Astragalosides attenuate learning and memory impairment in rats following ischemia‑reperfusion injury

Wu,Yang‑Yang; Wu,Wang‑Yang; Gong,Hui‑Ling; Li,Wei‑Zu; Yin,Yan‑Yan

doi:10.3892/mmr.2014.1969

Astragalosides attenuate learning and memory impairment in rats following ischemia‑reperfusion injury

Authors:
- Yang‑Yang Wu
- Wang‑Yang Wu
- Hui‑Ling Gong
- Wei‑Zu Li
- Yan‑Yan Yin
View Affiliations

Affiliations: Department of Pharmacology, Anhui Medical University, Key Laboratory of Chinese Medicine Research and Development, State Administration of Traditional Chinese Medicine, Hefei, Anhui 230032, P.R. China
Published online on: February 19, 2014 https://doi.org/10.3892/mmr.2014.1969
Pages: 1319-1324

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Astragalosides (ASTs) have been traditionally used in the treatment of various cardiovascular and cerebrovascular diseases. The aim of the present study was to investigate the neuroprotective effects of AST on learning and memory following focal cerebral ischemia/reperfusion in a rat model. A Morris water maze was used to measure the effect of AST on learning and memory impairments. A histological examination and Hoechst 33258 staining was used to observe the neuronal changes and apoptosis in the hippocampus. The activity of phospho-extracellular signal‑regulated kinases (p‑ERK), p‑c-Jun N-terminal kinases (JNK) and p‑Akt was measured by western blotting. The data revealed that AST improved the rats learning and memory abilities, attenuated neuronal cells apoptosis, increased the expression of p‑ERK and p‑Akt, and decreased the expression of p‑JNK. These findings indicated that AST has protective effects that may be correlated with the inhibition of neuronal cell apoptosis and the regulation of p‑ERK, p‑Akt and p‑JNK expression.

View Figures

View References

1	Hattori K, Lee H, Hurn PD, Crain BJ, Traystman RJ and DeVries AC: Cognitive deficits after focal cerebral ischemia in mice. Stroke. 31:1939–1944. 2000. View Article : Google Scholar : PubMed/NCBI
2	Bouët V, Freret T, Toutain J, Divoux D, Boulouard M and Schumann-Bard P: Sensorimotor and cognitive deficits after transient middle cerebral artery occlusion in the mouse. Exp Neurol. 203:555–567. 2007.PubMed/NCBI
3	Shioda N, Han F, Morioka M and Fukunaga K: Bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) enhances neurogenesis via phosphatidylinositol 3-kinase/Akt and extracellular signal regulated kinase activation in the hippocampal subgranular zone after mouse focal cerebral ischemia. Neuroscience. 155:876–887. 2008. View Article : Google Scholar
4	Lee TH, Kato H, Chen ST, Kogure K and Itoyama Y: Expression of nerve growth factor and trkA after transient focal cerebral ischemia in rats. Stroke. 29:1687–1697. 1998. View Article : Google Scholar : PubMed/NCBI
5	Irving EA and Bamford M: Role of mitogen- and stress-activated kinases in ischemic injury. J Cereb Blood Flow Metab. 22:631–647. 2002. View Article : Google Scholar : PubMed/NCBI
6	Zhao H, Shimohata T, Wang JQ, Sun G, Schaal DW, Sapolsky RM and Steinberg GK: Akt contributes to neuroprotection by hypothermia against cerebral ischemia in rats. J Neurosci. 25:9794–9806. 2005. View Article : Google Scholar : PubMed/NCBI
7	Yin YY, Li WP, Gong HL, Zhu FF, Li WZ and Wu GC: Protective effect of astragaloside on focal cerebral ischemia/reperfusion injury in rats. Am J Chin Med. 38:517–527. 2010. View Article : Google Scholar : PubMed/NCBI
8	Yin YY, Li WP, Li WZ, Gong HL, Zhu FF and Wu GC: Effects of astragalosides on the expression of BDNF, TrkB and p75NTR mRNA against focal cerebral ischemia-reperfusion injury. Chinese Pharmacological Bulletin. 25:672–676. 2009.
9	Li W, Li W, Yin Y, Gong H, Wu G and Zhu F: Protective effects of AST and ASI on memory impairment and its mechanism in senescent rats treated by GC. Zhongguo Zhong Yao Za Zhi. 34:199–203. 2009.(In Chinese).
10	Longa EZ, Weinstein PR, Carlson S and Cummins R: Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 20:84–91. 1989. View Article : Google Scholar : PubMed/NCBI
11	Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL and Bartkowski H: Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke. 17:472–476. 1986. View Article : Google Scholar : PubMed/NCBI
12	Wiard RP, Dickerson MC, Beek O, Norton R and Cooper BR: Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia. Stroke. 26:466–472. 1995. View Article : Google Scholar : PubMed/NCBI
13	Li WZ, Li WP, Zhang W, Yin YY, Sun XX, Zhou SS, Xu XQ and Tao CR: Protective effect of extract of Astragalus on learning and memory impairments and neurons’ apoptosis induced by glucocorticoids in 12-month-old male mice. Anat Rec (Hoboken). 294:1003–1014. 2011.PubMed/NCBI
14	Kim SJ, Yoo KY, Jeong CW, Kim WM, Lee HK, Bae HB, Kwak SH, Li M and Lee J: Urinary trypsin inhibitors afford cardioprotective effects through activation of PI3K-Akt and ERK signal transduction and inhibition of p38 MAPK and JNK. Cardiology. 114:264–270. 2009. View Article : Google Scholar : PubMed/NCBI
15	Wang PR, Wang JS, Zhang C, Song XF, Tian N and Kong LY: Huang-Lian-Jie-Du-Decotion induced protective autophagy against the injury of cerebral ischemia/reperfusion via MAPK-mTOR signaling pathway. J Ethnopharmacol. 149:270–280. 2013. View Article : Google Scholar : PubMed/NCBI
16	Zhang F, Wang S, Signore AP and Chen J: Neuroprotective effects of leptin against ischemic injury induced by oxygen-glucose deprivation and transient cerebral ischemia. Stroke. 38:2329–2336. 2007. View Article : Google Scholar : PubMed/NCBI
17	Kilic E, Kilic U, Soliz J, Bassetti CL, Gassmann M and Hermann DM: Brain-derived erythropoietin protects from focal cerebral ischemia by dual activation of ERK-1/-2 and Akt pathways. FASEB J. 19:2026–2028. 2005.PubMed/NCBI
18	Lange-Asschenfeldt C, Raval AP, Dave KR, Mochly-Rosen D, Sick TJ and Pérez-Pinzón MA: Epsilon protein kinase C mediated ischemic tolerance requires activation of the extracellular regulated kinase pathway in the organotypic hippocampal slice. J Cereb Blood Flow Metab. 24:636–645. 2004. View Article : Google Scholar
19	Tournier C, Hess P, Yang DD, Xu J, Turner TK, Nimnual A, Bar-Sagi D, Jones SN, Flavell RA and Davis RJ: Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science. 288:870–874. 2000. View Article : Google Scholar : PubMed/NCBI
20	Lei K, Nimnual A, Zong WX, Kennedy NJ, Flavell RA, Thompson CB, Bar-Sagi D and Davis RJ: The Bax subfamily of Bcl2-related proteins is essential for apoptotic signal transduction by c-Jun NH(2)-terminal kinase. Mol Cell Biol. 22:4929–4942. 2002. View Article : Google Scholar : PubMed/NCBI
21	Okuno S, Saito A, Hayashi T and Chan PH: The c-Jun N-terminal protein kinase signaling pathway mediates Bax activation and subsequent neuronal apoptosis through interaction with Bim after transient focal cerebral ischemia. J Neurosci. 24:7879–7887. 2004. View Article : Google Scholar