Suanzaoren decoction improves depressive-like behaviors by regulating the microbiota-gut-brain axis via inhibiting TLR4/NFκB/NLRP3 inflammation signal pathway

Yiyang Du; Bosai He; Bo Wu; Tingxu Yan; Ying Jia

doi:10.1016/j.jchemneu.2023.102349

Suanzaoren decoction improves depressive-like behaviors by regulating the microbiota-gut-brain axis via inhibiting TLR4/NFκB/NLRP3 inflammation signal pathway

J Chem Neuroanat. 2023 Dec:134:102349. doi: 10.1016/j.jchemneu.2023.102349. Epub 2023 Oct 23.

Authors

Yiyang Du¹, Bosai He¹, Bo Wu¹, Tingxu Yan², Ying Jia³

Affiliations

¹ School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China.
² School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: yantingxu@126.com.
³ School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: jysyphu@126.com.

PMID: 37879571
DOI: 10.1016/j.jchemneu.2023.102349

Abstract

Depression is a common but serious sickness which causes a considerable burden on individuals and society. Recently, it has been well established that the occurrence of depression was related to the microbiota-gut-brain axis. The toll-like receptor 4 (TLR4)/ nuclear factor kappa-B kinase (NFκB)/ NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway is closely associated with the regulation of microbiota-gut-brain axis. Suanzaoren Decoction (SZRD), which recorded in Jin Gui Yao Lve in Han dynasty, has been used for treating insomnia and depression for a long time. However, the action mechanism of the depression regulation through the TLR4/NFκB/NLRP3 pathway by SZRD was still unclear. In this study, SZRD was firstly performed on a chronic unpredictable mild stress (CUMS) mice model. The results of behavioral tests showed that SZRD treatment could ameliorate the depressive-like behaviors of CUMS mice effectively. According to our previous researches about the components of SZRD in vitro and in vivo, the identification of serum metabolites in depression model rats was further analyzed qualitatively using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. 27 prototypes and 44 metabolites were identified. The main types of metabolic reactions are glucuronization, sulfation, and so on. Then, using immunohistochemistry and western blotting to monitor the difference in activation of TLR4/NFκB/NLRP3 signaling pathway in mice brain and colon. The results showed that SZRD treatment could reduce expression levels of related factors. Additionally, the SZRD treatment could also inhibit the histopathological damage in the path morphology of the hippocampus and colon. The results of 16SrRNA demonstrated that SZRD could reduce the dysbiosis of the intestinal flora of depressive mice. The above results provided important information for studying the action mechanism of SZRD in treating depression by regulating microbiota-gut-brain axis via inhibiting TLR4/NFκB/NLRP3 pathway.

Keywords: Depression; Microbiota-gut-brain axis; Serum components; Suanzaoren Decoction; TLR4/NFκB/NLRP3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain-Gut Axis* / drug effects
Depression / drug therapy
Depression / etiology
Inflammation / metabolism
Mice
NF-kappa B / drug effects
NF-kappa B / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein* / drug effects
NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
Rats
Signal Transduction
Toll-Like Receptor 4* / drug effects
Toll-Like Receptor 4* / metabolism

Substances

NLR Family, Pyrin Domain-Containing 3 Protein
suanzaoren
Toll-Like Receptor 4
NF-kappa B