Cinnamaldehyde Regulates the Generation of γ‐aminobutyric Acid to Exert Sedation via Irreversible Inhibition of ENO1 in the Cerebellar Granular Layer. Issue 11 (30th March 2022)

• Record Type: Journal Article
• Authors: Ma, Xiaoyao; Liu, Kaixin; Han, Yiman; Bai, Yongping; Shen, Fukui; Wang, Mukuo; Wei, Wei; Qin, Jianfeng; Hao, Erwei; Hou, Xiaotao; Hou, Yuanyuan; Bai, Gang
• Is Part Of: Molecular nutrition & food research. Volume 66:Issue 11(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-30
• Subjects: cinnamaldehyde -- covalent binding -- ENO1 -- GABA -- sedation; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.202100963
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : Scope: Glutamate (Glu) and γ‐aminobutyric acid (GABA) are the major excitatory and inhibitory neurotransmitters that control information flow in the brain. GABA dysfunction is a general vulnerability factor for mental illness. Cinnamaldehyde (CA) is found to have sedation in a mental illness model. However, the specific targets and molecular mechanisms related to the sedative effects of CA have not been elucidated. Methods and Results: Metabolomics analysis and target fishing showed CA could increase the expression of GABA in vivo, and α‐enolase (ENO1) is the primary target protein of CA associated with sedation. CA mainly binds with ENO1 in the cerebellar granular layer of brain, which influences the first transformations of the input signals arriving in the cerebellar cortex. The α, β‐unsaturated aldehyde group of CA blocks the hydroxy group of Ser40, which induces a loss in ENO1 activation. CA also disturbs the glycolysis pathway and influences the tricarboxylic acid cycle and oxidative phosphorylation, which activate gluconeogenesis to provide energy to the brain. This mechanism is verified in zebrafish with ENO1 or glutamic acid decarboxylase (GAD) deficiency. Conclusions: CA demonstrates sedation and alleviates GABA dysfunction via covalent binding ENO1, which shows the potential to improve the therapy of mental illness. Abstract : Cinnamaldehyde (CA), a yellowish volatile oil, is the main compound of cinnamon. The α, β‐unsaturated aldehyde group of CA blocked the Ser40 of ENO1 in the cerebellar cortex, which disturbed the glycolysis pathway and influenced the tricarboxylic acid cycle. The process caused the expression enhance of GABA, which was the molecular mechanisms of CA's sedative effects.