Effects of Dabugan Decoction on the improvement of generalized anxiety disorder in rats via ROS/Nrf2/HO-1 pathway
AIM To explore the mechanism of Dabugan Decoction's action on a rat model of generalized anxiety disorder(GAD).METHODS The rat models established by 21 days exposure to chronic unpredictable mild stress(CUMS)were then randomly divided into the model group,the paroxetine group(1.8 mg/kg)and the high-dose,medium-dose and low-dose Dabugan Decoction groups(13.2,6.6 and 3.3 g/kg),in contrast to the other normal rats assigned into the blank group,for the following 28 days administration of the corresponding drugs by gavage.After the intervention,the rats had their anxiety intensity analyzed by behavioral tests;their hippocampal pathological changes and Nissl's body differences observed by HE staining and Nissl staining;their cerebral ROS activity detected by immunofluorescence;their hippocampal activities of SOD and CAT,and levels of MDA and GSH detected by kit;and their hippocampal mRNA and protein expressions of Nrf2,Keap1,HO-1,NQO1,BDNF,5-HT1A,caspase-3 and GSH detected by RT-qPCR and Western blot.RESULTS Compared with the model group,the Dabugan Decoction groups displayed improved anxiety responses;increased movement distance at the open arm end and total distance as well,more entries and duration at the open box,more time and entries at the open field center in elevated plus maze(P＜0.05,P＜0.01);increased number of hippocampal neurons,ameliorated cell body damage,increased Nissl bodies in cells,decreased hippocampal ROS activity and MDA level(P＜0.05,P＜0.01);increased activities of SOD and CAT,and GSH level(P＜0.05,P＜0.01);increased hippocampal mRNA and protein expressions of Nrf2,HO-1,NQO1,BDNF and 5-HT1A(P＜0.05,P＜0.01),and decreased mRNA and protein expressions of p62,Keap1 and caspase-3(P＜0.05,P＜0.01).CONCLUSION Dabugan Decoction can effectively improve the anxiety of GAD rats,and its mechanism may be related to the recovery of oxidative stress-induced injury in hippocampal neurons via ROS/Nrf2/HO-1 signaling pathway.
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