Baihe Dihuangtang Improves Hippocampal Neuron Damage in Anxious Depression Model Rats by Inhibiting NLRP3 Inflammasome Activation / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the anti-anxious depression mechanism of Baihe Dihuangtang from the NOD-like receptor thermal protein domain 3 （NLRP3） inflammasome. Method:Fifty SD rats were randomly divided into normal group， model group， venlafaxine group （13.5 mg·kg^-1）， Baihe Dihuangtang high and low dose group （16，4 g·kg^-1）， with 10 rats in each group. Chronic restraint stress for 28 days （6 h） combined with subcutaneous injection of corticosterone （30 mg·kg^-1） was used to establish induce an anxious depression model. From the 8th day of modeling， the rats in the normal group and the model group received distilled water， and those in groups with drug intervention were treated with corresponding drugs by gavage for 21 days. Elevated plus maze and open field test were used to evaluate the behavioral changes of rats. Enzyme- linked immunosorbent assay （ELISA） was used to detect serum and hippocampal interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， interleukin-6 （IL-6） and interleukin-18 （IL-18） levels. Western blot were used to detect the relative expression of hippocampal NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， and Caspase-1. The pathological changes of the hippocampus were observed by hematoxylin-eosin（HE） staining， the average fluorescence intensity of NLRP3， ASC， and Caspase-1 was detected by immunofluorescence. The ultrastructure of neurons was observed under electron microscopy. Result:Compared with the normal group， the model group showed reduced total entries （TE）， the ratio of open-arm entries （OE%）， the ratio of open-arm times （OT%）， and the autonomous activity score （<italic>P</italic><0.01）， significant anxiety and depression-like behaviors， increased levels of IL-1<italic>β</italic>， IL-6， and IL-18 in the serum and hippocampus （<italic>P</italic><0.01）， elevated protein expression of NLRP3， ASC， and Caspase-1 （<italic>P</italic><0.01）， activated NLRP3 inflammasomes， and injured hippocampal neurons. Compared with the model group， the high-dose Baihe Dihuangtang group showed improved anxiety and depression-like behaviors （<italic>P</italic><0.01）， and decreased levels of IL-1<italic>β</italic>， IL-6， and IL-18 in the serum and hippocampus （<italic>P</italic><0.05，<italic>P</italic><0.01）， reduced protein expression of NLRP3， ASC， and Caspase-1 （<italic>P</italic><0.01）， and alleviated hippocampal neuron damage. Conclusion:Baihe Dihuangtang can improve neuronal damage in anxious depression by inhibiting the excessive activation of NLRP3 inflammasomes.