Skip to main content
SpringerLink
Log in

In Silico Identification of Novel Interactions for FABP5 (Fatty Acid-Binding Protein 5) with Nutraceuticals: Possible Repurposing Approach

  • Chapter
  • First Online:
Pharmacological Properties of Plant-Derived Natural Products and Implications for Human Health

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1308))

Abstract

Fatty Acid Binding-Protein 5 (FABP5) is a cytoplasmic protein, which binds long-chain fatty acids and other hydrophobic ligands. This protein is implicated in several physiological processes including mitochondrial β-oxidation and transport of fatty acids, membrane phospholipid synthesis, lipid metabolism, inflammation and pain. In the present study, we used molecular docking tools to determine the possible interaction of FABP5 with six selected compounds retrieved form Drugbank. Our results showed that FABP5 binding pocket included 31 polar and non-polar amino acids, and these residues may be related to phosphorylation, acetylation, ubiquitylation, and mono-methylation. Docking results showed that the most energetically favorable compounds are NADH (−9.12 kcal/mol), 5′-O-({[(Phosphonatooxy)phosphinato]oxy}phosphinato)adenosine (−8.62 kcal/mol), lutein (−8.25 kcal/mol), (2S)-2-[(4-{[(2-Amino-4-oxo-1,4,5,6,7,8-hexahydro-6-pteridinyl)methyl]amino}benzoyl)amino]pentanedioate (−7.17 kcal/mol), Pteroyl-L-glutamate (−6.86 kcal/mol) and (1S,3R,5E,7Z)-9,10-Secocholesta-5,7,10-triene-1,3,25-triol (−6.79 kcal/mol). Common interacting residues of FABP5 with nutraceuticals included SER16, LYS24, LYS34, LYS40 and LYS17. Further, we used the SwissADME server to determine the physicochemical and pharmacokinetic characteristics and to predict the ADME parameters of the selected nutraceuticals after molecular analysis by docking with the FABP5 protein. Amongst all compounds, pteroyl-L-glutamate is the only one meeting the Lipinski’s rule of five criteria, demonstrating its potential pharmacological use. Finally, our results also suggest the importance of FABP5 in mediating the anti-inflammatory activity of the nutraceutical compounds.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Adhikary T, Brandt DT, Kaddatz K, Stockert J, Naruhn S, Meissner W et al (2013) Inverse PPARbeta/delta agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion. Oncogene 32(44):5241–5252. https://doi.org/10.1038/onc.2012.549

    Article  CAS  PubMed  Google Scholar 

  2. Areiza-Mazo N, Robles J, Zamudio-Rodriguez JA, Giraldez L, Echeverria V, Barrera-Bailon B et al (2018) Extracts of Physalis peruviana protect astrocytic cells under oxidative stress with rotenone. Front Chem 6:276. https://doi.org/10.3389/fchem.2018.00276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Armstrong EH, Goswami D, Griffin PR, Noy N, Ortlund EA (2014) Structural basis for ligand regulation of the fatty acid-binding protein 5, peroxisome proliferator-activated receptor beta/delta (FABP5-PPARbeta/delta) signaling pathway. J Biol Chem 289(21):14941–14954. https://doi.org/10.1074/jbc.M113.514646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Berger WT, Ralph BP, Kaczocha M, Sun J, Balius TE, Rizzo RC et al (2012) Targeting fatty acid binding protein (FABP) anandamide transporters – a novel strategy for development of anti-inflammatory and anti-nociceptive drugs. PLoS One 7(12):e50968. https://doi.org/10.1371/journal.pone.0050968

  5. Bibak B, Shakeri F, Barreto GE, Keshavarzi Z, Sathyapalan T, Sahebkar A (2019) A review of the pharmacological and therapeutic effects of auraptene. Biofactors 45(6):867–879. https://doi.org/10.1002/biof.1550

    Article  CAS  PubMed  Google Scholar 

  6. Chen J, Liu X, Zhang S, Chen J, Sun H, Zhang L, Zhang Q (2020) Molecular mechanism with regard to the binding selectivity of inhibitors toward FABP5 and FABP7 explored by multiple short molecular dynamics simulations and free energy analyses. Phys Chem Chem Phys 22(4):2262–2275. https://doi.org/10.1039/c9cp05704h

    Article  CAS  PubMed  Google Scholar 

  7. Chen W, Yi C, Jin L (2018) The role of nicotinamide adenine dinucleotide in the pathogenesis of rheumatoid arthritis: potential implications for treatment. Eur Med J 3(3):90–97

    Article  Google Scholar 

  8. Cianciulli A, Salvatore R, Porro C, Trotta T, Panaro MA (2016) Folic acid is able to polarize the inflammatory response in LPS activated microglia by regulating multiple signaling pathways. Mediat Inflamm 2016:5240127. https://doi.org/10.1155/2016/5240127

    Article  CAS  Google Scholar 

  9. Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7:42717. https://doi.org/10.1038/srep42717

    Article  PubMed  PubMed Central  Google Scholar 

  10. Danenberg PV, Gustavsson B, Johnston P, Lindberg P, Moser R, Odin E et al (2016) Folates as adjuvants to anticancer agents: chemical rationale and mechanism of action. Crit Rev Oncol Hematol 106:118–131. https://doi.org/10.1016/j.critrevonc.2016.08.001

    Article  PubMed  Google Scholar 

  11. Deutsch DG (2016) A personal retrospective: elevating anandamide (AEA) by targeting fatty acid amide hydrolase (FAAH) and the fatty acid binding proteins (FABPs). Front Pharmacol 7:370. https://doi.org/10.3389/fphar.2016.00370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Di-Poi N, Michalik L, Tan NS, Desvergne B, Wahli W (2003) The anti-apoptotic role of PPARbeta contributes to efficient skin wound healing. J Steroid Biochem Mol Biol 85(2–5):257–265. https://doi.org/10.1016/s0960-0760(03)00215-2

    Article  CAS  PubMed  Google Scholar 

  13. Floresta G, Pistara V, Amata E, Dichiara M, Marrazzo A, Prezzavento O, Rescifina A (2017) Adipocyte fatty acid binding protein 4 (FABP4) inhibitors. A comprehensive systematic review. Eur J Med Chem 138:854–873. https://doi.org/10.1016/j.ejmech.2017.07.022

    Article  CAS  PubMed  Google Scholar 

  14. Furuhashi M, Saitoh S, Shimamoto K, Miura T (2014) Fatty acid-binding protein 4 (FABP4): pathophysiological insights and potent clinical biomarker of metabolic and cardiovascular diseases. Clin Med Insights Cardiol 8(Suppl 3):23–33. https://doi.org/10.4137/CMC.S17067

    Article  PubMed  Google Scholar 

  15. Ghanaatian N, Lashgari NA, Abdolghaffari AH, Rajaee SM, Panahi Y, Barreto GE et al (2019) Curcumin as a therapeutic candidate for multiple sclerosis: molecular mechanisms and targets. J Cell Physiol 234(8):12237–12248. https://doi.org/10.1002/jcp.27965

    Article  CAS  PubMed  Google Scholar 

  16. Jurado-Coronel JC, Avila-Rodriguez M, Echeverria V, Hidalgo OA, Gonzalez J, Aliev G, Barreto GE (2016) Implication of green tea as a possible therapeutic approach for Parkinson disease. CNS Neurol Disord Drug Targets 15(3):292–300. https://doi.org/10.2174/1871527315666160202125519

    Article  CAS  PubMed  Google Scholar 

  17. Kaczocha M, Rebecchi MJ, Ralph BP, Teng YH, Berger WT, Galbavy W et al (2014) Inhibition of fatty acid binding proteins elevates brain anandamide levels and produces analgesia. PLoS One 9(4):e94200. https://doi.org/10.1371/journal.pone.0094200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Keshavarzi Z, Shakeri F, Barreto GE, Bibak B, Sathyapalan T, Sahebkar A (2019) Medicinal plants in traumatic brain injury: neuroprotective mechanisms revisited. Biofactors 45(4):517–535. https://doi.org/10.1002/biof.1516

    Article  CAS  PubMed  Google Scholar 

  19. Lee JH, Zhang Y, Zhao Z, Ye X, Zhang X, Wang H, Ye J (2017) Intracellular ATP in balance of pro- and anti-inflammatory cytokines in adipose tissue with and without tissue expansion. Int J Obes 41(4):645–651. https://doi.org/10.1038/ijo.2017.3

    Article  CAS  Google Scholar 

  20. Mazo NA, Echeverria V, Cabezas R, Avila-Rodriguez M, Tarasov VV, Yarla NS et al (2017) Medicinal plants as protective strategies against Parkinson’s disease. Curr Pharm Des 23(28):4180–4188. https://doi.org/10.2174/1381612823666170316142803

    Article  CAS  PubMed  Google Scholar 

  21. Nasri H, Baradaran A, Shirzad H, Rafieian-Kopaei M (2014) New concepts in nutraceuticals as alternative for pharmaceuticals. Int J Prev Med 5(12):1487–1499. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25709784

    PubMed  PubMed Central  Google Scholar 

  22. Ohata T, Yokoo H, Kamiyama T, Fukai M, Aiyama T, Hatanaka Y et al (2017) Fatty acid-binding protein 5 function in hepatocellular carcinoma through induction of epithelial-mesenchymal transition. Cancer Med 6(5):1049–1061. https://doi.org/10.1002/cam4.1020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ozawa Y, Sasaki M, Takahashi N, Kamoshita M, Miyake S, Tsubota K (2012) Neuroprotective effects of lutein in the retina. Curr Pharm Des 18(1):51–56. https://doi.org/10.2174/138161212798919101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Shinoda Y, Wang Y, Yamamoto T, Miyachi H, Fukunaga K (2020) Analysis of binding affinity and docking of novel fatty acid-binding protein (FABP) ligands. J Pharmacol Sci 143(4):264–271. https://doi.org/10.1016/j.jphs.2020.05.005

    Article  CAS  PubMed  Google Scholar 

  25. Singh SK, Barreto GE, Aliev G, Echeverria V (2017) Ginkgo biloba as an alternative medicine in the treatment of anxiety in dementia and other psychiatric disorders. Curr Drug Metab 18(2):112–119. https://doi.org/10.2174/1389200217666161201112206

    Article  CAS  PubMed  Google Scholar 

  26. Smathers RL, Petersen DR (2011) The human fatty acid-binding protein family: evolutionary divergences and functions. Hum Genomics 5(3):170–191. https://doi.org/10.1186/1479-7364-5-3-170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Souyoul SA, Saussy KP, Lupo MP (2018) Nutraceuticals: a review. Dermatol Ther (Heidelb) 8(1):5–16. https://doi.org/10.1007/s13555-018-0221-x

    Article  Google Scholar 

  28. Uddin MS, Al Mamun A, Kabir MT, Jakaria M, Mathew B, Barreto GE, Ashraf GM (2019) Nootropic and anti-Alzheimer’s actions of medicinal plants: molecular insight into therapeutic potential to alleviate Alzheimer’s neuropathology. Mol Neurobiol 56(7):4925–4944. https://doi.org/10.1007/s12035-018-1420-2

    Article  CAS  PubMed  Google Scholar 

  29. Wang D, Wang H, Guo Y, Ning W, Katkuri S, Wahli W et al (2006) Crosstalk between peroxisome proliferator-activated receptor delta and VEGF stimulates cancer progression. Proc Natl Acad Sci U S A 103(50):19069–19074. https://doi.org/10.1073/pnas.0607948103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Xu J, Li W, Ma J, Liu J, Sha H, Zhou S et al (2013) Vitamin D – pivotal nutraceutical in the regulation of cancer metastasis and angiogenesis. Curr Med Chem 20(33):4109–4120. https://doi.org/10.2174/09298673113209990194

  31. Yan F, Liu X, Zhang S, Su J, Zhang Q, Chen J (2018) Molecular dynamics exploration of selectivity of dual inhibitors 5M7, 65X, and 65Z toward fatty acid binding proteins 4 and 5. Int J Mol Sci 19(9):2496. https://doi.org/10.3390/ijms19092496

    Article  CAS  PubMed Central  Google Scholar 

  32. Yaribeygi H, Zare V, Butler AE, Barreto GE, Sahebkar A (2019) Antidiabetic potential of saffron and its active constituents. J Cell Physiol 234(6):8610–8617. https://doi.org/10.1002/jcp.27843

    Article  CAS  PubMed  Google Scholar 

  33. Zhang Y, Zhang J, Ren Y, Lu R, Yang L, Nie G (2020) Tracing the evolution of fatty acid-binding proteins (FABPs) in organisms with a heterogeneous fat distribution. FEBS Open Bio 10(5):861–872. https://doi.org/10.1002/2211-5463.12840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zhou Y, Elmes MW, Sweeney JM, Joseph OM, Che J, Hsu HC et al (2019) Identification of fatty acid binding protein 5 inhibitors through similarity-based screening. Biochemistry 58(42):4304–4316. https://doi.org/10.1021/acs.biochem.9b00625

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

None.

Conflict of Interests

None of the authors has a competing interest directly related to the content of this study.

Author information

Authors and Affiliations

  1. Department of Physiology, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia

    Ricardo Cabezas

  2. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  3. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  4. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  5. Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland

    Amirhossein Sahebkar

  6. Research and Development Department, Bay Pines VA Healthcare System, Bay Pines, FL, USA

    Valentina Echeverria

  7. Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia

    Janneth González Santos

  8. King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia

    Ghulam Md Ashraf

  9. Department of Biological Sciences, University of Limerick, Limerick, Ireland

    George E. Barreto

  10. Health Research Institute, University of Limerick, Limerick, Ireland

    George E. Barreto

Authors
  1. Ricardo Cabezas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amirhossein Sahebkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Valentina Echeverria
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Janneth González Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ghulam Md Ashraf
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. George E. Barreto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George E. Barreto .

Editor information

Editors and Affiliations

  1. Department of Biological Sciences, University of Limerick, Limerick, Ireland

    George E. Barreto

  2. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Cabezas, R., Sahebkar, A., Echeverria, V., Santos, J.G., Ashraf, G.M., Barreto, G.E. (2021). In Silico Identification of Novel Interactions for FABP5 (Fatty Acid-Binding Protein 5) with Nutraceuticals: Possible Repurposing Approach. In: Barreto, G.E., Sahebkar, A. (eds) Pharmacological Properties of Plant-Derived Natural Products and Implications for Human Health. Advances in Experimental Medicine and Biology, vol 1308. Springer, Cham. https://doi.org/10.1007/978-3-030-64872-5_29

Download citation

Publish with us

Policies and ethics

Search

Navigation