Anti-Bacterial Agents ; pharmacology ; Child ; Dyspepsia ; drug therapy ; Erythromycin ; analogs & derivatives ; pharmacology ; therapeutic use ; Gastroesophageal Reflux ; drug therapy ; Gastrointestinal Motility ; drug effects ; Humans ; Motilin ; pharmacology ; Receptors, Gastrointestinal Hormone ; drug effects ; Receptors, Neuropeptide ; drug effects

Pseudo-allergic reactions (PARs) widely occur upon application of drugs or functional foods. Anti-pseudo-allergic ingredients from natural products have attracted much attention. This study aimed to investigate anti-pseudo-allergic compounds in licorice. The anti-pseudo-allergic effect of licorice extract was evaluated in rat basophilic leukemia 2H3 (RBL-2H3) cells. Anti-pseudo-allergic compounds were screened by using RBL-2H3 cell extraction and the effects of target components were verified further in RBL-2H3 cells, mouse peritoneal mast cells (MPMCs) and mice. Molecular docking and human MRGPRX2-expressing HEK293T cells (MRGPRX2-HEK293T cells) extraction were performed to determine the potential ligands of MAS-related G protein-coupled receptor-X2 (MRGPRX2), a pivotal target for PARs. Glycyrrhizic acid (GA) and licorice chalcone A (LA) were screened and shown to inhibit Compound48/80-induced degranulation and calcium influx in RBL-2H3 cells. GA and LA also inhibited degranulation in MPMCs and increase of histamine and TNF-α in mice. LA could bind to MRGPRX2, as determined by molecular docking and MRGPRX2-HEK293T cell extraction. Our study provides a strong rationale for using GA and LA as novel treatment options for PARs. LA is a potential ligand of MRGPRX2.
Animals ; Anti-Allergic Agents/therapeutic use* ; Calcium/metabolism* ; Cell Degranulation ; Glycyrrhiza ; HEK293 Cells ; Humans ; Hypersensitivity/drug therapy* ; Mast Cells/metabolism* ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Nerve Tissue Proteins/metabolism* ; Rats ; Receptors, G-Protein-Coupled/metabolism* ; Receptors, Neuropeptide/therapeutic use*

Promoter CpG island hypermethylation has become recognized as an important mechanism for inactivating tumor suppressor genes or tumor-related genes in human cancers of various tissues. Gene inactivation in association with promoter CpG island hypermethylation has been reported to be four times more frequent than genetic changes in human colorectal cancers. Hepatocellular carcinoma is also one of the human cancer types in which aberrant promoter CpG island hypermethylation is frequently found. However, the number of genes identified to date as hypermethylated for hepatocellular carcinoma (HCC) is fewer than that for colorectal cancer or gastric cancer, which can be attributed to fewer attempts to perform genome-wide methylation profiling for HCC. In the present study, we used bead-array technology and coupled methylation-specific PCR to identify new genes showing cancer-specific methylation in HCC. Twenty-four new genes have been identified as hypermethylated at their promoter CpG island loci in a cancer-specific manner. Of these, TNFRSF10C, HOXA9, NPY, and IRF5 were frequently hypermethylated in hepatocellular carcinoma tissue samples and their methylation was found to be closely associated with inactivation of gene expression. Further study will be required to elucidate the clinicopathological implications of these newly found DNA methylation markers in hepatocellular carcinoma.
Antimetabolites, Antineoplastic/therapeutic use ; Azacitidine/analogs & derivatives/therapeutic use ; Carcinoma, Hepatocellular/drug therapy/*genetics ; Cell Line, Tumor ; CpG Islands ; *DNA Methylation ; GPI-Linked Proteins/genetics ; Gene Expression Profiling ; Homeodomain Proteins/genetics ; Humans ; Interferon Regulatory Factors/genetics ; Liver Neoplasms/drug therapy/*genetics ; Neuropeptide Y/genetics ; Oligonucleotide Array Sequence Analysis ; Promoter Regions, Genetic ; Tumor Necrosis Factor Decoy Receptors/genetics