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1- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
2- Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
3- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:  
Purpose: Alpha-mangostin (α-MG), the most prevalent xanthone found in Garcinia mangostana Linn,  has been documented to possess antioxidant and anti-inflammatory properties.  This study investigated the protective effects of α-MG against cuprizone (CZ)-induced demyelination in the corpus callosum (CC) of mice, as an animal model of multiple sclerosis.
Method: A chaw containing 0.4 % (w/w) CZ was used to feed adult female C57BL/6 mice for 5 weeks. Mice were divided into 6 groups: 1) The control group was fed a normal diet. 2) CPZ group. 3,4,5) Mice were fed with CZ diet + α-MG (20, 40 and 80 mg/kg by gavage). 6) Mice fed a normal diet + 80 mg/kg α-MG. After five weeks of administration, the levels of MDA and apoptotic markers, such as Bax, Bcl2, cleaved caspase-3, and inflammation factor TNF-α, were measured in CC.
Results: Compared with the control group, the CZ group lost weight (p<0.0001). In the CZ group, there was an increased amount of MDA (p<0.01) and noticeable increases in the Bax/Bcl2 ratio, cleaved caspase-3 (p<0.0001), and TNF-α (p<0.001) compared with the control group. Compared to the CZ group, using α-MG 80 mg/kg significantly increased body weight (p<0.01). In addition, α-MG at 20, 40, and 80 mg/kg decreased the MDA content (p<0.01, p<0.001, and p<0.0001, respectively). Administration of α-MG 80 mg/kg decreased the Bax/Bcl2 ratio, cleaved caspase-3 (p<0.0001), and TNF-α levels (p<0.0001).
Conclusion: Our data illustrate that α-MG can eliminate destructive CZ effects in CC by decreasing oxidative stress, inflammation and apoptosis.
Type of Study: Original | Subject: Cellular and molecular Neuroscience
Received: 2023/05/7 | Accepted: 2024/05/25

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