Botanical Drug Puerarin Ameliorates Liposaccharide-Induced Depressive Behaviors in Mice via Inhibiting RagA/mTOR/p70S6K Pathways

Author:

Zhao Jia1234ORCID,Jia Yizhen1,Zhao Wei2ORCID,Chen Huixin2,Zhang Xiuying2,Ngo Fung Yin2,Luo Dan2,Song Youqiang5ORCID,Lao Lixing2ORCID,Rong Jianhui26ORCID

Affiliation:

1. Department of Chinese Medicine, The University of Hong Kong Shenzhen Hospital, Shenzhen, China

2. School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China

3. Zhu Nansun’s Workstation, School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China

4. Yu Jin’s Workstation, School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China

5. School of Biomedical Science, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China

6. The University of Hong Kong Shenzhen Institute of Research and Innovation (HKU-SIRI), Shenzhen, China

Abstract

Background. The depressive symptom hallmarks the progression of the neurodegenerative diseases, especially Alzheimer’s disease. Bacterial infection is related to inflammation and depression. The present project thereby examined whether botanical drug puerarin could attenuate liposaccharide- (LPS-) induced depressive behaviors in mice. Methods. Adult male C57BL/6N mice were sequentially treated with LPS and puerarin and evaluated for the depressive behaviors by tail suspension test and forced swim test. The brain tissues were profiled for the molecular targets of puerarin by next-generation RNA sequencing technique. Candidate targets were further verified in LPS-treated mice, neural stem cells, and highly differentiated PC12 cell line. Results. Puerarin ameliorated LPS-induced depression in the mice. RNA sequencing profiles revealed that puerarin altered the expression of 16 genes while markedly downregulated Ras-related GTP-binding protein A (RagA) in LPS-treated mice. The effect of puerarin on RagA expression was confirmed by immunostaining, Western blot, and quantitative real-time PCR (qRT-PCR). Biochemical studies showed that puerarin inhibited RagA/mTOR/p70S6K pathway, attenuated the accumulation of mTORC1 in close proximity to lysosome, and reduced the production of proinflammatory cytokines. Conclusions. Botanical drug puerarin attenuated inflammation and depressive behaviors in LPS-challenged mice by inhibiting RagA/mTOR/p70S6K pathways. Puerarin may be a lead compound for the new antidepressant drugs.

Funder

Midstream Research Programme for Universities

Publisher

Hindawi Limited

Subject

Cell Biology,Ageing,General Medicine,Biochemistry

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