Chaihu-longgu-muli decoction exerts antidepressant effects in rats by regulating the NLRP3 pathway

Abstract

Introduction

Major Depressive Disorder (MDD) is becoming a highly prevalent psychosomatic disease worldwide, posing a serious threat to citizens' health. CNS inflammation is one of the important causes of MDD. Herbal medication Chaihu-Longgu-Muli Decoction (CLM) has antidepressant activity, but the mechanism is still unclear.

Methods

This study used CLM as a therapeutic drug and fluoxetine as a positive control to observe its behavioral, pathological, and molecular biological effects on CUMS depression model rats at different dose gradients. Practical LC-MS analysis was used to analyze its main components, and four pathological methods including HE, Nissl, IF, and TEM were used to observe neuropathological changes, polarization typing of microglia, and subcellular changes. WB and PCR were used to observe the molecular levels upstream and downstream of the NLRP3 pathway.

Results

The stimulation of CUMS causes inflammatory damage in hippocampus, excessive M1 polarization of microglia, and neuronal pyroptosis. The therapeutic effect of CLM is dose-dependent, and the neuroprotective effect of high-dose CLM is not inferior to that of fluoxetine. CLM promotes M2 polarization of microglia, reduces NLRP3 inflammasome synthesis, downregulates the NLRP3 pathway, thereby preventing neuronal pyroptosis and reducing the release of proinflammatory cytokine.

Discussion

CLM can give evidences in antidepression that downregulate the NLRP3 pathway, alleviate hippocampal inflammation and anti-pyroptosis. Further research is needed to verify the in vitro neuroprotective effect and control the inhibition of pyroptosis in enriching its antidepressant mechanism.