Skip to main content
SpringerLink
Log in

A Novel Peptide Isolated from Microalgae Isochrysis zhanjiangensis Exhibits Anti-apoptosis and Anti-inflammation in Ox-LDL Induced HUVEC to Improve Atherosclerosis

  • Original Paper
  • Published:
Plant Foods for Human Nutrition Aims and scope Submit manuscript

Abstract

In the early stage, oxidized low density lipoprotein (ox-LDL) caused atherosclerosis, followed by human umbilical vein endothelial cells (HUVEC) damage, leading to a variety of cardiovascular related diseases. This study investigated the mechanism of nonapeptide (EMFGTSSET, ETT) isolated from in vitro gastrointestinal digestion of Isochrysis zhanjiang on endothelial cell inflammation and apoptosis induced by ox-LDL in atherosclerosis. At the cellular level, the results shown that ETT inhibited the up-regulation of oxidized low-density lipoprotein receptor-1 (LOX-1) induced by ox-LDL. Furthermore, ETT inhibited the fluorescence intensity of ROS, inflammatory factors (interleukin-6, interleukin-1β, and tumor necrosis factor-α) and the expression of cell adhesion molecules (vascular cell adhesion protein 1 and intercellular cell adhesion molecule-1). In addition, it also upregulates nuclear red blood cell 2 related factor 2 (Nrf2), heme oxygenase-1 (HO -1), p-Akt, and bcl-2 levels. But down-regulated the expression of p-p65, p-IκB-α, p-p38, p-ERK, p-JNK, bax, and cleaved caspase-9/-3 (c-c-9/-3), thereby inhibited ox-LDL induction inflammation and apoptosis of atherosclerosis. Through molecular docking, it was judged that the stable interaction between ETT and LOX-1 and VCAM-1 was maintained through hydrogen bonding. These results can provide a theoretical basis for ETT as a potential substance for the prevention and treatment of atherosclerosis, and further improve the value of Isochrysis zhanjiangensis.

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.

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

Similar content being viewed by others

Data Availability

Data are available upon reasonable request.

References

  1. Barquera S, Pedroza-Tobias A, Medina C, Hernandez-Barrera L, Bibbins-Domingo K, Lozano R, Moran AE (2015) Global overview of the epidemiology of atherosclerotic cardiovascular disease. Arch Med Res 46:328–338. https://doi.org/10.1016/j.arcmed.2015.06.006

    Article  PubMed  Google Scholar 

  2. Herrington W, Lacey B, Sherliker P, Armitage J, Lewington S (2016) Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ Res 118:535–546. https://doi.org/10.1161/circresaha.115.307611

    Article  CAS  PubMed  Google Scholar 

  3. Yla-Herttuala S, Palinski W, Rosenfeld ME, Parthasarathy S, Carew TE, Butler S, Witztum JL, Steinberg D (1989) Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. J Clin Invest 84:1086–1095. https://doi.org/10.1172/jci114271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pirillo A, Norata GD, Catapano AL (2013) LOX-1, OxLDL, and atherosclerosis. Mediat Inflamm 2013:152786. https://doi.org/10.1155/2013/152786

    Article  CAS  Google Scholar 

  5. Sawamura T, Kume N, Aoyama T, Moriwaki H, Hoshikawa H, Aiba Y, Tanaka T, Miwa S, Katsura Y, Kita T, Masaki T (1997) An endothelial receptor for oxidized low-density lipoprotein. Nature 386:73–77. https://doi.org/10.1038/386073a0

    Article  CAS  PubMed  Google Scholar 

  6. Mitra S, Goyal T, Mehta JL (2011) Oxidized LDL, LOX-1 and atherosclerosis. Cardiovasc Drugs Ther 25:419–429. https://doi.org/10.1007/s10557-011-6341-5

    Article  CAS  PubMed  Google Scholar 

  7. Duan H, Zhang Q, Liu J, Li R, Wang D, Peng W, Wu C (2021) Suppression of apoptosis in vascular endothelial cell, the promising way for natural medicines to treat atherosclerosis. Pharmacol Res 168:105599. https://doi.org/10.1016/j.phrs.2021.105599

    Article  CAS  PubMed  Google Scholar 

  8. Singh M, Bedi US (2013) Is atherosclerosis regression a realistic goal of statin therapy and what does that mean? Curr Atheroscler Rep 15:294. https://doi.org/10.1007/s11883-012-0294-4

    Article  CAS  PubMed  Google Scholar 

  9. Thompson PD, Panza G, Zaleski A, Taylor B (2016) Statin-associated side effects. J Am Coll Cardiol 67:2395–2410. https://doi.org/10.1016/j.jacc.2016.02.071

    Article  CAS  PubMed  Google Scholar 

  10. Duan L, Xiong X, Hu J, Liu Y, Li J, Wang J (2017) Panax notoginseng saponins for treating coronary artery disease: a functional and mechanistic overview. Front Pharmacol 8:00702. https://doi.org/10.3389/fphar.2017.00702

    Article  CAS  Google Scholar 

  11. Khavari F, Saidijam M, Taheri M, Nouri F (2021) Microalgae: therapeutic potentials and applications. Mol Biol Rep 48:4757–4765. https://doi.org/10.1007/s11033-021-06422-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rizwan M, Mujtaba G, Memon SA, Lee K, Rashid N (2018) Exploring the potential of microalgae for new biotechnology applications and beyond: a review. Renew Sust Energy Rev 92:394–404. https://doi.org/10.1016/j.rser.2018.04.034

    Article  Google Scholar 

  13. Bonfanti C, Cardoso C, Afonso C, Matos J, Garcia T, Tanni S, Bandarra NM (2018) Potential of microalga Isochrysis galbana: bioactivity and bioaccessibility. Algal Res 29:242–248. https://doi.org/10.1016/j.algal.2017.11.035

    Article  Google Scholar 

  14. Chen J, Tan L, Li C, Zhou C, Hong P, Sun S, Qian ZJ (2020) Mechanism analysis of a novel angiotensin-I-converting enzyme inhibitory peptide from Isochrysis zhanjiangensis microalgae for suppressing vascular injury in human umbilical vein endothelial cells. J Agric Food Chem 68:4411–4423. https://doi.org/10.1021/acs.jafc.0c00925

    Article  CAS  PubMed  Google Scholar 

  15. Basri EM, Maznah WOW (2017) Differential growth and biochemical composition of photoautotrophic and heterotrophic Isochrysis maritima: evaluation for use as aquaculture feed. J Appl Phycol 29:1159–1170. https://doi.org/10.1007/s10811-017-1054-1

    Article  CAS  Google Scholar 

  16. Yu SJ, Hu H, Zheng H, Wang YQ, Pan SB, Zeng RJ (2019) Effect of different phosphorus concentrations on biodiesel production from Isochrysis zhangjiangensis under nitrogen sufficiency or deprivation condition. Appl Microbiol Biotechnol 103:5051–5059. https://doi.org/10.1007/s00253-019-09814-y

    Article  CAS  PubMed  Google Scholar 

  17. Chen MF, Zhang YY, He MD, Li CY, Zhou CX, Hong PZ, Qian ZJ (2019) Antioxidant peptide purified from enzymatic hydrolysates of Isochrysis zhanjiangensis and its protective effect against ethanol induced oxidative stress of HepG2 cells. Biotechnol Bioprocess Eng 24:308–317. https://doi.org/10.1007/s12257-018-0391-5

    Article  CAS  Google Scholar 

  18. Wong FC, Xiao J, Wang S, Ee KY, Chai TT (2020) Advances on the antioxidant peptides from edible plant sources. Trends Food Sci Technol 99:44–57. https://doi.org/10.1016/j.tifs.2020.02.012

    Article  CAS  Google Scholar 

  19. Qian ZJ, Chen MF, Chen J, Zhang Y, Zhou C, Hong P, Yang P (2021) Intracellular ethanol-mediated oxidation and apoptosis in HepG2/CYP2E1 cells impaired by two active peptides from seahorse (Hippocampus kuda bleeler) protein hydrolysates via the Nrf2/HO-1 and akt pathways. Food Sci Nutr 9:1584–1602. https://doi.org/10.1002/fsn3.2133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Li X, Ma J, Wang J (2015) Cytotoxicity, oxidative stress, and apoptosis in HepG2 cells induced by ionic liquid 1-methyl-3-oct-ylimidazolium bromide. Ecotoxicol Environ Saf 120:342–348. https://doi.org/10.1016/j.ecoenv.2015.06.018

    Article  CAS  PubMed  Google Scholar 

  21. Zhang L, Zhou G, Song W, Tan X, Guo Y, Zhou B, Jing H, Zhao S, Chen L (2012) Pterostilbene protects vascular endothelial cells against oxidized low-density lipoprotein-induced apoptosis in vitro and in vivo. Apoptosis 17:25–36. https://doi.org/10.1007/s10495-011-0653-6

    Article  CAS  PubMed  Google Scholar 

  22. Janeesh PA, Abraham A (2013) Amelioration of cholesterol induced atherosclerosis by normalizing gene expression, cholesterol profile and antioxidant enzymes by vigna unguiculata. Plant Foods Hum Nutr 68:118–123. https://doi.org/10.1007/s11130-013-0345-1

    Article  CAS  PubMed  Google Scholar 

  23. Chapple SJ, Siow RCM, Mann GE (2012) Crosstalk between Nrf2 and the proteasome: therapeutic potential of Nrf2 inducers in vascular disease and aging. Int J Biochem Cell Biol 44:1315–1320. https://doi.org/10.1016/j.biocel.2012.04.021

    Article  CAS  PubMed  Google Scholar 

  24. Peng S, Hou Y, Yao J, Fang J (2017) Activation of Nrf2-driven antioxidant enzymes by cardamonin confers neuroprotection of PC12 cells against oxidative damage. Food Funct 8:997–1007. https://doi.org/10.1039/c7fo00054e

    Article  CAS  PubMed  Google Scholar 

  25. Schipper HM, Song W, Tavitian A, Cressatti M (2019) The sinister face of heme oxygenase-1 in brain aging and disease. Prog Neurobiol 172:40–70. https://doi.org/10.1016/j.pneurobio.2018.06.008

    Article  CAS  PubMed  Google Scholar 

  26. Wang Y, Dong L, Li J, Luo M, Shang B (2017) Pentoxifylline induces apoptosis of HepG2 cells by reducing reactive oxygen species production and activating the MAPK signaling. Life Sci 183:60–68. https://doi.org/10.1016/j.lfs.2017.05.029

    Article  CAS  PubMed  Google Scholar 

  27. Zhang Z, Ren Z, Chen S, Guo X, Liu F, Guo L, Mei N (2018) ROS generation and JNK activation contribute to 4-methoxy-TEMPO-induced cytotoxicity, autophagy, and DNA damage in HepG2 cells. Arch Toxicol 92:717–728. https://doi.org/10.1007/s00204-017-2084-9

    Article  CAS  PubMed  Google Scholar 

  28. Fares R, Bazzi S, Baydoun SE, Abdel-Massih RM (2011) The antioxidant and anti-proliferative activity of the lebanese olea europaea extract. Plant Foods Hum Nutr 66:58–63. https://doi.org/10.1007/s11130-011-0213-9

    Article  PubMed  Google Scholar 

  29. Zhang X, Tang N, Hadden TJ, Rishi AK (2011) Akt, FoxO and regulation of apoptosis. BBA-Mol Cell Res 1813:1978–1986. https://doi.org/10.1016/j.bbamcr.2011.03.010

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The research was funded by the 2020 Shenzhen International Scientific and Technological Cooperation R&D Project (GJHZ20190823111601682) and Guangdong Basic and Applied Basic Research Foundation (2020A1515011075). The supported by the Development Project about Marine Economy Demonstration of Zhanjiang City (XM-202008-01B1) and Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang, ZJW-2019-07).

Author information

Authors and Affiliations

  1. College of Food Science and Technology, School of Chemistry and Environment, Shenzhen Institute of Guangdong Ocean University, Zhanjiang 524088 and Shenzhen 518114, China

    Yu Pei, Yi Lui, Shengxuan Cai, Chunxia Zhou, Pengzhi Hong & Zhong-Ji Qian

  2. Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang, 524025, China

    Chunxia Zhou, Pengzhi Hong & Zhong-Ji Qian

Authors
  1. Yu Pei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yi Lui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shengxuan Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chunxia Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pengzhi Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhong-Ji Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Pengzhi Hong or Zhong-Ji Qian.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

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

Yu Pei and Yi Lui have contributed equally to this work and share first authorship.

Supplementary Information

Below is the link to the electronic supplementary material.

ESM 1

(DOC 79.5 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pei, Y., Lui, Y., Cai, S. et al. A Novel Peptide Isolated from Microalgae Isochrysis zhanjiangensis Exhibits Anti-apoptosis and Anti-inflammation in Ox-LDL Induced HUVEC to Improve Atherosclerosis. Plant Foods Hum Nutr 77, 181–189 (2022). https://doi.org/10.1007/s11130-022-00965-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11130-022-00965-4

Keywords

Search

Navigation