Skip to main content

Advertisement

SpringerLink
Log in

Albiflorin attenuates high glucose-induced endothelial apoptosis via suppressing PARP1/NF-κB signaling pathway

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

Abstract

Objective

Paeonia lactiflora Pall has long been recognized as an anti-inflammatory traditional Chinese herbal medicine. We aimed to study the pharmacological action of albiflorin, an active ingredient extracted from the roots of Paeonia lactiflora Pall, on diabetic vascular complications.

Methods

Human umbilical vein endothelial cells (HUVECs) were stimulated with high glucose and treated with 5, 10, and 20 μM albiflorin. CCK-8 assay, EdU staining, Annexin V-FITC staining, transwell assay, scratch test, RT-PCR, ELISA, Western blot, and immunofluorescence were carried out. SwissTargetPrediction database was used for screening targets of albiflorin and molecular docking was done using Autodock Vina software.

Results

Albiflorin treatment dose-dependently alleviated high glucose-induced viability loss of HUVECs. In addition, albiflorin promoted the proliferation and migration, while inhibited apoptosis and the release of TNF-α, IL-6, and IL-1β in HUVECs. PARP1 was predicted and confirmed to be a target for albiflorin in vitro. Albiflorin targeted PARP1 to inhibit the activation of NF-κB. Transfection of HUVECs with PARP1 overexpression plasmids effectively reversed the effects of albiflorin on high glucose-treated HUVECs.

Conclusions

Albiflorin suppressed high glucose-induced endothelial cell apoptosis and inflammation, suggesting its potential in treating diabetic vascular complications. The action of albiflorin possibly caused by its regulation on inhibiting PARP1/NF-κB signaling.

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

Similar content being viewed by others

Data availability

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

Abbreviations

IDF:

International Diabetes Federation

NF:

Nuclear factor

ox-LDL:

Oxidized low-density lipoprotein

PARP1:

Poly(ADP-ribose) polymerase-1

T2DM:

Type 2 diabetes mellitus

References

  1. Barnett R. Type 2 diabetes. Lancet. 2019;394(10198):31728–31723.

    Article  Google Scholar 

  2. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88–98.

    Article  Google Scholar 

  3. Wang HH, Garruti G, Liu M, Portincasa P, Wang DQ. Cholesterol and lipoprotein metabolism and atherosclerosis: recent advances in reverse cholesterol transport. Ann Hepatol. 2017;16:s27–42.

    Article  CAS  Google Scholar 

  4. Calkin AC, Allen TJ. Diabetes mellitus-associated atherosclerosis: mechanisms involved and potential for pharmacological invention. Am J Cardiovasc Drugs. 2006;6(1):15–40.

    Article  CAS  Google Scholar 

  5. Ridker PM, Lüscher TF. Anti-inflammatory therapies for cardiovascular disease. Eur Heart J. 2014;35(27):1782–91.

    Article  CAS  Google Scholar 

  6. Liu J, Jiang C, Ma X, Wang J. Notoginsenoside Fc attenuates high glucose-induced vascular endothelial cell injury via upregulation of PPAR-γ in diabetic Sprague-Dawley rats. Vascul Pharmacol. 2018;109:27–35.

    Article  CAS  Google Scholar 

  7. Zhu Q, Kang J, Xu G, Li J, Zhou H, Liu Y. Traditional Chinese medicine Shenqi compound to improve lower extremity atherosclerosis of patients with type 2 diabetes by affecting blood glucose fluctuation: Study protocol for a randomized controlled multicenter trial. Medicine. 2020;99(11):0000000000019501.

    Article  Google Scholar 

  8. He DY, Dai SM. Anti-inflammatory and immunomodulatory effects of paeonia lactiflora pall a traditional chinese herbal medicine. Front Pharmacol. 2011;2:10.

    Article  Google Scholar 

  9. Xu YJ, Mei Y, Shi XQ, Zhang YF, Wang XY, Guan L, Wang Q, Pan HF. Albiflorin ameliorates memory deficits in APP/PS1 transgenic mice via ameliorating mitochondrial dysfunction. Brain Res. 2019;1719:113–23.

    Article  CAS  Google Scholar 

  10. Fang BJ, Shen JY, Zhang H, Zhou S, Lyu CZ, Xie YQ. Albiflorin Granule significantly decreased the cholesterol gallstone formation by the regulation of insulin transduction signal. Asian Pac J Trop Med. 2016;9(9):877–81.

    Article  CAS  Google Scholar 

  11. Zhou X, Fouda S, Zeng XY, Li D, Zhang K, Xu J, Ye JM. Characterization of the therapeutic profile of albiflorin for the metabolic syndrome. Front Pharmacol. 2019;10:1151.

    Article  CAS  Google Scholar 

  12. Ma X, Song M, Yan Y, Ren G, Hou J, Qin G, Wang W, Li Z. Albiflorin alleviates cognitive dysfunction in STZ-induced rats. Aging. 2021;13(14):18287–97.

    Article  CAS  Google Scholar 

  13. Liu Y, Sun Y, Bai X, Li L. Albiflorin Alleviates Ox-LDL-Induced Human Umbilical Vein Endothelial Cell Injury through IRAK1/TAK1 Pathway. BioMed Res Int. 2022;2022:1–10.

    CAS  Google Scholar 

  14. Maracle CX, Agca R, Helder B, Meeuwsen JAL, Niessen HWM, Biessen EAL, de Winther MPJ, de Jager SCA, Nurmohamed MT, Tas SW. Noncanonical NF-κB signaling in microvessels of atherosclerotic lesions is associated with inflammation, atheromatous plaque morphology and myocardial infarction. Atherosclerosis. 2018;270:33–41.

    Article  CAS  Google Scholar 

  15. Meyerovich K, Ortis F, Cardozo AK. The non-canonical NF-κB pathway and its contribution to β-cell failure in diabetes. J Mol Endocrinol. 2018;61(2):F1–6.

    Article  CAS  Google Scholar 

  16. Baker RG, Hayden MS, Ghosh S. NF-κB, inflammation, and metabolic disease. Cell Metab. 2011;13(1):11–22.

    Article  CAS  Google Scholar 

  17. Oguiza A, Recio C, Lazaro I, Mallavia B, Blanco J, Egido J, Gomez-Guerrero C. Peptide-based inhibition of IκB kinase/nuclear factor-κB pathway protects against diabetes-associated nephropathy and atherosclerosis in a mouse model of type 1 diabetes. Diabetologia. 2015;58(7):1656–67.

    Article  CAS  Google Scholar 

  18. Zhao Y, Krishnamurthy B, Mollah ZU, Kay TW, Thomas HE. NF-κB in type 1 diabetes. Inflamm Allergy Drug Targets. 2011;10(3):208–17.

    Article  CAS  Google Scholar 

  19. Mishra M. Kowluru RA (2017) Role of PARP-1 as a novel transcriptional regulator of MMP-9 in diabetic retinopathy. Biochim Biophys Acta. 1863;7:1761–9.

    Google Scholar 

  20. Zheng L, Szabó C, Kern TS. Poly(ADP-ribose) polymerase is involved in the development of diabetic retinopathy via regulation of nuclear factor-kappaB. Diabetes. 2004;53(11):2960–7.

    Article  CAS  Google Scholar 

  21. King GL, Park K, Li Q. Selective insulin resistance and the development of cardiovascular diseases in diabetes: the 2015 Edwin Bierman award lecture. Diabetes. 2016;65(6):1462–71.

    Article  CAS  Google Scholar 

  22. Pirillo A, Catapano AL. Berberine, a plant alkaloid with lipid- and glucose-lowering properties: from in vitro evidence to clinical studies. Atherosclerosis. 2015;243(2):449–61.

    Article  CAS  Google Scholar 

  23. Zhao R, Li Q, Xiao B. Effect of Lycium barbarum polysaccharide on the improvement of insulin resistance in NIDDM rats. Yakugaku Zasshi. 2005;125(12):981–8.

    Article  CAS  Google Scholar 

  24. Chen H, Wen Y, Pan T, Xu S. Total glucosides of paeony improve complete freund’s adjuvant-induced rheumatoid arthritis in rats by inhibiting toll-like receptor 2-mediated tumor necrosis factor receptor-associated factor 6/ nuclear factor-kappa B pathway activation. J Tradit Chin Med. 2019;39(4):566–74.

    Google Scholar 

  25. Li B, He S, Liu R, Huang L, Liu G, Wang R, Yang Z, Liu X, Leng Y, Liu D, Ye C, Li Y, Chen Y, Yin H, Fang W. Total glucosides of paeony attenuates animal psoriasis induced inflammatory response through inhibiting STAT1 and STAT3 phosphorylation. J Ethnopharmacol. 2019;243(112121):26.

    Google Scholar 

  26. Lin H, Zhang W, Jiang X, Chen R, Huang X, Huang Z. Total glucosides of paeony ameliorates TNBS-induced colitis by modulating differentiation of Th17/Treg cells and the secretion of cytokines. Mol Med Rep. 2017;16(6):8265–76.

    Article  CAS  Google Scholar 

  27. Li M, Jiang A. DNA methylation was involved in total glucosides of paeony regulating ERα for the treatment of female systemic lupus erythematosus mice. J Pharmacol Sci. 2019;140(2):187–92.

    Article  CAS  Google Scholar 

  28. Wang Y, Zhang H, Du G, Cao T, Luo Q, Chen J, Chen F, Tang G. Total glucosides of paeony (TGP) inhibits the production of inflammatory cytokines in oral lichen planus by suppressing the NF-κB signaling pathway. Int Immunopharmacol. 2016;36:67–72.

    Article  Google Scholar 

  29. Zhu Q, Qi X, Wu Y, Wang K. Clinical study of total glucosides of paeony for the treatment of diabetic kidney disease in patients with diabetes mellitus. Int Urol Nephrol. 2016;48(11):1873–80.

    Article  CAS  Google Scholar 

  30. Wang K, Wu YG, Su J, Zhang JJ, Zhang P, Qi XM. Total glucosides of paeony regulates JAK2/STAT3 activation and macrophage proliferation in diabetic rat kidneys. Am J Chin Med. 2012;40(3):521–36.

    Article  CAS  Google Scholar 

  31. Su J, Zhang P, Zhang JJ, Qi XM, Wu YG, Shen JJ. Effects of total glucosides of paeony on oxidative stress in the kidney from diabetic rats. Phytomedicine. 2010;17(3–4):254–60.

    Article  CAS  Google Scholar 

  32. Shao YX, Xu XX, Li YY, Qi XM, Wang K, Wu YG, Meng XM. Paeoniflorin inhibits high glucose-induced macrophage activation through TLR2-dependent signal pathways. J Ethnopharmacol. 2016;193:377–86.

    Article  CAS  Google Scholar 

  33. Sun X, Li S, Xu L, Wang H, Ma Z, Fu Q, Qu R, Ma S. Paeoniflorin ameliorates cognitive dysfunction via regulating SOCS2/IRS-1 pathway in diabetic rats. Physiol Behav. 2017;174:162–9.

    Article  CAS  Google Scholar 

  34. Dalan R, Liu X, Goh LL, Bing S, Luo KQ. Endothelial cell apoptosis correlates with low haptoglobin concentrations in diabetes. Diab Vasc Dis Res. 2017;14(6):534–9.

    Article  CAS  Google Scholar 

  35. Ye Y, Nylander S, Birnbaum Y. Unraveling the interaction of aspirin, ticagrelor, and rosuvastatin on the progression of atherosclerosis and inflammation in diabetic mice. Cardiovasc Drugs Ther. 2017;31(5–6):489–500.

    Article  CAS  Google Scholar 

  36. Campos J, Schmeda-Hirschmann G, Leiva E, Guzmán L, Orrego R, Fernández P, González M, Radojkovic C, Zuñiga FA, Lamperti L, Pastene E, Aguayo C. Lemon grass (Cymbopogon citratus (D.C) Stapf) polyphenols protect human umbilical vein endothelial cell (HUVECs) from oxidative damage induced by high glucose, hydrogen peroxide and oxidised low-density lipoprotein. Food Chem. 2014;151:175–81.

    Article  CAS  Google Scholar 

  37. Chen Z, Morales JE, Avci N, Guerrero PA, Rao G, Seo JH, McCarty JH. The vascular endothelial cell-expressed prion protein doppel promotes angiogenesis and blood-brain barrier. Development. 2020. https://doi.org/10.1242/dev.193094.

    Article  Google Scholar 

  38. Kuchmerovska T, Guzyk M, Tykhonenko T, Yanitska L, Pryvrotska I, Diakun K. The parp-1 and bax genes as potential targets for treatment of the heart functioning impairments induced by type 1 diabetes mellitus. Endocr Regul. 2021;55(2):61–71.

    Article  Google Scholar 

  39. Li P, Wang Y, Liu X, Liu B, Wang ZY, Xie F, Qiao W, Liang ES, Lu QH, Zhang MX. Loss of PARP-1 attenuates diabetic arteriosclerotic calcification via Stat1/Runx2 axis. Cell Death Dis. 2020;11(1):22.

    Article  CAS  Google Scholar 

  40. Zakaria EM, El-Bassossy HM, El-Maraghy NN, Ahmed AF, Ali AA. PARP-1 inhibition alleviates diabetic cardiac complications in experimental animals. Eur J Pharmacol. 2016;791:444–54.

    Article  CAS  Google Scholar 

  41. Waldman M, Nudelman V, Shainberg A, Abraham NG, Kornwoski R, Aravot D, Arad M, Hochhauser E. PARP-1 inhibition protects the diabetic heart through activation of SIRT1-PGC-1α axis. Exp Cell Res. 2018;373(1–2):112–8.

    Article  CAS  Google Scholar 

  42. Hamuro M, Polan J, Natarajan M, Mohan S. High glucose induced nuclear factor kappa B mediated inhibition of endothelial cell migration. Atherosclerosis. 2002;162(2):277–87.

    Article  CAS  Google Scholar 

  43. Leng B, Zhang Y, Liu X, Zhang Z, Liu Y, Wang H, Lu M (2019) Astragaloside IV Suppresses High Glucose-Induced NLRP3 Inflammasome Activation by Inhibiting TLR4/NF-κB and CaSR. Mediators Inflamm 19 (1082497)

  44. Li Y, Sun X, Zhuang J, Wang J, Yang C. Donepezil ameliorates oxygen-glucose deprivation/reoxygenation-induced cardiac microvascular endothelial cell dysfunction through PARP1/NF-κB signaling. Mol Med Rep. 2022;25:1–9.

    Article  Google Scholar 

  45. Zhang H, Wang J, Lang W, Liu H, Zhang Z, Wu T, Li H, Bai L, Shi Q. Albiflorin ameliorates inflammation and oxidative stress by regulating the NF-κB/NLRP3 pathway in Methotrexate-induced enteritis. Int Immunopharmacol. 2022;109: 108824.

    Article  CAS  Google Scholar 

  46. Cai Z, Liu J, Bian H, Cai J. Albiflorin alleviates ovalbumin (OVA)-induced pulmonary inflammation in asthmatic mice. Am J Trans Res. 2019;11(12):7300–9.

    CAS  Google Scholar 

  47. Sun J, Li X, Jiao K, Zhai Z, Sun D. Albiflorin inhibits the formation of THP-1-derived foam cells through the LOX-1/NF-κB pathway. Minerva Med. 2019;110(2):107–14.

    Article  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Department of Rheumatology and Immunology, Zhongda Hospital Affiliated to Southeast University, Nanjing, 210009, Jiangsu, People’s Republic of China

    Rong Yang

  2. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People’s Republic of China

    Yang Yang

Authors
  1. Rong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

R Y contributed to conception and design. Y Y and R Y performed experiment. R Y and Y Y did data analysis and provided technical support. Y Y wrote the manuscript.

Corresponding author

Correspondence to Yang Yang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

NonE.

Consent to participate

NonE.

Consent for publication

Not Applicable.

Additional information

Responsible Editor: John Di Battista.

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

Yang, R., Yang, Y. Albiflorin attenuates high glucose-induced endothelial apoptosis via suppressing PARP1/NF-κB signaling pathway. Inflamm. Res. 72, 159–169 (2023). https://doi.org/10.1007/s00011-022-01666-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-022-01666-z

Keywords

Search

Navigation