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Cyanidin-3-O-glucoside alleviates trimethyltin chloride-induced neurodegeneration by maintaining glutamate homeostasis through modulation of the gut microbiota

Yu Xi, Wenhui Li, Junru Wang, Meihong Yu, Xiangquan Zeng, He Li(), Jian Li()
Key Laboratory of Green and Low-Carbon Processing Technology for Plant-Based Food of China National Light Industry Council, Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China

Peer review under responsibility of Tsinghua University Press.

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Highlights

• C3G ameliorates TMT-induced hippocampal neurodegeneration and synaptic dysfunction.

• Glutamate brain homeostasis disruption in neurodegeneration is restored by C3G.

• Glutamine synthetase was critical to the C3G neuroprotective effects.

• Modulation of gut microbiota protects astrocytes and glutamate brain homeostasis.

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Abstract

Trimethyltin chloride (TMT) is a potent neurotoxin to cause neurodegeneration, especially in hippocampus. This study aimed to identify dietary components that can effectively attenuate TMT-induced neurodegeneration in humans. The predominant anthocyanin in human diets, cyanidin-3-O-glucoside (C3G, 5 or 50 mg/kg), was given to mice for 16 days, and TMT (2.7 mg/kg) was injected intraperitoneally once on the eighth day. C3G (50 mg/kg) significantly alleviated TMT-induced seizures and subsequent cognitive impairment by ameliorating hippocampal neurodegeneration and synaptic dysfunction. Furthermore, C3G treatment restored glutamate homeostasis in brain and reversed glutamine synthetase (GS) inhibition in reactive astrogliosis and neuroinflammation, which are critical for C3G’s neuroprotective effects. Notably, C3G decreased the lipopolysaccharide, tumor necrosis factor-α, interleukin-6, and interleukin-1β levels in the mice, which potentially by modulating the relative abundance of Atopobiaceae and Lachnospiraceae in the gut. C3G may be a promising and practical dietary component for reducing TMT-induced neurodegeneration.

Keywords

Cyanidin-3-O-glucosideTrimethyltinNeurodegenerationGlutamatergic pathwayGut microbiota

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Food Science and Human Wellness
Volume 13 Issue 2,
March 2024
Pages 1093-1107
DOI: 10.26599/FSHW.2022.9250141
Cite this article:
Xi Y, Li W, Wang J, et al. Cyanidin-3-O-glucoside alleviates trimethyltin chloride-induced neurodegeneration by maintaining glutamate homeostasis through modulation of the gut microbiota. Food Science and Human Wellness, 2024, 13(2): 1093-1107. https://doi.org/10.26599/FSHW.2022.9250141
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