Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Feb;13(2):413-420.
doi: 10.3892/etm.2016.4004. Epub 2016 Dec 27.

Asiaticoside ameliorates β-amyloid-induced learning and memory deficits in rats by inhibiting mitochondrial apoptosis and reducing inflammatory factors

Zhuo Zhang  1 , Xiaobin Li  1 , Duo Li  2 , Mao Luo  3 , Yongjie Li  3 , Li Song  4 , Xian Jiang  4
Affiliations

Asiaticoside ameliorates β-amyloid-induced learning and memory deficits in rats by inhibiting mitochondrial apoptosis and reducing inflammatory factors

Zhuo Zhang et al. Exp Ther Med. 2017 Feb.

Abstract

The present study aimed to investigate the effects of asiaticoside (AS) on the pathology and associated mechanisms of β-amyloid (Aβ)-induced Alzheimer's disease (AD) in rats. An AD rat model was established by lateral intracerebroventricular injection of Aβ 1-42 oligomers. Learning and memory function were evaluated by Morris water maze (MWM) test. In addition, hematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), immunohistochemistry, ELISA and western blot analysis were performed to evaluate the disease pathogenesis. The results indicated that AS exerted protective effects in rats treated with Aβ oligomers, in a dose-dependent manner, as evidenced by the improved learning and memory function in the MWM test. In addition, H&E staining of hippocampal tissue showed that the histological structure was damaged in the model group, which was restored by AS treatment. Aβ deposition was dramatically increased in the model group, and the pathological changes were reversed by AS treatment. TEM revealed that the subcellular structure was injured by Aβ oligomers, however, the structure was ameliorated by AS treatment. Furthermore, AS was found to reduce the elevated levels of pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-α, in the brains of Aβ-treated rats. In addition, AS treatment resulted in a significant decrease in the expression of caspases-3, whereas the expression of B-cell lymphoma-2 was significantly increased, in these Aβ-treated rats. According to the findings of the observed study, AS has a marked protective effect on Aβ-induced AD pathology, and the underlying mechanism may be associated with the alleviation of the mitochondrial injuries, the anti-inflammatory activities, and the influence on the expression levels of apoptosis-associated proteins.

Keywords: B-cell lymphoma-2; anti-inflammatory; asiaticoside; caspase-3; β-amyloid.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
AS treatment ameliorated the learning and memory deficit in Aβ-treated rats. Morris water maze test was performed for 5 days to assess the learning and memory function of Aβ-treated rats. The (A) escape latency, (B) swimming time in the target quadrant, and (C) navigation path in the various study groups are shown. #P<0.05 and ##P<0.01, vs. control group. AS, asiaticoside; Aβ, β-amyloid
Figure 2.
Figure 2.
AS treatment restored the impaired histological structure in rats treated with β-amyloid. Hematoxylin and eosin staining was performed to detect the histological structure of the hippocampus of rats in the control, sham, model and AS treatment (5, 15 or 45 mg/kg body weight) groups. Scale bar, 10 µm. AS, asiaticoside.
Figure 3.
Figure 3.
AS treatment decreased Aβ deposition in hippocampus in Aβ-treated rats. Immunohistochemical analysis was performed to detect the Aβ deposition in hippocampus in the control, sham, model and AS treatment (5, 15 or 45 mg/kg body weight) groups. Arrows indicated neuritic plaques. Scale bar, 10 µm. AS, asiaticoside; Aβ, β-amyloid.
Figure 4.
Figure 4.
AS treatment ameliorated the impaired subcellular structure in the brains of Aβ-treated rats. Transmission electron microscopy was performed to detect the Aβ deposition in the hippocampus of rats in the control, sham, model and AS treatment (5, 15 or 45 mg/kg body weight) groups. Scale bar, 2 µm. AS, asiaticoside; Aβ, β-amyloid.
Figure 5.
Figure 5.
AS treatment reduced the levels of the pro-inflammatory cytokines (A) IL-6 and (B) TNF-α in the brains of Aβ-treated rats. The levels in the brain dialysate were measured by enzyme-linked immunosorbent assay. #P<0.05 and ##P<0.01 vs. control group; *P<0.05 and **P<0.01, vs. model group. AS, asiaticoside; IL-6, interleukin-6; TNF, tumor necrosis factor; Aβ, β-amyloid.
Figure 6.
Figure 6.
AS treatment decreased caspase-3 expression and increased Bcl-2 expression in Aβ-treated rats. (A) The expression levels of caspase-3 and Bcl-2 in the hippocampus were detected by western blot analysis. Statistical analysis graphs of the expression levels of (B) caspase-3 and (C) Bcl-2 are shown. ##P<0.01 vs. control group; *P<0.05 and **P<0.01, vs. model group. AS, asiaticoside; Bcl-2, B-cell lymphoma-2; Aβ, β-amyloid.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Qi FY, Yang L, Tian Z, Zhao MG, Liu SB, An JZ. Neuroprotective effects of Asiaticoside. Neural Regen Res. 2014;9:1275–1282. doi: 10.4103/1673-5374.137574. - DOI - PMC - PubMed
    1. Zhang Zhuo, Liu Minghua, Zhang Hong, Wu Jianbo, Wan Jinyuan. Effects of Aisaticoside on Apoptosis of PC12 cells Induced by β-amylnid Peptide. Chinese Journal of New Drugs. 2012;21:206–210.
    1. Zhang L, Li HZ, Gong X, Luo FL, Wang B, Hu N, Wang CD, Zhang Z, Wan JY. Protective effects of Asiaticoside on acute liver injury induced by lipopolysaccharide/D-galactosamine in mice. Phytomedicine. 2010;17:811–819. doi: 10.1016/j.phymed.2010.01.008. - DOI - PubMed
    1. Miklossy J, Kis A, Radenovic A, Miller L, Forro L, Martins R, Reiss K, Darbinian N, Darekar P, Mihaly L, Khalili K. Beta-amyloid deposition and Alzheimer's type changes induced by Borrelia spirochetes. Neurobiol Aging. 2006;27:228–236. doi: 10.1016/j.neurobiolaging.2005.01.018. - DOI - PubMed
    1. Tomic JL, Pensalfini A, Head E, Glabe CG. Soluble fibrillar oligomer levels are elevated in Alzheimer's disease brain and correlate with cognitive dysfunction. Neurobiol Dis. 2009;35:352–358. doi: 10.1016/j.nbd.2009.05.024. - DOI - PMC - PubMed