Skip to main content

Advertisement

SpringerLink
Log in

The Effect and Mechanism of Syringa pinnatifolia Hemsl. Ligans on Cerebral Ischemia-Reperfusion Injury and Oxidative Stress in Mice

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Lignans are the main components of Syringa pinnatifolia Hemsl. (SP). Previous studies have shown that SP lignans (SPL) can considerably improve CCl4-induced acute liver injury in mice by the anti-oxidative stress (OS) mechanism. In this study, we investigated the antioxidant effects of SPL on cerebral ischemia/reperfusion injury (CIRI) and its underlying molecular mechanism. We developed a middle cerebral artery occlusion/reperfusion (MCAO/R) model in mice to achieve CIRI and orally administered SPL daily for 1–3 days. We evaluated neurological function deficits and performed hematoxylin and eosin staining. We further calculated the infarct volume. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the brain were detected using corresponding kits. The transcription and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and NAD(P)H quinone dehydrogenase 1 (NQO1) in brain tissues were analyzed by real-time reverse transcription polymerase chain reaction and western blotting, respectively. The results showed that SPL could remarkably ameliorate neurological functions and pathological damage in brain tissues, reducing the cerebral infarct volume. It also increased the SOD and GPx activities decreased the MDA levels as well as inhibited the expression of (NOX)2 and NOX4. We also found that the mRNA and protein levels of Nrf2, HO-1, and NQO1 in the CIRI mice increased transiently and peaked at 24 h of reperfusion, and then began to decline. SPL could reverse decreasing Nrf2 and HO-1 levels after 24 h. In conclusion, SPL can alleviate CIRI and OS by activating the Nrf2/HO-1 pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available due to [REASON(S) WHY DATA ARE NOT PUBLIC] but are available from the corresponding author on reasonable request.

References

  1. Liu L, Chen M, Lin K, Xiang X, Yang J, Zheng Y, Xiong X, Zhu S (2020) TRPC6 attenuates cortical astrocytic apoptosis and inflammation in cerebral ischemic/reperfusion injury. Front Cell Dev Biol 8:594283. https://doi.org/10.3389/fcell.2020.594283

    Article  PubMed  Google Scholar 

  2. Shao Z, Dou S, Zhu J, Wang H, Xu D, Wang C, Cheng B, Bai B (2020) The role of mitophagy in ischemic stroke. Front Neurol 11:608610. https://doi.org/10.3389/fneur.2020.608610

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bao LE, Er D (2015) Evaluation of the therapeutic effect of dynamic treatment of ischemic stroke based on syndrome differentiation of mongolian medicine. Chin J Ethnomed Ethnopharmacy 24:1–2 (in Chinese)

    Google Scholar 

  4. Meng F, Ke J, Li J, Zhao C, Yan J, Wang L (2022) A deuterohemin peptide protects cerebral ischemia-reperfusion injury by preventing oxidative stress in vitro and in vivo. Exp Cell Res 422:113432. https://doi.org/10.1016/j.yexcr.2022.113432

    Article  CAS  PubMed  Google Scholar 

  5. Su GZ, Chen J, Cao Y, Bai RF, Chen SYL, Tu PF, Chai XY (2015) Phytochemical and pharmacological progress on peeled stem of Syringa pinnatifolia, a mongolian folk medicine. China J Chin Materia Med 40:4333–4338 (in Chinese)

    CAS  Google Scholar 

  6. Penumathsa SV, Koneru S, Zhan L, John S, Menon VP, Prasad K, Maulik N (2008) Secoisolariciresinol diglucoside induces neovascularization-mediated cardioprotection against ischemia-reperfusion injury in hypercholesterolemic myo cardium. J Mol Cell Cardio 44:170–179. https://doi.org/10.1016/j.yjmcc.2007.09.014

    Article  CAS  Google Scholar 

  7. Xie LR, Liu X (2015) Study on protein expression of brain-heart prescription anti-myocardial ischemia based on the theory of “brain-heart treatment”. Dissertation, Beijing University of Chinese Medicine. (in Chinese)

  8. Guo H, Adah D, James PB, Liu Q, Li G, Ahmadu P, Chai L, Wang S, Liu Y, Hu L (2018) Xueshuantong injection (lyophilized) attenuates cerebral ischemia/reperfusion injury by the activation of Nrf2-VEGF pathway. Neurochem Res 43:1096–1103. https://doi.org/10.1007/s11064-018-2523-x

    Article  CAS  PubMed  Google Scholar 

  9. Zhang W, Wei R, Zhang L, Tan Y, Qian C (2017) Sirtuin 6 protects the brain from cerebral ischemia/reperfusion injury through NRF2 activation. Neuroscience 366:95–104. https://doi.org/10.1016/j.neuroscience.2017.09.035

    Article  CAS  PubMed  Google Scholar 

  10. Chen X, Xiao Z, Pan Q, Wang L, Hou Q, Lei YC, Wu SZ (2015) Establishment of cerebral ischemia-reperfusion injury model in rats by modified thread embolism method. Med Innov China 12:24–27 (in Chinese)

    Google Scholar 

  11. Liu W (2020) Protective effect and mechanism of Xuesaitong on cerebral ischemia-reperfusion in rats through Nrf2 pathway. Dissertation, Jilin University. (in Chinese)

  12. Gad SN, Nofal S, Raafat EM, Ahmed AAE (2020) Lixisenatide reduced damage in hippocampus CA1 neurons in a rat model of cerebral ischemia-reperfusion possibly via the ERK/P38 signaling pathway. J Mol Neurosci 70:1026–1037. https://doi.org/10.1007/s12031-020-01497-9

    Article  CAS  PubMed  Google Scholar 

  13. Yang J, Wang Z, Liu X, Lu P (2021) Modulation of vascular integrity and neuroinflammation by peroxiredoxin 4 following cerebral ischemia-reperfusion injury. Microvasc Res 135:104144. https://doi.org/10.1016/j.mvr.2021.104144

    Article  CAS  PubMed  Google Scholar 

  14. Orellana-Urzúa S, Rojas I, Líbano L, Rodrigo R (2020) Pathophysiology of ischemic stroke: role of oxidative stress. Curr Pharm Des 26:4246–4260. https://doi.org/10.2174/1381612826666200708133912

    Article  CAS  PubMed  Google Scholar 

  15. Shen J (2012) Reactive nitrogen radicals: a double-edged sword that causes blood-brain barrier destruction and regulates nerve repair during cerebral ischemia-reperfusion injury. Acta Biophys Sinica 28:295–306 (in Chinese)

    Article  CAS  Google Scholar 

  16. Yin M, Liu Z, Wang J, Gao W (2022) Buyang Huanwu decoction alleviates oxidative injury of cerebral ischemia-reperfusion through PKCε/Nrf2 signaling pathway. J Ethnopharmacol 303:115953. https://doi.org/10.1016/j.jep.2022.115953

    Article  CAS  PubMed  Google Scholar 

  17. Deng M, Sun J, Peng L, Huang Y, Jiang W, Wu S, Zhou L, Chung SK, Cheng X (2022) Scutellarin acts on the AR-NOX axis to remediate oxidative stress injury in a mouse model of cerebral ischemia/reperfusion injury. Phytomedicine 103:154214. https://doi.org/10.1016/j.phymed.2022.154214

    Article  CAS  PubMed  Google Scholar 

  18. Yuan Q, Yuan Y, Zheng Y, Sheng R, Liu L, Xie F, Tan J (2021) Anti-cerebral ischemia reperfusion injury of polysaccharides: a review of the mechanisms. Biomed Pharmacother 137:111303. https://doi.org/10.1016/j.biopha.2021.111303

    Article  CAS  PubMed  Google Scholar 

  19. Fu K, Chen M, Zheng H, Li C, Yang F, Niu Q (2021) Pelargonidin ameliorates MCAO-induced cerebral ischemia/reperfusion injury in rats by the action on the Nrf2/HO-1 pathway. Transl Neurosci 12:20–31. https://doi.org/10.1515/tnsci-2021-0006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rodrigo R, Fernández-Gajardo R, Gutiérrez R, Manuel Matamala J, Carrasco R, Miranda-Merchak A, Feuerhake W (2013) Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities. CNS Neurol Disord Drug Targets 12:698–714

    Article  CAS  PubMed  Google Scholar 

  21. He J, Zhou D, Yan B (2020) Eriocitrin alleviates oxidative stress and inflammatory response in cerebral ischemia reperfusion rats by regulating phosphorylation levels of Nrf2/NQO-1/HO-1/NF-κB p65 proteins. Ann Transl Med 8:757. https://doi.org/10.21037/atm-20-4258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cherait A, Maucotel J, Lefranc B, Leprince J, Vaudry D (2020) Intranasal administration of PACAP is an efficient delivery route to reduce infarct volume and promote functional recovery after transient and permanent middle cerebral artery occlusion. Front Endocrinol (Lausanne) 11:585082. https://doi.org/10.3389/fendo.2020.585082

    Article  PubMed  Google Scholar 

  23. Serrano F, Kolluri NS, Wientjes FB, Patrick Card J, Klann E (2003) NADPH oxidase immunoreactivity in the mouse brain. Brain Res 988:193–198. https://doi.org/10.1016/S0006-8993(03)03364-X

    Article  CAS  PubMed  Google Scholar 

  24. Zhou F, Wang M, Ju J, Wang Y, Liu Z, Zhao X, Yan Y, Yan S, Luo X, Fang Y (2019) Schizandrin A protects against cerebral ischemia-reperfusion injury by suppressing inflammation and oxidative stress and regulating the AMPK/Nrf2 pathway regulation. Am J Transl Res 11:199–209

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhu F, Xiong J, Yi F, Luo E, Huang C, Li R (2022) Albiflorin relieves cerebral ischemia-reperfusion injury by activating Nrf2/HO-1 pathway. Histol Histopathol 19:18518. https://doi.org/10.14670/HH-18-518

    Article  Google Scholar 

  26. Shih AY, Li P, Murphy TH (2005) A small-moleculeinducible Nrf2-mediated antioxidant response provides effective prophylaxis against cerebral ischemia in vivo. J Neurosci 25:10321–10335. https://doi.org/10.1523/JNEUROSCI.4014-05.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

  1. School of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China

    Yiwei Hao, Yan Yang, Fuhou Chang, Feng Gao, Xue Zhao, Dongrui Wang, Yuanyuan Qin & Lei Fan

  2. Pharmacy Department, Inner Mongolia Cancer Hospital, Hohhot, Inner Mongolia, China

    Yiwei Hao

  3. School of Basic Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China

    Minjie Wang

Authors
  1. Yiwei Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fuhou Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Minjie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Feng Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xue Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dongrui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yuanyuan Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lei Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YH and YY wrote the main manuscript text and DW, YQ prepared Figs. 1, 2, 3, 4, 5, 6 and 7. MW,  FG and XZ prepared figures. FC analyzed the data. LF proofread the whole manuscript. All authors reviewed the manuscript.

Corresponding author

Correspondence to Lei Fan.

Ethics declarations

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hao, Y., Yang, Y., Chang, F. et al. The Effect and Mechanism of Syringa pinnatifolia Hemsl. Ligans on Cerebral Ischemia-Reperfusion Injury and Oxidative Stress in Mice. Neurochem Res 48, 1822–1834 (2023). https://doi.org/10.1007/s11064-022-03855-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-022-03855-y

Keywords

Search

Navigation