Skip to main content

Advertisement

SpringerLink
Log in

Geniposide attenuates early brain injury by inhibiting oxidative stress and neurocyte apoptosis after subarachnoid hemorrhage in rats

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Oxidative stress and neurocyte apoptosis are crucial pathophysiological process in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Geniposide (GNP) has been reported to exert neuroprotective effects by reducing oxidative injury and neurocyte apoptosis. However, the effect of GNP has not been clarified in EBI after SAH. The study was performed to evaluate the neuroprotective effects and mechanisms of GNP in EBI after SAH.

Methods and results

A total of 60 male Wistar rats were randomly divided into five groups. The prechiasmatic cistern SAH model was used in this study. SAH grade was evaluated using a grading system. Neurological function was evaluated using the Garcia scores. Brain edema was measured by the wet-dry method. Blood–brain barrier (BBB) permeability was measured by the extravasation of Evans Blue (EB). The neurocyte apoptosis was observed using TUNEL assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), glutathione S-transferase (GST) and quinone oxidoreductase-1 (NQO-1) were performed. The results showed that GNP reduced brain edema, attenuated BBB permeability, inhibited neurocyte apoptosis and improved neurological function. Moreover, GNP also decreased the levels of ROS and MDA, elevated Nrf2 expression in the temporal cortex and up-regulated the expression of NQO-1, HO-1 and GST after SAH.

Conclusions

GNP could ameliorate oxidative stress and neurocyte apoptosis to exert neuroprotective effects by Nrf2 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

Similar content being viewed by others

References

  1. Lawton MT, Vates GE (2017) Subarachnoid hemorrhage. N Engl J Med 377:257–266. https://doi.org/10.1056/NEJMcp1605827

    Article  PubMed  Google Scholar 

  2. Chen S, Xu P, Fang Y, Lenahan C (2020) The updated role of the blood brain barrier in subarachnoid hemorrhage: from basic and clinical studies. Curr Neuropharmacol 18:1266–1278. https://doi.org/10.2174/1570159x18666200914161231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Yang Y, Chen S, Zhang JM (2017) The updated role of oxidative stress in subarachnoid hemorrhage. Curr Drug Deliv 14:832–842. https://doi.org/10.2174/1567201813666161025115531

    Article  CAS  PubMed  Google Scholar 

  4. Hasegawa Y, Suzuki H, Sozen T, Altay O, Zhang JH (2011) Apoptotic mechanisms for neuronal cells in early brain injury after subarachnoid hemorrhage. Acta Neurochir Suppl 110:43–48. https://doi.org/10.1007/978-3-7091-0353-1_8

    Article  PubMed  Google Scholar 

  5. Chen S, Feng H, Sherchan P, Klebe D, Zhao G, Sun X, Zhang J, Tang J, Zhang JH (2014) Controversies and evolving new mechanisms in subarachnoid hemorrhage. Prog Neurobiol 115:64–91. https://doi.org/10.1016/j.pneurobio.2013.09.002

    Article  PubMed  Google Scholar 

  6. Bellezza I, Giambanco I, Minelli A, Donato R (2018) Nrf2-Keap1 signaling in oxidative and reductive stress. Biochim Biophys Acta Mol Cell Res 1865:721–733. https://doi.org/10.1016/j.bbamcr.2018.02.010

    Article  CAS  PubMed  Google Scholar 

  7. Ahmed SM, Luo L, Namani A, Wang XJ, Tang X (2017) Nrf2 signaling pathway: pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis 1863:585–597. https://doi.org/10.1016/j.bbadis.2016.11.005

    Article  CAS  PubMed  Google Scholar 

  8. Zhou YX, Zhang RQ, Rahman K, Cao ZX, Zhang H, Peng C (2019) Diverse pharmacological activities and potential medicinal benefits of geniposide. Evid Based Complement Alternat Med 2019:4925682. https://doi.org/10.1155/2019/4925682

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ma J, Ding Y (2018) Geniposide suppresses growth, migration and invasion of MKN45 cells by down-regulation of lncRNA HULC. Exp Mol Pathol 105:252–259. https://doi.org/10.1016/j.yexmp.2018.08.011

    Article  CAS  PubMed  Google Scholar 

  10. Lv C, Liu X, Liu H, Chen T, Zhang W (2014) Geniposide attenuates mitochondrial dysfunction and memory deficits in APP/PS1 transgenic mice. Curr Alzheimer Res 11:580–587. https://doi.org/10.2174/1567205011666140618095925

    Article  CAS  PubMed  Google Scholar 

  11. Lu W, Zhao Y, Kong Y, Zhang W, Ma W, Li W, Wang K (2018) Geniposide prevents H(2) O(2) -induced oxidative damage in melanocytes by activating the PI3K-Akt signalling pathway. Clin Exp Dermatol 43:667–674. https://doi.org/10.1111/ced.13409

    Article  CAS  PubMed  Google Scholar 

  12. Cheng S, Zhou F, Xu Y, Liu X, Zhang Y, Gu M, Su Z, Zhao D, Zhang L, Jia Y (2019) Geniposide regulates the miR-101/MKP-1/p38 pathway and alleviates atherosclerosis inflammatory injury in ApoE(-/-) mice. Immunobiology 224:296–306. https://doi.org/10.1016/j.imbio.2018.12.005

    Article  CAS  PubMed  Google Scholar 

  13. Liu F, Wang Y, Yao W, Xue Y, Zhou J, Liu Z (2019) Geniposide attenuates neonatal mouse brain injury after hypoxic-ischemia involving the activation of PI3K/Akt signaling pathway. J Chem Neuroanat 102:101687. https://doi.org/10.1016/j.jchemneu.2019.101687

    Article  CAS  PubMed  Google Scholar 

  14. Cheng F, Ma C, Sun L, Zhang X, Zhai C, Li C, Zhang S, Ren B, Liu S, Liu S, Yin X, Wang X, Wang Q (2018) Synergistic neuroprotective effects of Geniposide and ursodeoxycholic acid in hypoxia-reoxygenation injury in SH-SY5Y cells. Exp Ther Med 15:320–326. https://doi.org/10.3892/etm.2017.5395

    Article  CAS  PubMed  Google Scholar 

  15. Li S, Xiao X, Ni X, Ye Z, Zhao J, Hang C (2017) Tetramethylpyrazine Protects against Early Brain Injury after Experimental Subarachnoid Hemorrhage by Affecting Mitochondrial-Dependent Caspase-3 Apoptotic Pathway. Evid Based Complement Alternat Med 2017:3514914. https://doi.org/10.1155/2017/3514914

    Article  PubMed  PubMed Central  Google Scholar 

  16. Chen JH, Wu T, Xia WY, Shi ZH, Zhang CL, Chen L, Chen QX, Wang YH (2020) An early neuroprotective effect of atorvastatin against subarachnoid hemorrhage. Neural Regen Res 15:1947–1954. https://doi.org/10.4103/1673-5374.280326

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sugawara T, Ayer R, Jadhav V, Zhang JH (2008) A new grading system evaluating bleeding scale in filament perforation subarachnoid hemorrhage rat model. J Neurosci Methods 167:327–334. https://doi.org/10.1016/j.jneumeth.2007.08.004

    Article  PubMed  Google Scholar 

  18. Mo J, Enkhjargal B, Travis ZD, Zhou K, Wu P, Zhang G, Zhu Q, Zhang T, Peng J, Xu W, Ocak U, Chen Y, Tang J, Zhang J, Zhang JH (2019) AVE 0991 attenuates oxidative stress and neuronal apoptosis via Mas/PKA/CREB/UCP-2 pathway after subarachnoid hemorrhage in rats. Redox Biol 20:75–86. https://doi.org/10.1016/j.redox.2018.09.022

    Article  CAS  PubMed  Google Scholar 

  19. Zhuang K, Zuo YC, Sherchan P, Wang JK, Yan XX, Liu F (2019) Hydrogen inhalation attenuates oxidative stress related endothelial cells injury after subarachnoid hemorrhage in rats. Front Neurosci 13:1441. https://doi.org/10.3389/fnins.2019.01441

    Article  PubMed  Google Scholar 

  20. Zhang T, Wu P, Budbazar E, Zhu Q, Sun C, Mo J, Peng J, Gospodarev V, Tang J, Shi H, Zhang JH (2019) Mitophagy reduces oxidative stress via Keap1 (Kelch-Like epichlorohydrin-associated protein 1)/Nrf2 (nuclear factor-E2-related factor 2)/PHB2 (prohibitin 2) pathway after subarachnoid hemorrhage in rats. Stroke 50:978–988. https://doi.org/10.1161/strokeaha.118.021590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Pang J, Chen Y, Kuai L, Yang P, Peng J, Wu Y, Chen Y, Vitek MP, Chen L, Sun X, Jiang Y (2017) Inhibition of blood-brain barrier disruption by an apolipoprotein E-mimetic peptide ameliorates early brain injury in experimental subarachnoid hemorrhage. Transl Stroke Res 8:257–272. https://doi.org/10.1007/s12975-016-0507-1

    Article  CAS  PubMed  Google Scholar 

  22. Zhang X, Wu Q, Lu Y, Wan J, Dai H, Zhou X, Lv S, Chen X, Zhang X, Hang C, Wang J (2018) Cerebroprotection by salvianolic acid B after experimental subarachnoid hemorrhage occurs via Nrf2- and SIRT1-dependent pathways. Free Radic Biol Med 124:504–516. https://doi.org/10.1016/j.freeradbiomed.2018.06.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wu Q, Zhang XS, Wang HD, Zhang X, Yu Q, Li W, Zhou ML, Wang XL (2014) Astaxanthin activates nuclear factor erythroid-related factor 2 and the antioxidant responsive element (Nrf2-ARE) pathway in the brain after subarachnoid hemorrhage in rats and attenuates early brain injury. Mar Drugs 12:6125–6141. https://doi.org/10.3390/md12126125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by Project of Administration of Traditional Chinese Medicine of Guangdong Province of China (No.20211157).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China

    Xiaolan Xiao

  2. The Second Institute of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China

    Shuangxi Sun

  3. Department of Neurosurgery, Hospital of Guangzhou University Mega Center, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, Guangdong Province, China

    Yingbin Li & Jun Cai

  4. Department of Neurosurgery, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China

    Xuecheng Cen & Shaoxue Li

  5. Neurological Intensive Care Unit, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China

    Shibiao Wu & Aili Lu

  6. Department of Neurosurgery, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK

    Junjie Zhao

Authors
  1. Xiaolan Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuangxi Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yingbin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xuecheng Cen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shibiao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aili Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jun Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Junjie Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shaoxue Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S-X L designed the experiments. S-X S, Y-B L, X-C C, S-B W and J-J Z performed the material preparation and experiments. X-L X and A-L L analyzed the data and wrote the manuscript. S-X L and JC revised the manuscript. All authors approved the publication the manuscript.

Corresponding author

Correspondence to Shaoxue Li.

Ethics declarations

Conflict of interest

All authors declare no potential conflicts of interest.

Ethical approval

Animal studies were conducted in accordance with the requirements of the directory of the Ethical Treatment of Experimental Animals of China. This study was approved by the Ethics Committee of the Guangdong Provincial Hospital of Chinese Medicine.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiao, X., Sun, S., Li, Y. et al. Geniposide attenuates early brain injury by inhibiting oxidative stress and neurocyte apoptosis after subarachnoid hemorrhage in rats. Mol Biol Rep 49, 6303–6311 (2022). https://doi.org/10.1007/s11033-022-07438-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-022-07438-6

Keywords

Search

Navigation