Objective: Zhi-zi-chi Decoction (ZZCD) is a classical antidepressant traditional Chinese medicine (TCM) formula. However, the microbiological basis of its antidepressant effects remains unclear. The objective of this study was to investigate the microbial basis of ZZCD. Methods: The bacteria that exhibit enhanced growth in ZZCD extracts were identified through in vitro culture. A depressed rat model was subsequently established to assess the antidepressant effects of the bacteria. A GC–MS-based metabolomics approach and molecular docking simulation were employed to investigate the potential mechanism of the antidepressant effects of the bacteria from the perspective of changes in the metabolic profile of the gut microbiota. Finally, the antioxidant effects of gut microbial metabolites following Lactobacillus rhamnosus treatment were validated through cellular experimentation. Results: ZZCD was able to promote the growth of L. rhamnosus. Furthermore, L. rhamnosus was demonstrated to increase the percentage of sucrose preference, reduce the immobility time in tail suspension and forced swimming tests, and alleviate depressive symptoms in rats. Additionally, L. rhamnosus was shown to alter the metabolic profile of gut microbiota. A total of six metabolites (ethanamin, butyric acid, 2-methylbutanoic acid, behenic acid, 3-methylvaleric acid and 1-hexadecanol) associated with depressive behavior in rats were identified. All six metabolites demonstrated the capacity to bind to kelch-like ECH-associated protein 1 (Keap 1) in molecular docking simulations. Gut microbial metabolites after L. rhamnosus treatment increased nuclear factor erythroid 2-related factor 2 (Nrf2) levels in HT22 cells. Conclusion: L. rhamnosus may be one of the microbial bases for the antidepressant effects of ZZCD. Its effects may be related to the regulation of gut microbiota metabolism and anti-oxidative stress.
关键词:
抗抑郁效果;鼠李糖乳杆菌;代谢产物;微生物基础;栀子豉汤
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This work was supported by the Funds for International Cooperation and Exchange of the National Natual Science Foundation of China (No. 82461160264), the National Natural Science Foundation of China (No. 82474056, 81973457, 81573584), and the grant from Science and Technology Commission of Shanghai Municipality (No. 21S21902400), Shanghai Municipal Health Commission (No. 2022XD037), Shanghai Magnolia Talent Plan Pujiang Project (No. 23PJD113), the National Science and Technology Major Project of the Ministry of Science and Technology of China (No. 2023ZD502605), and the Science and Technology Development Fund, Macau SAR (No. 0151/2024/AFJ). We extend our gratitude to the National Demonstration Center for Experimental Nautical Medicine Education, Naval Medical University, for their support.
