Astragalus Polysaccharide Promotes Neuronal Injury Repair via the Notch1/NFκB Signaling Axis in the Ventroposterior Thalamic Nucleus in Rats with Focal Cerebral Ischemia

Wenjuan Li^1,†, Huachun Miao^1,†, Zeyin Nie¹, Feng Wu¹, Huaibin Li^1,*

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¹ School of basic medical sciences, Wannan Medical College, 241002 Wuhu, Anhui, China

^*Correspondence: 19920001@wnmc.edu.cn (Huaibin Li)
^†These authors contributed equally.

J. Integr. Neurosci. 2024, 23(2), 34; https://doi.org/10.31083/j.jin2302034

Submitted: 24 May 2023 | Revised: 2 September 2023 | Accepted: 12 September 2023 | Published: 18 February 2024

This is an open access article under the CC BY 4.0 license.

Abstract

Background: Ischemic stroke is the most common form of stroke and the second most common cause of death and incapacity worldwide. Its pathogenesis and treatment have been the focus of considerable research. In traditional Chinese medicine, the root of Mongolian astragalus has been important in the treatment of stroke since ancient times. Astragalus polysaccharide (APS) is a key active ingredient of astragalus and offers therapeutic potential for conditions affecting the neurological system, the heart, cancer, and other disorders. However, it is not yet known how APS works to protect against ischemic stroke. Methods: Rats were subjected to middle cerebral artery occlusion (MCAO) to imitate localized cerebral ischemia. Each of four experimental groups (normal, sham, MCAO, and MCAO+APS) contained 12 adult male Sprague-Dawley (SD) rats selected randomly from a total of 48 rats. Following successful establishment of the model, rats in the MCAO+APS group received intraperitoneal injection of APS (50 mg/kg) once daily for 14 days, whereas all other groups received no APS. The Bederson nerve function score and the forelimb placement test were used to detect motor and sensory function defects, while Nissl staining was used to investigate pathological defects in the ventroposterior thalamic nucleus (VPN). Immunohistochemical staining and Western blot were used to evaluate the expression of Neurogenic locus notch homolog protein 1 (Notch1), hairy and enhancer of split 1 (Hes1), phospho-nuclear factor- $\kappa{}$ B p65 (p-NF $\kappa{}$ B p65), and nuclear factor- $\kappa{}$ B p65 (NF $\kappa{}$ B p65) proteins in the VPN on the ischemic side of MCAO rats. Results: APS promoted the recovery of sensory and motor function, enhanced neuronal morphology, increased the number of neurons, and inhibited the expression of Notch1/NF $\kappa{}$ B signaling pathway proteins in the VPN of rats with cerebral ischemia. Conclusion: After cerebral ischemia, APS can alleviate symptoms of secondary damage to the VPN, which may be attributed to the suppression of the Notch1/NF $\kappa{}$ B pathway.

Keywords

cerebral ischemia

astragalus polysaccharide

VPN

Notch1

Hes1

p-NFκB p65

Funding

WK2022XS45/Research Fund Project of Wannan Medical College

KJ2020A0603/Collegiate Major Natural Science Research Projects of Anhui Province

2019jxtd072/Teaching and Research Project of Anhui Provincial Department of Education

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Fig. 1.

Experimental design and behavioral tests. (A) Schematic of the study design. (B) Schematic diagram of statistical area for counting positive cells by Nissl and immunohistochemical staining. (C) Bederson nerve function score; n = 12 per group; ***p $<$ 0.001, compared with the sham group; ${}^{\#}$ p $<$ 0.05, compared with the MCAO group. (D) Forelimb placement test; n = 12 per group; ***p $<$ 0.001, compared with the sham group; ${}^{\#}$ p $<$ 0.05, compared with the MCAO group. MACO, middle cerebral artery occlusion; APS, Astragalus polysaccharide.

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J. Integr. Neurosci. Print ISSN 0219-6352 Electronic ISSN 1757-448X