Effect of Gouteng Jiangya Jieyu Prescription on Neuronal Damage in Rats With Hypertension Complicated by Depression via ROS/AKT/NF-κB Pathway

Shan Gong, Yeqian Liu, Chunming Chen, Min Feng, Meiqi Yang, Weiqiong Ren

https://doi.org/10.1002/pul2.70306 

Abstract

Gouteng Jiangya Jieyu Prescription (GTJYJYP) shows potential in regulating blood pressure and improving mood. This study aims to investigate GTJYJYP's neuroprotective effects against neuronal damage and its underlying mechanisms in rats with hypertension complicated by depression (HD). Forty-eight male SHR were randomly divided into SHR group, HD group, GTJYJYP low-dose (6.34 g/kg), medium-dose (12.69 g/kg), high-dose group (25.38 g/kg), and a positive control group. And eight WKY rats were served as the control group. Blood pressure, depressive-like behaviors and the contents of ROS, GSH, MDA TNF-α, IL-1β, IL-6, and IL-18 were measured. Hippocampal neuronal morphology was observed using HE and Nissl staining. Protein expression of ROS/AKT/NF-κB pathway was detected by WB. Subsequently, ROS inducer H2O2 and AKT inhibitor MK2206 were used for intervention, and the changes of the above indicators were observed. Compared to the control group, blood pressure in both SHR and HD group rats was significantly elevated. Compared to the control and SHR groups, rats in HD group exhibited depressive-like behavior significantly. Furthermore, the HD group showed elevated levels of TNF-α, IL-1β, IL-6, IL-18, ROS, and MDA, along with reduced GSH levels significantly. Besides, the ratios of p-NF-κB p65/NF-κB p65 and p-AKT/AKT in HD group were increased significantly. Obvious neuronal damage was observed by Nissl staining. After the treatment of different doses of GTJYJYP and the positive drug, the damage was ameliorated. The ROS/AKT/NF-κB pathway was significantly inhibited. H₂O₂ treatment reversed the protective effects of GTJYJYP, whereas MK2206 further enhanced the ameliorative effects of GTJYJYP on oxidative stress, inflammatory response, and neuronal damage. GTJYJYP ameliorates neuronal damage in rats with HD through ROS/AKT/NF-κB pathway.

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