TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000216117
  • Gene Name:HMOX1
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:NRF2 signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:astragaloside IV
  • Drug Method:up-regulated the gene expression

Disease basic infommation

  • Disease:cognitive diseases
  • Tissue:tissues

Other information

  • Title:Astragaloside IV-induced Nrf2 nuclear translocation ameliorates lead-related cognitive impairments in mice
  • Journal:Biochimica et Biophysica Acta-molecular Cell Research
  • Published:2020
  • PubMed ID:32941941
  • Abstract:Recently, oxidative stress is a common denominator in the pathogenesis of metal-induced neurotoxicity. Thus, antioxidant therapy is considered as a promising strategy for treating lead-related cognitive impairment. Here, we tested the hypothesis that astragaloside IV (AS-IV) ameliorates lead-associated cognitive deficits through Nrf2-dependent antioxidant mechanisms. Male Nrf2-KO and WT mice received drinking water with 2000 ppm lead and/or AS-IV by gavage for 8 weeks starting at 4 weeks of age. Morris water maze test and biochemical assays were employed to study cognition-enhancing and antioxidant effects of AS-IV. The signaling pathways involved were analyzed using RT-PCR and western blot technology. Significantly, AS-IV attenuated Morris water maze-based cognitive impairment in lead-intoxicated mice. Importantly, cognition-enhancing effect of AS-IV was lost in Nrf2-KO mice. In parallel, AS-IV suppressed lead acetate (PbAc)-induced oxidative stress, as measured by MDA. Mechanistically, AS-IV can up-regulate the expressions of the GCLc and HO-1 at the level of transcription and translation, but not SOD, TrxR activity, GCLm, Trx1, and NQO1 expression. Interestingly, AS-IV induced accumulation of Nrf2 in the nucleus, whereas Nrf2 mRNA levels were unchanged. Furthermore, AS-IV treatment resulted in elevated levels of phosphorylated Akt (active form) and phosphorylated GSK-3β (inactive forms) but decreased level of phosphorylated Fyn. Collectively, our findings indicate that AS-IV may target Nrf2 to attenuate lead-triggered oxidative stress and subsequent cognitive impairments, suggesting that AS-IV is a potential candidate for the treatment of lead-associated cognitive diseases.
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