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Schisandrin B Protects against Ischemic Brain Damage by Regulating PI3K/AKT Signaling in Rats

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Abstract

Objective

To explore the effect and mechanism of schisandrin B (Sch B) in the treatment of cerebral ischemia in rats.

Methods

The cerebral ischemia models were induced by middle cerebral artery occlusion (MCAO) and reperfusion. Sprague-Dawley rats were divided into 6 groups using a random number table, including sham, MCAO, MCAO+Sch B (50 mg/kg), MCAO+Sch B (100 mg/kg), MCAO+Sch B (100 mg/kg)+LY294002, and MCAO+Sch B (100 mg/kg)+wortmannin groups. The effects of Sch B on pathological indicators, including neurological deficit scores, cerebral infarct volume, and brain edema, were subsequently studied. Tissue apoptosis was identified by terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining. The protein expressions involved in apoptosis, inflammation response and oxidative stress were examined by immunofluorescent staining, biochemical analysis and Western blot analysis, respectively. The effect of Sch B on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling was also explored.

Results

Sch B treatment decreased neurological deficit scores, cerebral water content, and infarct volume in MCAO rats (P<0.05 or P<0.01). Neuronal nuclei and TUNEL staining indicated that Sch B also reduced apoptosis in brain tissues, as well as the Bax/Bcl-2 ratio and caspase-3 expression (P<0.01). Sch B regulated the production of myeloperoxidase, malondialdehyde, nitric oxide and superoxide dismutase, as well as the release of cytokine interleukin (IL)-1 β and IL-18, in MCAO rats (P<0.05 or P<0.01). Sch B promoted the phosphorylation of PI3K and AKT. Blocking the PI3K/AKT signaling pathway with LY294002 or wortmannin reduced the protective effect of Sch B against cerebral ischemia (P<0.05 or P<0.01).

Conclusions

Sch B reduced apoptosis, inflammatory response, and oxidative stress of MCAO rats by modulating the PI3K/AKT pathway. Sch B had a potential for treating cerebral ischemia.

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Author information

Authors and Affiliations

  1. Department of Neurology, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, Fujian Province, 362000, China

    Quan-long Hong

  2. Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China

    Quan-long Hong, Yi-hang Ding, Jing-yi Chen, Song-sheng Shi, Ri-sheng Liang & Xian-kun Tu

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  1. Quan-long Hong
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  2. Yi-hang Ding
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  4. Song-sheng Shi
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Contributions

Hong QL, Ding YH, Chen JY and Tu XK were responsible for the study conception, design, experimental operation, data analysis, and manuscript drafting. Shi SS, Liang RS and Tu XK contributed to the study conception and wrote the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Xian-kun Tu.

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The authors declare that they have no conflicts of interest to disclose.

Additional information

Supported by the Natural Science Foundation of Fujian Province of China (No. 2022J01245), the Quanzhou City Science & Technology Program of China (No. 2020N020s), and the Excellent Young Scholars Cultivation Project of Fujian Medical University Union Hospital (No. 2022XH040)

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Hong, Ql., Ding, Yh., Chen, Jy. et al. Schisandrin B Protects against Ischemic Brain Damage by Regulating PI3K/AKT Signaling in Rats. Chin. J. Integr. Med. 29, 885–894 (2023). https://doi.org/10.1007/s11655-023-3596-1

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  • DOI: https://doi.org/10.1007/s11655-023-3596-1

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