Skip to main content
SpringerLink
Log in

Atheroprotective effect of novel peptides from Porphyridium purpureum in RAW 264.7 macrophage cell line and its molecular docking study

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

Objective

To explore the atherogenic foam cell prevention efficiency of two dipeptides purified from Porphyridium purpureum on RAW 264.7 cell line and to study its molecular interaction through molecular docking.

Result

P. purpureum consists of 29.9% protein and 2.98% phycoerythrin on a dry weight basis. The two dipeptides namely of Histidine–Glutamic acid (HE) and Glycine–Proline (GP) isolated from the total protein and purified phycoerythrin of P. purpureum respectively, were evaluated for atherogenic foam cell prevention capacity in RAW 264.7 cell line. The IC5O values of peptides were found to be 91.2 ± 1.81 µg/ml (GP), 103.3 ± 4.8 µg/ml (HE) in MTT assay. The two peptides reduce the foam cell formation, intracellular lipid accumulation (cholesterol and triglycerides) and the secretion of TNF-α and IL-6 which are inflammatory cytokines in RAW 264.7 cell line at non-cytotoxic concentrations. A molecular interaction study proposed the binding pose for GP and HE peptides targeting the scavenging receptors CD36, SRA1, and Map Kinase p38 (a protein mediator).

Conclusions

The cell line and molecular docking study indicated that among the two dipeptides, peptide GP has the highest atherogenic foam cell prevention efficiency.

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

  • Aditya Rao SJ, Jeevitha B, Smitha R, Ramesh CK, Paramesha M, Jamuna KS (2015) Wound healing activity from the leaf extracts of Morus laevigata and in silico binding studies from its isolates with gsk 3-β. Int J Res Dev Pharm Life Sci 4:1686–1696

    CAS  Google Scholar 

  • Bermejo R, Talavera EM, Del Valle C, Alvarez-Pez JM (2000) C-phycocyanin incorporated into reverse micelles: a fluorescence study. Coll Surf B Biointerf 18:51–59

    Article  CAS  Google Scholar 

  • De Vivo M, Masetti M, Bottegoni G, Cavalli A (2016) Role of molecular dynamics and related methods in drug discovery. J Med Chem 59:4035–4061

    Article  CAS  PubMed  Google Scholar 

  • Gasteiger J, Marsili M (1980) Iterative partial equalization of orbital electro negativity—a rapid access to atomic charges. Tetrahedron 36:3219–3228

    Article  CAS  Google Scholar 

  • Gioia D, Bertazzo M, Recanatini M, Masetti M, Cavalli A (2017) Dynamic docking: a paradigm shift in computational drug discovery. Mol Rev. https://doi.org/10.3390/molecules22112029

    Article  Google Scholar 

  • Greenspan P, Yu H, Mao F, Gutman RL (1997) Cholesterol deposition in macrophages: foam cell formation mediated by cholesterol-enriched oxidized low density lipoprotein. J Lipid Res 38:101–109

    CAS  PubMed  Google Scholar 

  • Hartmann R, Meisel H (2007) Food-derived peptides with biological activity: from research to food applications. Curr Opin Biotechnol 18:163–169

    Article  CAS  PubMed  Google Scholar 

  • Heinecke JW (1999) Mechanisms of oxidative damage by myeloperoxidase in atherosclerosis and other inflammatory disorders. J Lab Clin Med 133:321–325

    Article  CAS  PubMed  Google Scholar 

  • Heo SJ, Jeon YJ (2008) Radical scavenging capacity and cytoprotective effect of enzymatic digests of Ishigeo kamurae. J Appl Phycol 20:1087–1095

    Article  Google Scholar 

  • Hou YC, Janczuk A, Wang PG (1999) Current trends in the development of nitric oxide donors. Curr Pharm Des 5:417–419

    CAS  PubMed  Google Scholar 

  • Huang J, Chen B, You W (2005) Studies on separation of extracellular polysaccharide of Porphyridium Cruentum and its anti-HBV in vitro. Chin J Mar Drugs 24:18–21

    CAS  Google Scholar 

  • Jimsheena VK, Gowda LR (2010) Arachin derived peptides as selective angiotensin I-converting enzyme (ACE) inhibitors: structure–activity relationship. Peptides 31:1165–1176

    Article  CAS  PubMed  Google Scholar 

  • Jones RE, Speer HL, Kury W (1963) Studies on the growth of the red alga Porphyridium cruentum. Physiol Plant 16:636–643

    Article  CAS  Google Scholar 

  • Jugdutt BI (2012) Prevention of heart failure in the elderly: when, where and how to begin. Heart Fail Rev 17:531–544

    Article  PubMed  Google Scholar 

  • Kalayoglu MV, Byrne GI (1998) Induction of macrophage foam cell formation by Chlamydia pneumonia. J Infect Dis 177:725–729

    Article  CAS  PubMed  Google Scholar 

  • Kavitha MD, Kathiresan S, Bhattacharya Sila, Sarada R (2016a) Culture media optimization of Porphyridium purpureum: production potential of biomass, total lipids, arachidonic and eicosapentaenoic acid. J Food Sci Technol 53:2270–2278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kavitha MD, Seema Shree MH, Vidyashankar S, Sarada R (2016b) Acute and subchronic safety assessment of Porphyridium purpureum biomass in the rat model. J Appl Phycol 28:1071–1083

    Article  CAS  Google Scholar 

  • Khalid R (2007) Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging 2:219–236

    Google Scholar 

  • Kim KN, Heo SJ, Song CB, Lee J, Heo MS, Yeo IK, Kang KA, Hyun JW, Jeon YJ (2006) Protective effect of Ecklonia cava enzymatic extracts on hydrogen peroxide-induced cell damage. Process Biochem 41:2393–2401

    Article  CAS  Google Scholar 

  • Korhonen H (2009) Milk-derived bioactive peptides: from science to applications. J Funct Foods 1:177–187

    Article  CAS  Google Scholar 

  • Kzhyshkowska J, Neyen C, Gordon S (2012) Role of macrophage scavenger receptors in atherosclerosis. Immunobiol 217:492–502

    Article  CAS  Google Scholar 

  • Lee SH (1992) Antioxidative activity of browning reaction products isolated from storage-aged orange juice. J Agric Food Chem 40:550–552

    Article  CAS  Google Scholar 

  • Lee MY, Yuk JE, Kwon OK, Zuonin B (2012) Inhibits lipopolysaccharide-induced inflammation via downregulation of the ERK1/2 and JNK pathways in RAW264. 7 macrophages. Evid Based Complement Alternat Med 65:1–8

    Google Scholar 

  • Lourenco SO, Barbarino E, De-Paula JC, Da S, Pereira LO, Marquez UML (2002) Amino acid composition, protein content and calculation of nitrogen to protein conversion factors for 19 tropical seaweeds. Phycol Res 50:233–241

    Article  CAS  Google Scholar 

  • Marcocci L, Maguire JJ, Droylefaix MT, Packer L (1994) The nitric oxide-scavenging properties of Ginkgo biloba extract EGb 761. Biochem Biophys Res Commun 201:748–755

    Article  CAS  PubMed  Google Scholar 

  • Mendez AJ, Oram JF, Bierman EL (1991) Protein kinase C as a mediator of high density lipoprotein receptor-dependent efflux of intracellular cholesterol. J Bio Chem 266:10104–10111

    CAS  Google Scholar 

  • Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1999) Automated docking using a Lamarckian Genetic algorithm and empirical binding free energy function. J Comput Chem 19:1639–1662

    Article  Google Scholar 

  • Neuhaus FC (2011) Role of the omega loop in specificity determination in sub site 2 of the d-alanine: d-alanine (d-lactate) ligase from Leuconostoc mesenteroides: a molecular docking study. J Mol Graph Model 30:31–37

    Article  CAS  PubMed  Google Scholar 

  • Oktyabrsky O, Smirnova G (2007) Redox regulation of cellular functions. Biochem Mosc 72:132–145

    Article  CAS  Google Scholar 

  • Orrego R, Leiva E, Cheel J (2009) Inhibitory effect of three C-glycosyl flavonoids from Cymbopogon citratus (lemongrass) on human low density lipoprotein oxidation. Molecules 14:3906–3913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paramesha M, Ramesh CK, Krishna V, Swamy HMK, AdityaRao SJ, Hoskerri J (2015) Effect of dehydroabietyl amine in angiogenesis and GSK3-β inhibition during wound healing activity in rats. Med Chem Res 24:295–303

    Article  CAS  Google Scholar 

  • Patel D, Desai S, Gajaria T (2013) Coriandrum sativum l. Seed extract mitigates lipotoxicity in RAW 264.7 cells and prevents atherogenic changes in rats. Excli J 12:313–334

    PubMed  PubMed Central  Google Scholar 

  • Priyanto AD, Doerksen RJ, Chang CI, Sung WC, Widjanarko SB, Kusnadi J, Lin YC, Wang TC, Hsu JL (2015) Screening, discovery, and characterization of angiotensin-I converting enzyme inhibitory peptides. Derived from proteolytic hydrolysate of bitter melon seed proteins. J Proteom 128:424–435

    Article  CAS  Google Scholar 

  • Raghavendra S, Aditya Rao SJ, Kumar V, Ramesh CK (2015) Multiple ligand simulataneous docking (MLSD): a novel approach to study the effect of inhibition on substrate binding to PPO. Comput Bio Chem. https://doi.org/10.1016/j.ijom.2015.09.008

    Article  Google Scholar 

  • Roman RB, Alvarez-Pez JM, Fernandez FGA, Molina Grima E (2002) Recovery of pure B-phycoerythrin from the microalga Porphyridium cruentum. J Biotechnol 93:73–85

    Article  Google Scholar 

  • Samarakoon K, Jeon You-Jin (2012) Bio-functionalities of proteins derived from marine algae: a review. Food Res Intl 48:948–960

    Article  CAS  Google Scholar 

  • Sanner MF, Olson AJ, Spehner J (1996) Reduced surface: an efficient way to compute molecular surfaces. Biopolymers 38:305–320

    Article  CAS  PubMed  Google Scholar 

  • Schwartz CJ, Valente AJ, Sprague EA, Kelley JL, Nerem RM (1991) The pathogenesis of atherosclerosis: an overview. Clin Cardiol 14:1–16

    Article  Google Scholar 

  • Sekar S, Chandramohan M (2008) Phycobiliproteins as a commodity: trends in applied research, patents, and commercialization. Appl Phycol 20:113–136

    Article  Google Scholar 

  • Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O’Brien E, Ostergren J (2003) ASCOT investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicenter randomised controlled trial. Lancet 361:1149–1158

    Article  CAS  Google Scholar 

  • Sheih IC, Tony JF, Wub Tung-Kung (2009) Isolation and characterisation of a novel angiotensin I-converting enzyme (ACE) inhibitory peptide from the algae protein waste. Food Chem 115:279–284

    Article  CAS  Google Scholar 

  • Simons RK, Junger WG, Loomis WH, Hoyt DB (1996) Acute lung injury in endotoxemic rats is associated with sustained circulating IL-6 levels and intrapulmonary CINC activity and neutrophil recruitment—role of circulating TNF-alpha and IL-beta? Shock 6:39–45

    Article  CAS  PubMed  Google Scholar 

  • Suetsuna K (1998) Purification and identification of angiotensin I-converting enzyme inhibitors from the red alga Porphyra yezoensis. J Mar Biotechnol 6:163–167

    CAS  PubMed  Google Scholar 

  • Suetsuna K, Nakano T (2000) Identification of an antihypertensive peptide from peptic digest of wakame (Undaria pinnatifida). J Nutr Biochem 11:450–454

    Article  CAS  PubMed  Google Scholar 

  • Tchernov AA, Minkova KM, Houbavenska NB, Kovacheva NG (1999) Purification of phycobiliproteins from Nostoc sp. by aminohexyl-sepharose chromatography. J Biotechnol 69:69–73

    Article  CAS  Google Scholar 

  • Tripathi SN, Kapoor S, Shrivastave A (2007) Extraction and purification of an unusual phycoerythrin in a terrestrial desiccation tolerant cyanobacterium Lyngbya arboricola. J Appl Phycol 19:441–447

    Article  CAS  Google Scholar 

  • Wasaporn C, Jurriaan M, Robert AMV, Huub FJS, Harry JW (2010) Transcription profiles of LPS-stimulated THP-1 monocytes and macrophages: a tool to study inflammation modulating effects of food-derived compounds. Food Funct 1:254–261

    Article  CAS  Google Scholar 

  • White RC, Brock TA, Chang LY, Crapo J, Briscoe P, Ku D, Bradley WA, Gianturco SH, Gore J, Freeman BA (1994) Superoxide and peroxynitrite in atherosclerosis. Proc Natl Acad Sci USA 91:1044–1048

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

The authors thank Director, CSIR-CFTRI for providing facilities to carry out the study. MDK acknowledge the ICMR, for research fellowship grants. Authors thank Dr. Uma Manjappara for her support in synthetic peptide synthesis.

Author information

Authors and Affiliations

  1. Department of Plant Cell Biotechnology, Central Food Technological Research Institute, Mysore, 570020, India

    Mysore Doddaiah Kavitha, Karekal Girinur Mallikarjun Gouda, Nandini Prasad Shetty & Ravi Sarada

  2. Molecular Biomedicine Laboratory, Department of P.G. Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga, 577201, India

    Shimoga Janakirama Aditya Rao

  3. Department of Lipidomics, Central Food Technological Research Institute, Mysore, 570020, India

    Talkad Shivashankara Shilpa

Authors
  1. Mysore Doddaiah Kavitha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karekal Girinur Mallikarjun Gouda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shimoga Janakirama Aditya Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Talkad Shivashankara Shilpa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nandini Prasad Shetty
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ravi Sarada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ravi Sarada.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kavitha, M.D., Gouda, K.G.M., Aditya Rao, S.J. et al. Atheroprotective effect of novel peptides from Porphyridium purpureum in RAW 264.7 macrophage cell line and its molecular docking study. Biotechnol Lett 41, 91–106 (2019). https://doi.org/10.1007/s10529-018-2621-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-018-2621-5

Keywords

Search

Navigation