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        Corydalis yanhusuo Polysaccharides Ameliorate Chronic Stress-Induced Depression in Mice through Gut Microbiota-Derived Short-Chain Fatty Acid Activation of 5-Hydroxytryptamine Signaling

        Yu Fang,Yanqing Li,Xin Liao,Jie Deng,Qiannan Wang,Jingtao Liang,Bohua Yan 한국식품영양과학회 2023 Journal of medicinal food Vol.26 No.12

        Depression, a prevalent psychiatric disorder, presents a serious health risk to humans. Increasing evidencesuggested that the gut microbiota and the 5-hydroxytryptamine (5-HT) pathway both contribute significantly to depression. This research aimed to investigate how Corydalis yanhusuo polysaccharides (CYP) could potentially alleviate depressioninduced by chronic unpredictable mild stress in mice, as well as its underlying mechanism. The sucrose preference test, tailsuspension test, and forced swimming test were employed to evaluate the behavior of mice. Enzyme-linked immunosorbentassay and PCR techniques were utilized to measure depression-related factors (dopamine [DA], 5-HT, norepinephrine [NE],brain-derived neurotrophic factor [BDNF], tryptophan hydroxylase 2 [TPH-2], 5-hydroxytryptophan [5-HTP], and tryptophanhydroxylase [TPH-1] levels). Hematoxylin and eosin staining and Nissl staining were conducted to observe histopathologicalchanges in the hippocampus, the differences in the diversity of gut flora between groups were analyzed using 16S rRNAsequencing, and gas chromatography–mass spectrometry metabolomics was utilized to evaluate short-chain fatty acid (SCFA)concentrations. The findings indicated that CYP treatment increased the sucrose preference index, decreased the immobilitytime, and improved neuropathological injury. In depressed mice, CYP improved the dysregulation of the gut microbiota, andincreased the SCFA levels. In addition, CYP enhanced the DA, 5-HT, NE, BDNF, and TPH-2 levels in the brain and theexpression of 5-HTP and TPH-1 in the colon, while SCFAs were positively correlated with these levels. In summary, ourstudy suggested that CYP may mitigate depression by ameliorating gut microbiota dysregulation, promoting the generation ofSCFAs, and activation of 5-HT signaling expression.

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