grasa/efectos adversos , Ácidos Grasos/metabolismo , Ácidos Grasos/farmacología , Ácidos Grasos/uso terapéutico , Metabolismo de los Lípidos , Hígado , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Ácido Oléico/metabolismo , Ácido Oléico/farmacología , Ácido Oléico/uso terapéuticoRESUMEN
Objective:To explore the ingredients, targets, and mechanisms of Hanchuan Zupa Granules in the treatiment of Influenza A virus.Methods:By using Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform (TCMSP), GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGkb), Therapeutic target database (TTD) and DrugBank database to obtain relevant components and targets of Hanchuan Zupa Granules in the treatment of Influenza A virus; R software was used for the obtain of Hanchuan Zupa Granules -Influenza A virus intersection targets; Cytoscape software was applied for the construction of "Hanchuan Zupa Granules-component-target" network; Protein-protein interaction network (PPI) and topological analysis were constructed by STRING database and Cytoscape software. Intersection targets for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted by R software; Auto Dock Tools were used for molecular docking.Results:All together 111 potential active ingredients, with corresponding 131 targetswere identified from Hanchuan Zupa Granules in the treatment of Influenza A virus. Quercetin, apigenin, luteolin, kaempferol, wogonin, etc. are included as core ingredients. STAT3, MAPK1, MAPK3, AKT1, JUN, etc. are included as core targets. Intersection targets were mainly enriched in 178 signal pathways such as IL-17 signal pathway, influenza A signal pathway, TNF signal pathway, etc; Molecular docking showed that core component had a good affinity with the target.Conclusion:Hanchuan Zupa Granules could play the role of anti-Influenza A virus with multi-component-multi-target-multi-pathway,characteristics, and this syudy provide a basis for future experimental research on its mechanism.
RESUMEN
Diabetic peripheral neuropathy is a common complication of diabetes, and its pathogenesis is complex. Its high morbidity can result in disability, teratogenesis, and death in diabetic patients. At present, the pathogenesis of diabetic peripheral neuropathy has not been clearly elucidated, which may be related to oxidative stress, inflammatory response, microcirculation dysfunction, metabolic abnormalities, etc. Recent studies have found that apoptosis plays an important role in the pathogenesis of diabetic peripheral neuropathy. The three pathways, i.e., mitochondrial pathway, death receptor pathway, and endoplasmic reticulum pathway, jointly regulate the cell apoptosis in the body. Traditional Chinese medicine, with definite efficacies in the treatment of diabetic peripheral neuropathy, is advantageous in overall regulation and multi-target and multi-pathway treatment. As reported, the active ingredients in Chinese medicine and Chinese medicinal compounds can alleviate diabetic peripheral neuropathy by regulating apoptosis signaling pathways. Furthermore, apoptosis pathways are expected to be potential targets for new drugs against diabetic peripheral neuropathy following oxidative stress. Therefore, this paper, taking apoptosis as the entry point, reviewed the research progress on TCM intervention in diabetic peripheral neuropathy in recent years to provide references for the clinical prevention and treatment of diabetic peripheral neuropathy and the development of new drugs.