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• W4313236411 abstract "Kynurenine (KYN) accumulation in periphery induces brain injury, responsible for depression. α-Asarone is a simple phenylpropanoids that exerts beneficial effects on central nervous system. However, the effect of α-asarone on periphery is unexplored.Here, we investigated its protective role against depression from the aspect of KYN metabolism in skeletal muscle.The antidepressant effects of α-asarone were evaluated in chronic mild stress (CMS) and muscle-specific PGC-1α-deficient mice. The effects of KYN metabolism were determined in mice and C2C12 myoblasts.α-Asarone exerted antidepressant effects in CMS and KYN-challenged mice via modulating KYN metabolism. In myoblasts, α-asarone regulated PGC-1α induction via cAMP/CREB signaling and upregulated KYN aminotransferases (KATs) to increase KYN clearance in a manner dependent on PGC-1α. KAT function is coupled with malate-aspartate shuttle (MAS), while α-asarone combated oxidative stress to protect MAS and mitochondrial integrity by raising the NAD+ /NADH ratio, ensuring effective KYN disposal. In support, the antidepressant effect of α-asarone was diminished by muscle-specific PGC-1α deficient mice subjected to KYN challenge.KATs coupled with MAS to clear KYN in muscle. α-Asarone increased PGC-1α induction and promoted KYN disposal in muscle, suggesting that protection of mitochondria is a way for pharmacological intervention to depression." @default.
• W4313236411 created "2023-01-06" @default.
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• W4313236411 date "2022-12-27" @default.
• W4313236411 modified "2023-10-07" @default.
• W4313236411 title "<scp>Alpha‐Asarone</scp> modulates kynurenine disposal in muscle and mediates resilience to stress‐induced depression via <scp>PGC</scp>‐1α induction" @default.
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• W4313236411 doi "https://doi.org/10.1111/cns.14030" @default.
• W4313236411 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36575869" @default.
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