RESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a global disease with growing prevalence that is difficult to cure. Rosa roxburghii Tratt is an edible and medicinal plant, and modern pharmacological studies have shown that it has potential anti-diabetic activity. This is the first study to explore the active components and potential mechanisms of Rosa roxburghii Tratt fruit for treating T2DM based on UPLC-Q-Exactive Orbitrap/MS and network pharmacology. METHODS: The active components of Rosa roxburghii Tratt fruit were obtained from UPLC-Q-Exactive Orbitrap/MS analysis and retrieval in the SciFinder, PubMed, Web of Science, and CNKI databases. The potential targets of the active components were obtained from the SwissTargetPrediction and PharmMapper databases. The disease targets for T2DM were obtained from GeneCards, OMIM, TTD, DisGENent, and GEO databases. The intersection of the two datasets was used to obtain the potential targets of Rosa roxburghii Tratt fruit against T2DM. The target protein interaction network was constructed using the String database and Cytoscape software. The R software ClusterProfiler package was used for target enrichment analysis and the Cytoscape CytoNCA plug-in was used to screen core targets. Molecular docking and result visualization were performed using PyMOL and Autodock Vina software. RESULTS: We obtained 20 bioactive ingredients, including alphitolic acid, quercetin, and ellagic acid, as well as 13 core targets, such as AKT1, TNF, SRC, and VEGFA. All bioactive ingredients in Rosa roxburghii Tratt fruit were active against T2DM-related therapeutic targets. Rosa roxburghii Tratt fruit may play a therapeutic role in T2DM by regulating the PI3K/AKT, RAS, AGE-RAGE, and other signaling pathways. CONCLUSIONS: This study explored the active components and potential mechanisms of Rosa roxburghii Tratt fruit in the treatment of T2DM, laying the foundation for a further experimental study based on pharmacodynamic substances and their mechanisms of action.
RESUMO
The NF-κB family is a set of evolutionarily conserved transcription factors that play central roles in various biological events. Dorsal is an invertebrate NF-κB family member that is essential for the regulation of immune responses. In the current study, the Dorsal gene from Scylla paramamosain (SpDorsal) was identified, which showed high homology to other crustacean Dorsal proteins. Expression of SpDorsal was highest in hemocytes and could be significantly changed after immune stimulations. In expression vector-transfected S2 cells, SpDorsal was mainly localized in the cytoplasm and could be efficiently translocated into the nucleus upon immune stimulations with the Gram-positive bacteria Staphylococcus aureus and poly (I:C), but not the Gram-negative bacteria Vibrio parahaemolyticus. As a transcription factor, SpDorsal could activate the promoter of S. paramamosain Hyastatin (SpHyastatin) in vitro, while S. paramamosain Cactus (SpCactus), a homolog of IκB, could interact with SpDorsal to prevent its nuclear translocation and inhibit its transcription factor activity. Silencing of SpDorsal in vivo using RNAi strategy significantly increased the mortality of crabs infected with S. aureus but not that with V. parahaemolyticus. These indicated that the SpDorsal signaling pathway could be mainly implicated in immune responses against Gram-positive bacterial infection in S. paramamosain.