ABSTRACT
AIMS: Phenylketonuria (PKU), which is caused by mutations in the phenylalanine hydroxylase (PAH) gene, is one of the most common inherited diseases of amino acid metabolism. Phenylketonuria is characterized by an abnormal accumulation of phenylalanine and its metabolites in body fluids and brain tissues, subsequently leading to severe brain dysfunction. Various pathophysiological and molecular mechanisms underlying brain dysfunction in PKU have been described. However, the metabolic changes and their impacts on the function of cerebral cortices of patients with PKU remain largely unknown. METHODS: We measured the levels of small molecule metabolites in the cerebrocortical tissues of PKU mice and wild-type control mice using liquid chromatography-mass spectrometry (LC-MS)-based metabolome analysis. Differential metabolites were further subjected to metabolic pathway and enrichment analysis. RESULTS: Metabolome analysis revealed 35 compounds among 143 detected metabolites were significantly changed in PKU mice as compared to those in their wild-type littermates. Metabolic pathway and enrichment analysis of these differential metabolites showed that multiple metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis; valine, leucine, and isoleucine biosynthesis; alanine, aspartate, and glutamate metabolism; purine metabolism; arginine and proline metabolism and methionine metabolism, were impacted in the cerebral cortices of PKU mice. CONCLUSIONS: The data revealed that multiple metabolic pathways in cerebral cortices of PKU mice were disturbed, suggesting that the disturbances of the metabolic pathways might contribute to neurological or neurodevelopmental dysfunction in PKU, which could thus provide new insights into brain pathogenic mechanisms in PKU as well as mechanistic insights for better understanding the complexity of the metabolic mechanisms of the brain dysfunction in PKU.
Subject(s)
Cerebral Cortex/metabolism , Disease Models, Animal , Metabolic Networks and Pathways/physiology , Metabolomics/methods , Phenylalanine Hydroxylase/metabolism , Phenylketonurias/metabolism , Animals , Male , Mice , Mice, Knockout , Mice, Transgenic , Phenylalanine Hydroxylase/deficiency , Phenylalanine Hydroxylase/genetics , Phenylketonurias/geneticsABSTRACT
Bioassay-guided fractionation of the acetone extract of the twigs of Garcinia nujiangensis resulted in the isolation of four new prenylated xanthones, nujiangexanthones C-F (1-4), and ten known related analogues. The structures of compounds 1-4 were elucidated by interpretation of their spectroscopic data. The compounds isolated were evaluated for their cytotoxic effects against three cancer cell lines, the test substances demonstrated selectivity toward the cancer cells.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Garcinia/chemistry , Xanthones/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Humans , Molecular Structure , Xanthones/isolation & purificationABSTRACT
A new and a known anthraquinone glycosides were isolated from the ethanol extract of the roots of Rheum officinale Baill. The extract was purified by various chromatographies, such as silica gel, Sephadex LH-20, RP-C18 column chromatography and HPLC. Two compounds were identified by the spectroscopic techniques of NMR, MS, and chemical method. In addition, they were tested for their cytotoxic effects against HepG2 cell. Unfortunately, they showed no or weak activity.
Subject(s)
Anthraquinones/isolation & purification , Glycosides/isolation & purification , Rheum/chemistry , Anthraquinones/chemistry , Anthraquinones/pharmacology , Glycosides/chemistry , Glycosides/pharmacology , Hep G2 Cells , Humans , Molecular Structure , Plant Roots/chemistry , Plants, Medicinal/chemistryABSTRACT
Bioassay-guided fractionation of the acetone extract of the leaves of Garcinia nujiangensis resulted in the isolation of two new prenylated xanthones, nujiangexanthones A (1) and B (2), three new polycyclic polyprenylated acylphloroglucinols, nujiangefolins A-C (3-5), and 10 known related analogues. The structures of compounds 1-5 were elucidated by interpretation of their spectroscopic data. Compounds 3 and 4 are unusual polycyclic polyprenylated acylphloroglucinols in which the enol hydroxy group forms a six-membered ring with a benzene ring carbon. The compounds isolated were evaluated for their cytotoxic effects against 11 cancer cell lines and immortalized MIHA normal liver cells, and the test substances demonstrated selectivity toward the cancer cells. Isojacareubin (6) was found to be the most potent cytotoxic compound of those tested.
