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. 2022 Nov 23;10(12):3021.
doi: 10.3390/biomedicines10123021.

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-Jumah  1   2   3 , Sadaf Jamal Gilani  4 , Abdulaziz F Alabbasi  5 , Fahad A Al-Abbasi  6 , Shareefa A AlGhamdi  6   7 , Ohoud Y Alshehri  8 , Amira M Alghamdi  6 , Nadeem Sayyed  9 , Imran Kazmi  5
Affiliations

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-Jumah et al. Biomedicines. .

Abstract

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.

Keywords: 3-nitropropionic acid; Huntington’s disease; brain-derived neurotrophic factor; fustin; neuroprotection; tumor necrosis factor-α.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Fustin Structure.
Figure 2
Figure 2
Effect of fustin on beam walk test against 3-nitropropionic acid-induced Huntington’s-like effects in rats. Values are expressed as mean ± S.E.M. (n = 6). Values are statistically significant at # p < 0.05 vs. negative control group, *** p < 0.001 vs. 3-nitropropionic acid, respectively (One-way ANOVA followed by Tukey’s test).
Figure 3
Figure 3
Effect of fustin on gripping strength against 3-nitropropionic acid-induced Huntington’s-like effects in rats. Values are expressed as mean ± S.E.M. (n = 6). Values are statistically significant at # p < 0.05 vs. negative control group, *** p < 0.001 vs. 3-nitropropionic acid, respectively (One-way ANOVA followed by Tukey’s test).
Figure 4
Figure 4
Effect of fustin on rotarod test against 3-nitropropionic acid-induced Huntington’s-like effects in rats. Values are expressed as mean ± S.E.M. (n = 6). Values are statistically significant at # p < 0.05 vs. negative control group, *** p < 0.001 vs. 3-nitropropionic acid, respectively (Two-way ANOVA followed by Tukey’s test).
Figure 5
Figure 5
Effect of fustin on endogenous parameters against 3-nitropropionic acid-induced Huntington’s-like effects in rats (A) MDA, (B) GSH, (C) CAT, (D) SOD. Values are expressed as mean ± S.E.M. (n = 6). Values are statistically significant at # p < 0.05 vs. negative control group, * p < 0.05 vs. 3-nitropropionic acid, ** p < 0.01 vs. 3-nitropropionic acid, *** p < 0.001 vs. 3-nitropropionic acid, respectively (One-way ANOVA followed by Tukey’s test).
Figure 6
Figure 6
Effect of fustin on brain pro-inflammatory markers against 3-nitropropionic acid-induced Huntington’s-like effects in rats (A) COX, (B) IL-1β, (C) TNF-α. Values are expressed as mean ± S.E.M. (n = 6). Values are statistically significant at # p < 0.05 vs. negative control group, * p < 0.05 vs. 3-nitropropionic acid, ** p < 0.01 vs. 3-nitropropionic acid, *** p < 0.001 vs. 3-nitropropionic acid, respectively (One-way ANOVA followed by Tukey’s test).
Figure 7
Figure 7
Effect of fustin on enzymatic activity against 3-nitropropionic acid-induced Huntington’s-like effects in rats (A) GST, (B) SDH. Values are expressed as mean ± S.E.M. (n = 6). Values are statistically significant at # p < 0.05 vs. negative control group, * p < 0.05 vs. 3-nitropropionic acid, ** p < 0.01 vs. 3-nitropropionic acid, *** p < 0.001 vs. 3-nitropropionic acid, respectively (One-way ANOVA followed by Tukey’s test).
Figure 8
Figure 8
Effect of fustin on neurotransmitter levels against 3-nitropropionic acid-induced Huntington’s-like effects in rats (A) GABA, (B) Glutamate. Values are expressed as mean ± S.E.M. (n = 6). Values are statistically significant at # p < 0.05 vs. negative control group, * p < 0.05 vs. 3-nitropropionic acid, *** p < 0.001 vs. 3-nitropropionic acid, respectively (One-way ANOVA followed by Tukey’s test).
Figure 9
Figure 9
Effect of fustin on BDNF activity against 3-nitropropionic acid-induced Huntington’s-like effects in rats. Values are expressed as mean ± S.E.M. (n = 6). Values are statistically significant at # p < 0.05 vs. negative control group, * p < 0.05 vs. 3-nitropropionic acid, *** p < 0.001 vs. 3-nitropropionic acid, respectively (One-way ANOVA followed by Tukey’s test).
Figure 10
Figure 10
Effect of fustin nitrite level against 3-nitropropionic acid-induced Huntington’s-like effects in rats. Values are expressed as mean ± S.E.M. (n = 6). Values are statistically significant at # p < 0.05 vs. negative control group, *** p < 0.001 vs. 3-nitropropionic acid, respectively (One-way ANOVA followed by Tukey’s test).
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