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Ginsenoside Rg2 Ameliorates Brain Injury After Intracerebral Hemorrhage in a Rat Model of Preeclampsia

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Abstract

The incidence of maternal hemorrhagic stroke is elevated in women with preeclampsia during pregnancy. Panax ginseng is a traditional medicinal herb with numerous applications, and ginsenosides are the key bioactive compounds in Panax ginseng. This study aims to evaluate the effects of ginsenoside Rg2 on pregnancy outcomes and brain injury after intracerebral hemorrhage (ICH) in a rat model of preeclampsia. Preeclampsia was induced in rats by N(ω)-nitro-L-arginine methyl ester. Then, an ICH model was prepared by intrastriatal injection of bacterial collagenase. Ginsenoside Rg2 markedly elevated the survival ratio of fetuses. The placental and body weights were increased in the ginsenoside Rg2 group. Compared with the preeclampsia group, the Garcia test score of ginsenoside Rg2–treated rats was significantly increased. Ginsenoside Rg2 treatment ameliorated the ICH-induced augmentation of Evans blue extravasation, inhibited the ICH-induced elevation of brain water content, and reduced the interleukin-1β and tumor necrosis factor-α levels in the hemorrhagic hemisphere after ICH in preeclampsia model rats. Furthermore, ginsenoside Rg2 treatment not only inhibited augmentation of TLR-4, MyD88, p-IκBα, and p-NF-κB expression but also abated the reduction of occludin and claudin-5 expression in the hemorrhagic hemisphere. The findings indicated that ginsenoside Rg2 improved pregnancy outcomes in a rat model of preeclampsia without decreasing the blood pressure and urine protein level. The findings also demonstrated that ginsenoside Rg2 ameliorated ICH-induced neurological disorder and blood–brain barrier dysfunction in an animal model of preeclampsia by regulating the TLR4/NF-κB signaling pathway.

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Data Availability

All data generated or used during the study are available from the corresponding author by request.

Abbreviations

L-NAME:

N(G)-nitro-L-arginine methyl ester

ICH:

Intracerebral hemorrhage

BBB:

Blood–brain barrier

References

  1. Abalos E, Cuesta C, Grosso AL, Chou D, Say L. Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2013;170(1):1–7.

    Article  PubMed  Google Scholar 

  2. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130–7.

    Article  PubMed  Google Scholar 

  3. Moster D, Lie RT, Markestad T. Long-term medical and social consequences of preterm birth. N Engl J Med. 2008;359(3):262–73.

    Article  CAS  PubMed  Google Scholar 

  4. Wu P, Haththotuwa R, Kwok CS, Babu A, Kotronias RA, Rushton C, et al. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2017;10(2):e003497.

    Article  PubMed  Google Scholar 

  5. Swartz RH, Cayley ML, Foley N, Ladhani NNN, Leffert L, Bushnell C, et al. The incidence of pregnancy-related stroke: a systematic review and meta-analysis. Int J Stroke. 2017;12(7):687–97.

    Article  PubMed  Google Scholar 

  6. Sells CM, Feske SK. Stroke in pregnancy. Semin Neurol. 2017;37(6):669–78.

    Article  PubMed  Google Scholar 

  7. Crovetto F, Somigliana E, Peguero A, Figueras F. Stroke during pregnancy and pre-eclampsia. Curr Opin Obstet Gynecol. 2013;25(6):425–32.

    Article  PubMed  Google Scholar 

  8. Marshman L, Aspoas A, Rai M, Chawda S. The implications of ISAT and ISUIA for the management of cerebral aneurysms during pregnancy. Neurosurg Rev. 2007;30(3):177–80.

    Article  PubMed  Google Scholar 

  9. Lee J, Park K, Cho I. Panax ginseng: a candidate herbal medicine for autoimmune disease. J Ginseng Res. 2019;43(3):342–8.

    Article  PubMed  Google Scholar 

  10. Zhao B, Lv C, Lu J. Natural occurring polysaccharides from Panax ginseng C. A. Meyer: A review of isolation, structures, and bioactivities. Int J Biol Macromol. 2019;33:324–36.

    Article  Google Scholar 

  11. Vogler B, Pittler M, Ernst E. The efficacy of ginseng. A systematic review of randomized clinical trials. Eur J Clin Pharmacol. 1999;55(8):567–75.

    Article  CAS  PubMed  Google Scholar 

  12. Ren Y, Wang JL, Zhang X, Wang H, Ye Y, Song L, et al. Antidepressant-like effects of ginsenoside Rg2 in a chronic mild stress model of depression. Brain Res Bull. 2017;134:211–9.

    Article  CAS  PubMed  Google Scholar 

  13. Zhang G, Liu A, Zhou Y, San X, Jin T, Jin Y. Panax ginseng ginsenoside-Rg2 protects memory impairment via anti-apoptosis in a rat model with vascular dementia. J Ethnopharmacol. 2008;115(3):441–8.

    Article  CAS  PubMed  Google Scholar 

  14. Gao Z, Ju R, Luo M, Wu S, Zhang W. The anxiolytic-like effects of ginsenoside Rg2 on an animal model of PTSD. Psychiatry Res. 2019;279:130–7.

    Article  CAS  PubMed  Google Scholar 

  15. Li B, Zhang Y, Li H, Shen H, Wang Y, Li X, et al. Miro1 Regulates neuronal mitochondrial transport and distribution to alleviate neuronal damage in secondary brain injury after intracerebral hemorrhage in rats. Cell Mol Neurobiol. 2020; 41(4):795–812.

  16. Garcia J, Wagner S, Liu K, Hu X. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke. 1995;26(4):627–34.

    Article  CAS  PubMed  Google Scholar 

  17. Zeng Z, Gong X, Hu Z. L-3-n-butylphthalide attenuates inflammation response and brain edema in rat intracerebral hemorrhage model. Aging. 2020;12(12):11768–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wang T, Nowrangi D, Yu L, Lu T, Tang J, Han B, et al. Activation of dopamine D1 receptor decreased NLRP3-mediated inflammation in intracerebral hemorrhage mice. J Neuroinflammation. 2018;15(1):2.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lowry O, Rosebrough N, Farr A, Randall R. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265–75.

    Article  CAS  PubMed  Google Scholar 

  20. Yang S, Song L, Shi X, Zhao N, Ma Y. Ameliorative effects of pre-eclampsia by quercetin supplement to aspirin in a rat model induced by L-NAME. Biomed Pharmacother. 2019;116:108969.

    Article  CAS  PubMed  Google Scholar 

  21. Zuo J, Jiang Z. Melatonin attenuates hypertension and oxidative stress in a rat model of L-NAME-induced gestational hypertension. Vasc Med. 2020;25(4):295–301.

    Article  CAS  PubMed  Google Scholar 

  22. Lu S, Lin Q, Li Y, Jiang X. Synthesis of Nomega-nitro-l-arginine methyl ester modified reduced graphene oxide nanosheets and their protective action on experimental preeclampsia in mice. J Photochem Photobiol B. 2019;194:183–7.

    Article  CAS  PubMed  Google Scholar 

  23. Li Y, Yang N, Wang B, Niu X, Cai W, Li Y, et al. Effect and mechanism of prophylactic use of tadalafil during pregnancy on l-NAME-induced preeclampsia-like rats. Placenta. 2020;99:35–44.

    Article  CAS  PubMed  Google Scholar 

  24. Amaral T, Ognibene D, Carvalho L, Rocha A, Costa C, Moura R, et al. Differential responses of mesenteric arterial bed to vasoactive substances in L-NAME-induced preeclampsia: Role of oxidative stress and endothelial dysfunction. Clin Exp Hypertens. 2018;40(2):126–35.

    Article  CAS  PubMed  Google Scholar 

  25. Zambrano M, Miller E. Maternal stroke: an update. Curr Atheroscler Rep. 2019;21(9):33.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Betz A, Iannotti F, Hoff J. Brain edema: a classification based on blood-brain barrier integrity. Cerebrovasc Brain Metab Rev. 1989;1(2):133–54.

    CAS  PubMed  Google Scholar 

  27. Huber J, Egleton R, Davis T. Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. Trends Neurosci. 2001;24(12):719–25.

    Article  CAS  PubMed  Google Scholar 

  28. Zhang Y, Deng H, Hu Y, Pan C, Wu G, Li Q, et al. Adipose-derived mesenchymal stem cells stereotactic transplantation alleviate brain edema from intracerebral hemorrhage. J Cell Biochem. 2019;120(9):14372–82.

    Article  CAS  PubMed  Google Scholar 

  29. Xi G, Keep R, Hoff J. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5(1):53–63.

    Article  PubMed  Google Scholar 

  30. Tschoe C, Bushnell CD, Duncan PW, Alexander-Miller MA, Wolfe SQ. Neuroinflammation after intracerebral hemorrhage and potential therapeutic targets. J Stroke. 2020;22(1):29–46.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Sansing LH, Harris TH, Welsh FA, Kasner SE, Hunter CA, Kariko K. Toll-like receptor 4 contributes to poor outcome after intracerebral hemorrhage. Ann Neurol. 2011;70(4):646–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhao X, Zhang Y, Strong R, Zhang J, Grotta J, Aronowski J. Distinct patterns of intracerebral hemorrhage-induced alterations in NF-κB subunit, iNOS, and COX-2 expression. J Neurochem. 2007;101(3):652–63.

    Article  CAS  PubMed  Google Scholar 

  33. Wang J, Dore S. Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab. 2007;27(5):894–908.

    Article  CAS  PubMed  Google Scholar 

  34. Lin S, Yin Q, Zhong Q, Lv FL, Zhou Y, Li JQ, et al. Heme activates TLR4-mediated inflammatory injury via MyD88/TRIFsignaling pathway in intracerebral hemorrhage. J Neuroinflammation. 2012;9:46.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Abbott N. Inflammatory mediators and modulation of blood–brain barrier permeability. Cell Mol Neurobiol. 2000;20(2):131–47.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Lisa Kreiner, PhD, from Liwen Bianji, (Edanz) (www.liwenbianji.cn/), and Prof. Lon Clark for editing the English text of a draft of this manuscript.

Funding

The work was supported by the National Natural Science Foundation of China (grant number 81473378); the Natural Science Foundation of Jilin Province (grant number 20170101002JC); and the Jilin Scientific and Technological Development Program (grant number 20190103084JH).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, People’s Republic of China

    Liying Cai, Feifei Hu, Weijie Zhong & Fangcong Liu

  2. Department of Pharmacology, School of Pharmacy, Jilin University, Changchun, 130021, People’s Republic of China

    Wenwen Fu, Xiaofeng Yu & Dayuan Sui

  3. School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, People’s Republic of China

    Tian Wang

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  1. Liying Cai
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  2. Feifei Hu
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  3. Wenwen Fu
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  4. Xiaofeng Yu
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  7. Tian Wang
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Contributions

TW and DS: conceptualization, supervision, review, and editing. LC, FH, WF, XY: methodology, formal analysis, investigation, data curation. LC, WZ, FL: writing of original draft.

Corresponding authors

Correspondence to Tian Wang or Dayuan Sui.

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Ethics Approval

The experiments were approved by the Ethics Committee of Jilin University (JU19812) and were conducted according to the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals (publication 86-23, revised in 1986).

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Not applicable.

Conflict of Interest

The authors declare no competing interests.

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The funding agencies had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.

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Cai, L., Hu, F., Fu, W. et al. Ginsenoside Rg2 Ameliorates Brain Injury After Intracerebral Hemorrhage in a Rat Model of Preeclampsia. Reprod. Sci. 28, 3431–3439 (2021). https://doi.org/10.1007/s43032-021-00692-2

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  • DOI: https://doi.org/10.1007/s43032-021-00692-2

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