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Salidroside attenuates cerebral ischemia/reperfusion injury by regulating TSC2-induced autophagy

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Abstract

Salidroside (SAL), an antioxidant derived from Rhodiola rosea, exerts neuroprotective effects in cerebral ischemia/reperfusion (I/R) injury; however, the mechanisms have not been fully elucidated. The present study established a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a cellular model of oxygen–glucose deprivation/reoxygenation (OGD/R) to explore the roles and mechanisms of SAL in cerebral I/R injury. The rat model of MCAO/R was established and rats were treated with different doses of SAL. The Zea-Longa scoring system and 2,3,5-triphenyltetrazolium chloride (TTC) staining showed that SAL reduced neurological deficit scores and cerebral infarct volumes in MCAO/R rats. The results of Morris water maze (MWM) test showed that SAL reduced memory impairment in MCAO/R rats. In addition, SAL significantly reduced oxidative stress and suppressed inflammatory response. Next, the OGD/R model was established with PC12 cells and treated with SAL. The results of flow cytometry and 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assays showed that SAL reduced apoptosis, enhanced cell viability and protected neuronal cells from damage by decreasing lactate dehydrogenase (LDH) activity. SAL increased the expression of TSC complex subunit 2 (TSC2), and activated the 5′-AMP-activated protein kinase (AMPK) and inhibited the mammalian target of rapamycin (mTOR) signaling pathways. It was verified that SAL alleviated cerebral I/R injury by regulating the AMPK/TSC2/mTOR pathway to induce autophagy. In conclusion, SAL reduces the inflammatory response and oxidative stress in a concentration-dependent manner, and protects against cerebral I/R injury by modulating TSC2-induced autophagy. These findings suggest SAL may prove to be a potential therapeutic agent for ischemic stroke.

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Availability of supporting data

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

The present study was supported by Xinjiang Uygur Autonomous Region Health young medical science and technology talents special research project (No. wjwy-202026) and General projects of Natural Science Foundation of Xinjiang Uygur Autonomous Region (No. 2021D01C131).

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Authors and Affiliations

  1. Department of Rehabilitation Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91, Tianchi Road, Tianshan District, Ürümqi, 830001, Xinjiang, China

    Chunli Li, Jiejun Chi, Ming Liang, Yangyang Wang, Songxin Tian, Huiyan Zhu & Hai Xu

  2. Function Center School of Basic Medical Sciences, Xinjiang Medical University, Ürümqi, 830054, Xinjiang, China

    Hongyan Dai

Authors
  1. Chunli Li
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  2. Jiejun Chi
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  3. Hongyan Dai
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  4. Ming Liang
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  5. Yangyang Wang
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  6. Songxin Tian
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  7. Huiyan Zhu
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  8. Hai Xu
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Contributions

CL conducted the conception and design, HD performed the animal study; JC analyzed the data; YW, ST drafted the manuscript; HZ did the literature research; HX conducted the conception and design, revised the manuscript. CL and HX confirm the authenticity of all the raw data.

Corresponding author

Correspondence to Hai Xu.

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Conflict of interest

The authors have no conflicts of interest to declare.

Ethical approval and consent to participate

All animal experiments were approved by the Animal Ethics Council of People’s Hospital of Xinjiang Uygur Autonomous Region (No. 2020–03241).

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Additional information

Communicated by Sreedharan Sajikumar.

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Li, C., Chi, J., Dai, H. et al. Salidroside attenuates cerebral ischemia/reperfusion injury by regulating TSC2-induced autophagy. Exp Brain Res 241, 113–125 (2023). https://doi.org/10.1007/s00221-022-06493-6

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  • DOI: https://doi.org/10.1007/s00221-022-06493-6

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