Astragaloside IV alleviates neuronal ferroptosis in ischemic stroke by regulating fat mass and obesity ‐associated—N6‐methyladenosine—acyl‐CoA synthetase long‐chain family member 4 axis

Ischemic stroke (IS) is a detrimental neurological disease with limited treatments options. Astragaloside IV (As-IV) was a promising bioactive constituent in the treatment of IS. In our study, As-IV promoted the transcription of fat mass and obesity-associated (Fto) by upregulating activating transcription factor 3(Atf3), resulting in a decrease of long-chain acyl-CoA synthetase-4 (Acsl4) N6-methyladenosine (m6A) levels, thus improving neuronal injury in IS by inhibiting ferroptosis. These findings provided a better understanding of the molecular mechanisms underlying the neuroprotective effects of As-IV and led to novel therapeutic targets for the treatment of IS. AbstractIschemic stroke (IS) is a detrimental neurological disease with limited treatment options. Astragaloside IV (As-IV) was a promising bioactive constituent in the treatment of IS. However, the functional mechanism remains unclear. Here, IS cell and mouse models were established by oxygen glucose deprivation/re-oxygenation (OGD/R) and middle cerebral artery occlusion (MCAO). Quantitative reverse transcription PCR (RT –qPCR), Western blotting, or Immunofluorescence staining measured related gene and protein expression of cells or mice brain tissues, and the results revealed altered expression of acyl-CoA synthetase long-chain family member 4 (Acsl4), fat mass and obesity-associated (Fto), and activation transcr iption factor 3 (Atf3) after treatment with As-IV. Then, increased N6-methyladenosine (m6A) levels ...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research