Ginsenoside Ro Ameliorates Cognitive Impairment and Neuroinflammation in APP/PS1 Mice via the IBA1/GFAP-MAPK Signaling Pathway

Tianyao Li ¹ Jiaxin Chen ¹ Zhouyuan Xie ¹ Jiansong Fang ¹ Qiqing Wu ¹ Xinyue Cao ¹ Ziying Chen ¹ Yiyun Wang ¹ Qiqi Fan ² Wang Qi ¹ Jinman Liu ^2*

• ¹ Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
• ² Jiangmen Wuyi Tranditional Chinese Medicine Hospital, Jiangmen, China

Ginseng, renowned as the "king of herbs," has been used in traditional Chinese medicine for centuries due to its anti-aging, anti-inflammatory, and anti-apoptotic properties. Ginsenosides, the active compounds in ginseng, have shown potential in treating neurodegenerative diseases, including Alzheimer's disease (AD). This study aimed to investigate the therapeutic potential and underlying mechanisms of Ginsenoside Ro in treating AD using the APP/PS1 transgenic mouse model. Male APP/PS1 transgenic mice were divided into five groups and treated with Ginsenoside Ro or ginseng for one month. Behavioral tests, such as the open field test (OFT) and Morris water maze (MWM), were conducted to assess cognitive function and anxiety. Thioflavin-T staining, Nissl staining, immunofluorescence, Western blot, and qRT-PCR analyses were performed to evaluate Aβ deposition, neuronal apoptosis, neuroinflammation, and the MAPK pathway. Ginsenoside Ro significantly improved cognitive function and reduced anxiety in APP/PS1 mice, decreased Aβ deposition, and ameliorated neuronal apoptosis in the cerebral cortex. The treatment modulated the expression of pro-apoptotic proteins Bax and Caspase3 and increased the anti-apoptotic protein Bcl-2. Ginsenoside Ro also reduced neuroinflammation by decreasing the activation of IBA1-positive microglia and GFAP-positive astrocytes and lowering pro-inflammatory cytokine levels while increasing anti-inflammatory cytokine IL-10. The phosphorylation levels of p38 and JNK in the MAPK pathway were significantly reduced, suggesting a key mechanism underlying the therapeutic effects. These findings support further investigation of Ginsenoside Ro as a potential therapeutic agent for AD, particularly through the modulation of the IBA1/GFAP-MAPK pathway.