Mechanism of Bugansan Decoction in ameliorating learning and memory impairment in D-galactose-induced aging rats based on AGEs/RAGE/NF-κB pathway
10.1016/j.dcmed.2023.10.007
- Author:
Wei LI
1
;
Shuo WANG
1
;
Jiepeng WANG
2
;
Fang FANG
2
;
Chaoyi FANG
2
Author Information
1. School of Preclinical Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, China
2. School of Preclinical Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, China/Hebei Key Laboratory of Integrated Chinese and Western Medicine for Lung Disease Research, Shijiazhuang, Hebei 050091, China
- Publication Type:Journal Article
- Keywords:
Bugansan Decoction (补肝散, BGSD), Liver Qi deficiency, Aging, Learning and memory, Neuroinflammation, AGEs/RAGE/NF-κB signaling pathway
- From:
Digital Chinese Medicine
2023;6(3):317-327
- CountryChina
- Language:English
-
Abstract:
Objective To investigate the underlying mechanism of the compound Bugansan Decoction
(补肝散, BGSD) in intervening learning and memory in D-galactose (D-gal)-induced aging rats.
Methods:A total of 40 rats were randomly assigned to four groups: control, model, BGSD [14.06 g/(kg·d)], and piracetam [0.4 g/(kg·d)] groups, with 10 rats in each group. D-gal [400 mg/(kg·d)] was injected intraperitoneally to establish the aging rat model. The rats' body weight, water intake, food intake, and gripping strength were recorded each week. The eightarm maze and step-down test were used to measure the rats' capacity for learning and memory. Liver, thymus, spleen, and brain tissues were weighed to calculate the corresponding organ indices; serum malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured. Hematoxylin and eosin (HE) staining was adopted to observe the pathological changes of the hippocampus; enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the hippocampus. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of receptors for advanced glycation end products (RAGE), nuclear factor-κB (NF-κB), TNF-α, IL-6, and IL-1β mRNA in the hippocampus. Western blot (WB) was employed to detect the expression levels of advanced glycation end products (AGEs), RAGE, and NF-κB protein in the hippocampus.
Results:In D-gal-induced aging rats, BGSD significantly increased food intake, water intake, body weight, gripping strength, and organ indices (P < 0.05), and significantly decreased working memory error (WME), reference memory error (RME), and total memory errors (TE) in an eight-arm maze (P < 0.05). In the step-down test, step-down latency was prolonged and the frequency of errors dropped (P < 0.05). Additionally, BGSD could lessen the harm done to hippocampus neurons, increase serum SOD activity, lower MDA levels, and down-regulate the expression levels of the pro-inflammatory molecules TNF-α, IL-6, and IL-1β (P < 0.05). Further findings showed that BGSD significantly decreased hippocampal AGEs, RAGE, and NF-κB expression (P < 0.05).
Conclusion:By blocking the AGEs/RAGE/NF-κB signaling pathway, BGSD may regulate the neuroinflammatory damage in D-gal-induced aging rats, and thus improve learning and memory.
- Full text:liwei2023.pdf
