Protective Effect of Fustin against Huntington's Disease in 3-Nitropropionic Treated Rats via Downregulation of Oxidative Stress and Alteration in Neurotransmitters and Brain-Derived Neurotrophic Factor Activity.
May Nasser Bin-JumahSadaf Jamal GilaniAbdulaziz F AlabbasiFahad A Al-AbbasiShareefa A AlGhamdiOhoud Y AlshehriAmira M AlghamdiNadeem SayyedImran KazmiPublished in: Biomedicines (2022)
Researchers have revealed that Rhus verniciflua heartwood, which contains fustin as an important component, possesses antioxidant-mediated, anti-mutagenic, and anti-rheumatoid arthritis characteristics. Additionally, out of the numerous plant-derived secondary metabolites, there are various research papers concentrating on flavonoids for potential advantages in neurological illnesses. The current study aims to assess the neuroprotective potential of fustin in rodents over 3-nitropropionic acid (3-NPA)-induced Huntington's disease (HD)-like consequences. The efficacy of fustin 50 and 100 mg/kg was studied with multiple-dose administrations of 3-NPA, which experimentally induced HD-like symptoms in rats for 22 days. At the end of the study, several behavioral tests were performed including a beam walk, rotarod, and grip strength tests. Similarly, some biochemical parameters were assessed to support oxidative stress (reduced glutathione-GSH, superoxide dismutase-SOD, catalase-CAT, and malondialdehyde-MDA), alteration in neurotransmitters (gamma-aminobutyric acid-GABA-and glutamate), alteration in brain-derived neurotrophic factor activity, and nitrite levels. Additionally, pro-inflammatory parameters were carried out to evaluate the neuroinflammatory responses associated with streptozotocin such as TNF-α, IL-1β, and COX in the perfused brain. The fustin-treated group exhibited a significant restoration of memory function via modulation in behavioral activities. Moreover, 3-NPA altered biochemical, neurotransmitters, brain protein levels, and neuroinflammatory measures, which fustin efficiently restored. This is the first report demonstrating the efficacy of novel phytoconstituent fustin as a potential future candidate for the treatment of HD via offering neuroprotection by subsiding the oxidative and enzymatic activity in the 3-NPA experimental animal paradigm.
Keyphrases
- diabetic rats
- oxidative stress
- rheumatoid arthritis
- cerebral ischemia
- dna damage
- nitric oxide
- white matter
- signaling pathway
- ischemia reperfusion injury
- resting state
- small molecule
- type diabetes
- single cell
- ms ms
- human health
- working memory
- induced apoptosis
- high fat diet
- current status
- drug induced
- disease activity
- newly diagnosed
- functional connectivity
- risk assessment
- endoplasmic reticulum stress
- heat stress
- protein protein
- smoking cessation
- combination therapy
- cell cycle arrest
- pi k akt