2. Academic Validation
  3. Microbiota basis of antidepressant effects of Zhi-zi-chi Decoction: Lactobacillus rhamnosus and gut microbiota metabolism

Microbiota basis of antidepressant effects of Zhi-zi-chi Decoction: Lactobacillus rhamnosus and gut microbiota metabolism

  • Chin Herb Med. 2025 May 9;17(4):798-807. doi: 10.1016/j.chmed.2025.05.001.
Jing He 1 2,  Zixin Zhao 1 2,  Ying Ye 1 2,  Yujia Zhai 3,  Dexun Yu 1 2,  Fangyuan Gao 4,  Jianlin Wu 5,  Jun Wen 1 2,  Tingting Zhou 1 2
Affiliations

Affiliations

  • 1 School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
  • 2 Shanghai Key Laboratory of Pharmaceutical Metabolite Research, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
  • 3 Naval Medical Center, Second Military Medical University, Shanghai 200433, China.
  • 4 Department of Health Toxicology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China.
  • 5 State key laboratory of mechanism and quality of Chinese medicine, Macau University of Science and Technology, Taipa, Macau SAR, 999078, China.
PMID: 41399797 DOI: 10.1016/j.chmed.2025.05.001
Abstract

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.

Keywords

Lactobacillus rhamnosus; Zhi-zi-chi Decoction; antidepressant effects; metabolites; microbial bases.

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