Regulation of the kynurenine/serotonin pathway by berberine and the underlying effect in the hippocampus of the chronic unpredictable mild stress mice

小檗碱对犬尿氨酸/血清素通路的调节及其对慢性不可预测轻度应激小鼠海马的影响

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作者:Qi Wang, Ya-Nan Sun, Chun-Ming Zou, Te-Li Zhang, Zhu Li, Min Liu, Bi-Ying Shi, Shan-Shan Shi, Chun-Yue Yu, Tai-Ming Wei

Background

Depression is a common mental disorder and is one of the main causes of disability. Berberine (BBR), the major constituent alkaloid originally from the famous Chinese herb Huanglian (Coptis chinensis), has been shown to exert antidepressant-like effects. This study was to investigate the hypothesis that BBR treats depressive-like behavior by shifting the balance of the kynurenine (KYN)/serotonin (5-HT) pathway toward the 5-HT pathway through downregulated indoleamine 2,3-dioxygenase 1 (IDO1), monoamine oxidase A (MAOA) and upregulated dopamine decarboxylase (DDC) in hippocampus. Method: A chronic unpredictable mild stress (CUMS) mice model of depression was established via 21 days unpredictable stimulation. Then the mice were randomly assigned into six groups, namely control, model, fluoxetine [FLU, (10 mg/kg)], BBRL (25 mg/kg), BBRM (50 mg/kg), and BBRH (100 mg/kg) groups. Behavioral assessments were conducted to evaluate the antidepressant effects of BBR. The levels of 5-HT, KYN, tryptophan (TRP), and 5-hydroxyindoleacetic acid (5-HIAA) in hippocampus were estimated using high performance liquid chromatography (HPLC). The mRNA and protein levels of DDC, MAOA and IDO1 in hippocampus were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and western blot (WB), respectively. Result: The

Conclusions

BBR reversed the abnormalities of the KYN/5-HT pathway in depressed mice and achieved an excellent antidepressant effect. Its direct impact may be observed as changes in biological indicators in mice hippocampus tissue.

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