Acanthopanax Senticosus Saponins Prevent Cognitive Decline in Rats with Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a progressive degenerative disease of the nervous system that affects older adults. Its main clinical manifestations include memory loss, cognitive dysfunction, abnormal behaviour, and social dysfunction. Neuroinflammation is typical in most neurodegenerative diseases, such as AD. Therefore, suppressing inflammation may improve AD symptoms. This study investigated the neuroprotective effects of Acanthopanax senticosus saponins (ASS) in an AD model induced by streptozotocin (STZ). Here, we characterised a rat model of STZ-induced AD with the parallel deterioration of memory loss and neuroinflammation. Following the end of the treatment with ASS (50 mg/kg for 14 consecutive days), behavioural tests (Morris water maze test, Y-maze test) were performed on the rat, and the molecular parameters (DAPK1, Tau5, p-Tau, NF-κB, IL-1β, TNF-α, and NLRP3) of the rat hippocampus were also assessed. We demonstrated that ASS, which has potent anti-inflammatory effects, can reduce neuroinflammation and prevent cognitive impairment. In the water maze test, ASS-treated groups exhibited significantly increased average escape latency (p < 0.05), the percentage of stay in the target quadrant (p < 0.05), and the number of times each group of rats crossed the platform (p < 0.05) compared to the negative control. And ASS could reduce the phosphorylation of the Tau protein (p < 0.001) and death-associated protein kinase 1 (DAPK1, p < 0.001) in the hippocampal tissue, improving cognitive impairment in STZ-treated rats by suppressing the inflammatory response; the molecular analysis showed a significant reduction in pro-inflammatory markers like NLRP3, IL-1β, TNF-α, and NF-κB (p < 0.001). It was also discovered that the NF-κB inhibitor SN50 had the same effect. Therefore, the present study used ASS through its anti-inflammatory effects to prevent and treat AD. This study highlights the potential efficacy of ASS in alleviating cognitive dysfunction in AD.

Keywords: Acanthopanax senticosus saponins; Alzheimer’s disease; Tau protein; cognitive decline; inflammation.

Figure 1

Cognitive dysfunction in STZ-treated model rats. Morris water maze test and Y-maze test (n = 10/group). (A) Escape latency during the first 5 days; (B) Number of times the rats crossed the target quadrant; (C) Percentage of time in the target quadrant in both groups; (D) Representative swim paths in the test session on day 6. * p < 0.05, ** p < 0.01 compared with control); (E) Y-maze experiment alternating the correct rate of rats (** p < 0.01 compared with the control).

Figure 1

Cognitive dysfunction in STZ-treated model rats. Morris water maze test and Y-maze test (n = 10/group). (A) Escape latency during the first 5 days; (B) Number of times the rats crossed the target quadrant; (C) Percentage of time in the target quadrant in both groups; (D) Representative swim paths in the test session on day 6. * p < 0.05, ** p < 0.01 compared with control); (E) Y-maze experiment alternating the correct rate of rats (** p < 0.01 compared with the control).

Figure 2

Effect of ASS on the cognitive ability of STZ-treated rats. Morris water maze test and Y-maze test (n = 10/group). (A) Average escape latency in the first 5 days; (B) The number of times each group of rats crossed the platform; (C) The percentage of time in the target quadrant for each group of rats; (D) Representative trajectory maps of spatial exploration for each group of rats. * p < 0.05, ** p < 0.01 compared with the control group. # p < 0.05 compared with STZ-treated rats; (E) Y-maze experiment alternating the correct rate of rats (* p < 0.05 compared with the control group).

Figure 3

IF and HE staining of rat hippocampus in the CA3 areas. The number of neurons in the CA3 areas was reduced in the STZ-induced rat model of AD, and the number of neurons returned to normal after ASS treatment (n = 3).

Figure 4

Effect of ASS on the expression of pT231, pSer262, pSer396, and Tau5 in the hippocampal region of STZ-treated rats. (A–E) Expression of Tau5, pT231, pSer262, and pSer396 proteins in the hippocampal region (n = 5). **** p < 0.001 compared with the control group. ^#### p < 0.001 compared with the STZ + ASS group.

Figure 4

Effect of ASS on the expression of pT231, pSer262, pSer396, and Tau5 in the hippocampal region of STZ-treated rats. (A–E) Expression of Tau5, pT231, pSer262, and pSer396 proteins in the hippocampal region (n = 5). **** p < 0.001 compared with the control group. ^#### p < 0.001 compared with the STZ + ASS group.

Figure 5

Effect of ASS on the expression of DAPK1, NLRP3, NF-κB, lL-1β, and TNF-α protein in the hippocampal region of STZ-treated rats. (A–F) Expression of DAPK1, NLRP3, NF-κB, lL-1β, and TNF-α protein in the hippocampal region (n = 5)., *** p < 0.001, **** p < 0.0001 compared with the control group., ^## p < 0.01, ^### p < 0.001, ^#### p < 0.0001 compared with the STZ + ASS group.

Figure 5

Effect of ASS on the expression of DAPK1, NLRP3, NF-κB, lL-1β, and TNF-α protein in the hippocampal region of STZ-treated rats. (A–F) Expression of DAPK1, NLRP3, NF-κB, lL-1β, and TNF-α protein in the hippocampal region (n = 5)., *** p < 0.001, **** p < 0.0001 compared with the control group., ^## p < 0.01, ^### p < 0.001, ^#### p < 0.0001 compared with the STZ + ASS group.

Figure 6

Effects of NF-κB inhibitors on DAPK1 and phosphorylated Tau proteins. (A–D) Expression of NF-κB, DAPK1, and pS396 Tau proteins in the hippocampal region (n = 3). *** p < 0.001 compared with the control group. ### p < 0.001 compared with the SN50 group.

Figure 6

Effects of NF-κB inhibitors on DAPK1 and phosphorylated Tau proteins. (A–D) Expression of NF-κB, DAPK1, and pS396 Tau proteins in the hippocampal region (n = 3). *** p < 0.001 compared with the control group. ### p < 0.001 compared with the SN50 group.