Effect of Mahonia bealei Leaf Extract on Inflammation in Depression of Rats via NF-κB/NLRP3 Signaling Pathway / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo investigate the effect of Mahonia bealei leaf extract on depression of rats and the underlying mechanism. MethodThe chemical constituents of the extract were analyzed by HPLC-MS/MS. Forced swimming test and tail suspension test were carried out to estimate the antidepressant effect. The mice were randomly assigned into the following groups： blank group， positive control group （fluoxetine， 10 mg·kg-1）， and Mahonia bealei leaf extract groups （10， 2.5 g·kg-1）. The gavage lasted for 12 days and the immobility time of the mice in the tests was recorded 1 h after the last administration. Furthermore， to explore the underlying mechanism of the antidepressant effect， we established the rat depression model by intraperitoneal injection with reserpine （0.5 mg·kg-1）. Rats were grouped as follows： blank group， model group， positive control group （fluoxetine， 1.8 mg·kg-1）， and Mahonia bealei leaf extract groups （10， 2.5 g·kg-1）. The gavage， once a day， lasted for 10 consecutive days. The depression of rats was detected by behavioral tests 1 h after the last administration. The levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in serum of rats were detected by enzyme-linked immunosorbent assay （ELISA）. The protein expression of IL-6 and interleukin-1β （IL-1β） in brain tissue was detected by immunohistochemical staining. The protein levels of nuclear transcription factor-κB （NF-κB） and NOD-like receptor protein 3 （NLRP3） in hippocampus of rats were detected by Western blot. ResultSeven chemical constituents， mainly alkaloids， were identified from the extract. Compared with the blank group， Mahonia bealei leaf extract shortened the immobility time of mice in tail suspension and forced swimming tests. Compared with the blank group， the modeling of rat depression increased the blepharoptosis incidence and retention time in circles （P<0.05， P<0.01）， elevated the levels of IL-6 and TNF-α in serum （P<0.05）， and up-regulated the protein levels of IL-6， IL-1β， NF-κB， and NLRP3 in brain tissues （P<0.01）. Compared with the model group， high dose of Mahonia bealei leaf extract shortened the retention time in circles （P<0.05）， lowered the levels of IL-6 and TNF-α in serum （P<0.05， P<0.01）， and down-regulated the protein levels of IL-6， IL-1β， NF-κB， and NLRP3 （P<0.01） in brain tissues. ConclusionMahonia bealei leaf extract had significant antidepressant effect and alleviated the inflammatory response in reserpine-induced rat model of depression， the mechanism of which may be related to the inhibition of NF-κB/NLRP3 signaling pathway.