Therapeutic effects of crude extracts of Bacopa floribunda on beta-amyloid 1-42-induced Alzheimer's disease via suppression of dyslipidemia, systemic inflammation and oxidative stress in male Wistar Rats

Abstract

Aims: Bacopa floribunda (BF), an African traditional plant and its species have been widely used as brain tonic for memory enhancement. It has also been reported to help relieve anxiety and some psychological disorders. This study aimed to investigate the mechanisms of action of BF on Amyloid beta (Aβ) 1-42 peptides induced cognitive deficit in male Wistar rats.

Main methods: A total of 48 healthy male wistar rats were used for this study. Some groups were pre-treated with 200 mg/kg of BF extracts before a single bilateral injection of Aβ 1-42 while some were post-treated with BF for 21 days after Aβ1-42 exposure. Cognitive performance was evaluated using Y-Maze and Novel Object recognition tests. After treatments, hippocampal homogenates were assayed for the levels of Acetylcholinesterase, Na-K/ATPase activities, glutamate and Aβ1-42 concentrations among others.

Key findings: It was observed that Aβ1-42 caused cognitive impairment and BF extracts especially the ethanol extract was able to significantly (p < 0.05) reverse almost all the perturbations including lipid imbalance caused by Aβ1-42 assault mainly at the post-treatment level.

Significance: Administration of ethanol and aqueous extracts of BF mitigated the hazardous effect of Aβ1-42 observed in the blood plasma and hippocampal homogenates. In this context, we conclude that BF is an efficient cognitive enhancer that can help alleviate some symptoms associated with Alzheimer's disease.

Keywords: Acetylcholinesterase; Bacopa floribunda; Cognitive enhancer; Glutamate excitotoxicity; Na–K/ATPase.

Graphical abstract

Figure 1

Flowchart of BF extraction, Invito assays and animal grouping for invivo experiments

Figure 2

Showing the different invitro antioxidant assays at various concentrations at a significant level of p < 0.05; (a) DPPH Radical Scavenging Ability of Ethanol Extract {# (p = 0.0213), ##(p = 0.0014), ### (p = 0.0001), #### (p < 0.0001)}, (b) DPPH Radical Scavenging Ability of Aqueous Extract {# (p < 0.05), ##(p < 0.005)}, (c) Comparison of DPPH Radical Scavenging Ability of both Aqueous and Ethanol Extract {∗ (p < 0.05) observed at all concentrations} and (d) ABTS Radical Scavenging Ability of both Aqueous and Ethanol Extract {∗ (p < 0.05)}.

Figure 3

Effect of treatment on (a) Memory index as recorded during the NOR test. (b) Spontaneous alternation of rats. The following symbols signify the levels of significance at p < 0.05 across groups, using ANOVA and Tukey’s posthoc test, γ = significantly different from N/S, δ = significantly different from Aβ, η = significantly different from AEBF + Aβ, ε = significantly different from Aβ+AEBF.

Figure 4

Effect of treatments on hippocampal acetylcholinesterase level. The following symbols signify the levels of significance at p < 0.05 across groups, using ANOVA and Tukey’s posthoc test, γ = significantly different from N/S, δ = significantly different from A/β, ε = significantly different from AEBF + Aβ.

Figure 5

Showing the levels of some antioxidant markers and product of lipid peroxidation in the hippocampus and blood; (a) Hippocampal Glutathione peroxidase (GPx) level, (b) Reduced glutathione (GSH) level in the blood, (c) Hippocampal Malondialdehyde (MDA) concentration and (d) MDA conc. in the blood. The following symbols signify the levels of significance at p < 0.05 across groups, using ANOVA and Tukey’s posthoc test, # = significantly different from groups C, D and E, ∗∗∗ = significantly different from all groups; γ = sig diff from N/S, δ = sig diff from Aβ, ε = sig diff from EEBF Alone, η = sig diff from AEBF Alone, and ρ = significantly different from EEBF + Aβ.

Figure 6

C-Reactive Protein (CRP) concentration as measured in the blood after the different treatment regimen. The following symbols depict a level of significance at p < 0.05 across groups; γ = sig diff from N/S, δ = sig diff from EEBF Alone, ε = sig diff from AEBF Alone, ∞ = sig diff from EEBF + Aβ, ρ = sig diff from Aβ+EEBF and σ = sig diff from Aβ+AEBF.

Figure 7

Effect of treatment on (a) hippocampal Na⁺/K⁺-ATPase (b) hippocampal glutamate concentration of rats in each group after different treatment interventions. The following symbols signify the levels of significance at p < 0.05 across groups, using ANOVA and Tukey’s posthoc test, γ = significantly different from N/S, ε = significantly different from EEBF alone, η = significantly different from AEBF alone, # = significantly different from groups D (AEBF alone), E (EEBF + Aβ) and F (AEBF + Aβ).

Figure 8

Showing the levels of blood lipid profiles in mg/dL; (a) Total cholesterol (TC), (b) Triglyceride (TG), (c) High Density Lipoprotein (HDL) and (d) Low Density Lipoprotein (LDL). The following symbols signify the levels of significance at p < 0.05 across groups, using ANOVA and Tukey’s posthoc test, ∗∗∗ = significantly different from all groups; γ = sig diff from N/S, δ = sig diff from EEBF Alone, ε = sig diff from AEBF Alone, η = sig diff from AEBF + Aβ, ρ = sig diff from Aβ+EEBF and σ = sig diff from Aβ+AEBF.

Figure 9

Effect of treatments on hippocampal Aβ level. The following symbols signify the levels of significance at p < 0.05 across groups, using ANOVA and Tukey’s posthoc test, γ = significantly different from N/S, δ = significantly different from A/β.

Figure 10

Effect of treatments on the dentate gyrus and CA3 of the hippocampus of experimental animals. This revealed the presence of granule cells in the granular layer and some pyramidal neurons in the molecular layer in the vehicle and extract control groups. These were not prominent in the untreated group as the cells became degenerated while the degeneration was prevented in the post treated models, it was mildly preserved in the pre-treated model.