Dataset Information

Identification of a specific agonist of human TAS2R14 from Radix Bupleuri through virtual screening, functional evaluation and binding studies.

ABSTRACT: Bitter taste receptors (TAS2Rs) have attracted a great deal of interest because of their recently described bronchodilator and anti-inflammatory properties. The aim of this study was to identify natural direct TAS2R14 agonists from Radix Bupleuri that can inhibit mast cell degranulation. A ligand-based virtual screening was conducted on a library of chemicals contained in compositions of Radix Bupleuri, and these analyses were followed by cell-based functional validation through a HEK293-TAS2R14-G16gust44 cell line and IgE-induced mast cell degranulation assays, respectively. Saikosaponin b (SSb) was confirmed for the first time to be a specific agonist of TAS2R14 and had an EC50 value of 4.9??M. A molecular docking study showed that SSb could directly bind to a TAS2R14 model through H-bond interactions with Arg160, Ser170 and Glu259. Moreover, SSb showed the ability to inhibit IgE-induced mast cell degranulation, as measured with a ?-hexosaminidase release model and real-time cell analysis (RTCA). In a cytotoxicity bioassay, SSb showed no significant cytotoxicity to HEK293 cells within 24?hours. This study demonstrated that SSb is a direct TAS2R14 agonist that inhibit IgE-induced mast cell degranulation. Although the target and in vitro bioactivity of SSb were revealed in this study, it still need in vivo study to further verify the anti-asthma activity of SSb.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC5610306 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of a specific agonist of human TAS2R14 from Radix Bupleuri through virtual screening, functional evaluation and binding studies.

Zhang Yuxin Y Wang Xing X Li Xi X Peng Sha S Wang Shifeng S Huang Christopher Z CZ Huang Corine Z CZ Zhang Qiao Q Li Dai D Jiang Jun J Ouyang Qin Q Zhang Yanling Y Li Shiyou S Qiao Yanjiang Y

Scientific reports 20170922 1

Bitter taste receptors (TAS2Rs) have attracted a great deal of interest because of their recently described bronchodilator and anti-inflammatory properties. The aim of this study was to identify natural direct TAS2R14 agonists from Radix Bupleuri that can inhibit mast cell degranulation. A ligand-based virtual screening was conducted on a library of chemicals contained in compositions of Radix Bupleuri, and these analyses were followed by cell-based functional validation through a HEK293-TAS2R14 ...[more]

PMID: 28939897

Similar Datasets

Project description:Viral hepatitis B is caused by the hepatitis B virus, which is characterized by liver lesions. Bupleuri Radix and Scutellariae Radix are the main traditional medicine pairs with remarkable efficacy in hepatitis B. However, their molecular mechanisms are incompletely understood. The main active components of Bupleuri Radix and Scutellariae Radix, as well as therapeutic targets for the treatment of hepatitis B, were identified through network pharmacology techniques. We identified viral hepatitis B targets using the GeneCards, online mendelian inheritance in man, and therapeutic target databases. We discovered the active components of Bupleuri Radix and Scutellariae Radix as well as therapeutic targets using the encyclopedia of traditional Chinese medicine, HERB, traditional Chinese medicine systems pharmacology database, and a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine databases. VENNY obtained the intersections. Cytoscape and STRING were used to create the “active ingredient-potential target” network and protein interaction network. The DAVID database was used to enrich GO and KEGG pathways. The results were confirmed using the molecular docking method. There were 1827 viral hepatitis B targets, and 37 active ingredients for Bupleuri and Scutellariae Radix, with the main components being quercetin, wogonin, baicalein, and kaempferol. Tumor necrosis factor (TNF), mitogen-activated protein kinase 3 (MAPK3), interleukin-6 (IL-6), vascular endothelial growth factor A, cysteinyl aspartate specific proteinase 3, transcription factor AP-1 (JUN), RAC-alpha serine/threonine-protein kinase, and cellular tumor antigen p53 are among the 78 common targets of Bupleuri Radix and Scutellariae Radix intervention in viral hepatitis B. KEGG enrichment resulted in 107 pathways, including cancer, hepatitis B, and TNF signaling pathways. According to the molecular docking technique, quercetin, wogonin, baicalein, and kaempferol had strong binding activities with TNF, MAPK3, and IL-6. In this study, we initially identified various molecular targets and multiple pathways involved in hepatitis B treatment with Bupleuri Radix and Scutellariae Radix.

Dataset Information

Identification of a specific agonist of human TAS2R14 from Radix Bupleuri through virtual screening, functional evaluation and binding studies.

Publications

Identification of a specific agonist of human TAS2R14 from Radix Bupleuri through virtual screening, functional evaluation and binding studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets