TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000313735
  • Gene Name:NOS2
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qPCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:7,8-dihydroxyflavone
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:phenylketonuria
  • Tissue:

Other information

  • Title:7,8-dihydroxyflavone reduces lipid peroxidation, proinflammatory cytokines, and mediators in chemically induced-phenylketonuria model
  • Journal:Acta Neurobiologiae Experimentalis
  • Published:2024
  • PubMed ID:39392024
  • Abstract:Phenylketonuria (PKU) stems from a rare genetic metabolic imbalance attributed to an insufficiency in the enzyme phenylalanine hydroxylase. Within the context of PKU, brain-derived neurotrophic factor (BDNF) plays a pivotal role in brain function. 7,8-dihydroxyflavone (7,8-DHF) operates as a tropomyosin receptor kinase B (TrkB) agonist, mimicking the effects of BDNF. This study aimed to examine the effects of administering 7,8-DHF in chemically-induced rat models specifically induced to simulate PKU chemically. The rats were subcutaneously injected with phenylalanine and p-chlorophenylalanine, a phenylalanine hydroxylase inhibitor, along with 7,8-DHF. The injections began on the 2nd day after birth and continued until the 10th day. Levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-33 (IL-33), BDNF, malondialdehyde (MDA), monoamine oxidase (MAO), and superoxide dismutase (SOD) in the brain tissues were quantified using the enzyme-linked immunosorbent assay (ELISA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to assess the gene expressions of inducible nitric oxide synthase (iNOS), nuclear factor kappa beta (NF-κB), caspase-3, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and BDNF. The results showed a decrease in mRNA levels of iNOS, IL-1β, IL-6, and lipid peroxidation in the group that received 7,8-DHF. These results indicate that administering 7,8-DHF has the potential to reduce brain damage in PKU by lowering proinflammatory cytokine levels and lipid peroxidation in PKU models. Thus, 7,8-DHF, as a small molecule, might offer a promising adjunct therapeutic approach for PKU.
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