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Optimization of protein extraction from sesame seeds by using response surface methodology RSM

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Abstract

Purpose

This study aimed to optimize the extraction condition for protein from sesame seed by-product and its characterization.

Methods

Using response surface methodology and central composite rotatable design, the protein was extracted from sesame seed. Physicochemical properties of sesame seed protein extract were investigated. The antioxidant activity was evaluated using the DPPH, ABTS, FRAP, and TAC assays. HPLC was performed to characterize the protein profile.

Results

The optimized conditions obtained with 40/1 (v/w) solvent/solid ratio, 21 h extraction time, and 50 °C extraction temperature lead to the maximum protein yield of 80.57% and an IC50 value of about 0.002 mg/mL with DPPH, which is well in close agreement with the value predicted by the model (83.06% and 0.015 mg/mL). The proximate analyses of the extract indicated that it contained 80.57% protein, 1.47% fat, 78.03 µg GAE/10 µL of total phenolic content, and 52.97 µg QE/10 µL flavonoids. Antioxidant activity of defatted sesame seed protein extract showed high activity (DPPH IC50 = 0.012 mg/mL, ABTS IC50 = 0.011 mg/mL, FRAP = 0.457, and TAC = 72.4%). The extract had also a crucial amino acid profile that could be considered bioactive peptides.

Conclusion

The findings suggest that sesame seeds are rich in protein, phenolics, flavonoids, and nutrients, and display notable antioxidant capabilities. This indicates that including sesame seeds in one’s diet might offer protective benefits against various diseases.

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References  

  1. Kopsahelis N, Kachrimanidou V. Advances in food and byproducts processing towards a sustainable bioeconomy. Foods. 2019;2019(8):425. https://doi.org/10.3390/books978-3-03921-753-3.

    Article  Google Scholar 

  2. Thai-Chai T-T, Tan Y-N, Ee K-Y, Xiao J, Wong F. C (2019) Seeds, fermented foods, and agricultural by-products as sources of plant-derived antibacterial peptides. Crit Rev Food Sci Nutr. 2019;59:S162–77. https://doi.org/10.1080/10408398.2018.1561418.

    Article  CAS  Google Scholar 

  3. Bah CSF, Carne A, McConnell MA, Mros S, Bekhit AEDA. Production of bioactive peptide hydrolysates from deer, sheep, pig and cattle red blood cell fractions using plant and fungal protease preparations. Food Chem. 2016;202:458–66. https://doi.org/10.1016/j.foodchem.2016.02.020.

    Article  CAS  PubMed  Google Scholar 

  4. Zamora-Sillero J, Gharsallaoui A, Prentice C. Peptides from fish by-product protein hydrolysates and its functional properties: an overview. Mar Biotechnol. 2018;20:118–30. https://doi.org/10.1007/s10125-018-9799-3.

    Article  CAS  Google Scholar 

  5. Xinyi W, Ai X, Zhu Z, Zhang M, Pan F, Zichen Yang Ou, Wang LZ, Zhao L. Pancreatic lipase inhibitory effects of peptides derived from sesame proteins: In silico and in vitro analyses. Int. J. Biol. Macromol. Volume 222. Part A. 2022;2022:1531–7. https://doi.org/10.1016/j.ijbiomac.2022.09.259.

    Article  CAS  Google Scholar 

  6. Fan H, Liu H, Zhang Y, Zhang S, Liu T, Wang D. Review on plant-derived bioactive peptides: biological activities, mechanism of action and utilizations in food development. J Future Foods. 2022;2(2):143–59. https://doi.org/10.1016/j.futfo.2022.03.003.

    Article  Google Scholar 

  7. Sá AGA, Pacheco MTB, Moreno YMF, Carciofi BAM. Cold-pressed sesame seed meal as a protein source: effect of processing on the protein digestibility, amino acid profile, and functional properties. J Food Compos Anal. 2022;111:104634. https://doi.org/10.1016/j.jfca.2022.104634.

    Article  CAS  Google Scholar 

  8. Sarkis JR, Michel I, Tessaro IC, Marczak LDF. Optimization of phenolics extraction from sesame seed cake. Sep Purif Technol. 2014;2014(122):506–14. https://doi.org/10.1016/j.seppur.2013.11.036.

    Article  CAS  Google Scholar 

  9. Shu Z, Liu L, Geng P, Liu J, Shen W, Tu M. Sesame cake hydrolysates improved spatial learning and memory of mice. Food Biosci. 2019;31:100440. https://doi.org/10.1016/j.fbio.2019.100440.

    Article  CAS  Google Scholar 

  10. Shima AN, Ahemen SA, Acham IO. Effect of addition of tigernut and defatted sesame flours on the nutritional composition and sensory quality of the wheat based bread. Ann Food Sci Technol. 2019;20(1):15–23 (https://www.researchgate.net/publication/334057206http://www.afst.valahia.ro/images/documente/2019/issue1/I.3_Shima.pdf).

    CAS  Google Scholar 

  11. Ahemen SA, Shima AN, Acham IO. Evaluation of the physical, functional and microbiological properties of composite bread from wheat, tigernut and defatted sesame flour blends. Asian Food Sci J. 2018;4(2):1–10. https://doi.org/10.9734/AFSJ/2018/43894.

    Article  Google Scholar 

  12. Karnika P, Naik SN, Durai Vadivel P, Hariprasad DG, Saravanadevi S. Utilization of defatted sesame cake in enhancing the nutritional and functional characteristics of biscuits. J Food Process Preserv. 2018. https://doi.org/10.1111/jfpp.13751.

    Article  Google Scholar 

  13. Martínez E, García-Martínez R, Álvarez-Ortí M, Rabadán A, Pardo-Giménez A, Pardo JE. Elaboration of gluten-free cookies with defatted seed flours: effects on technological, nutritional, and consumer aspects. Foods. 2021;10(10):1213. https://doi.org/10.3390/foods10061213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Qin X, Samilyk M, Luo Y, Sokolenko V. Influence of sesame flour on physicochemical properties of sour milk drinks. East Eur J Enterp. 2021;3(11):6–16. https://doi.org/10.15587/1729-4061.2021.234752.

    Article  CAS  Google Scholar 

  15. De Lamo B, Gomez M. Bread Enrichment with oilseeds. A review. Foods. 2018;7(11):191. https://doi.org/10.3390/foods7110191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Qin P, Wang T, Luo Y. A review on plant-based proteins from soybean: Health benefits and soy product development. J Agric Res. 2022;7:100265. https://doi.org/10.1016/j.jafr.2021.100265.

    Article  CAS  Google Scholar 

  17. Fasuan TO, Gbadamosi SO, Omobuwajo TO. Characterization of protein isolate from Sesamum indicum seed: in vitro protein digestibility, amino acid profile, and some functional properties. Food Sci Nutr. 2018;6:1715–23. https://doi.org/10.1002/fsn3.743.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Liao J, Zheng N, Qu B. An improved ultrasonic-assisted extraction method by optimizing the ultrasonic frequency for enhancing the extraction efficiency of lycopene from tomatoes. Food Anal Meth. 2016;9:2288–98. https://doi.org/10.1007/s12161-016-0419-4.

    Article  Google Scholar 

  19. Yan Yl, Yu Ch, Chen J, Li Xx, Wang W, Li Sq. Ultrasonic-assisted extraction optimized by response surface methodology, chemical composition and antioxidant activity of polysaccharides from Tremella mesenterica. Carbohydr Polym. 2011;83:217–24. https://doi.org/10.1016/j.carbpol.2010.07.045.

    Article  CAS  Google Scholar 

  20. Pan H, Zhang Q, Cui K, Chen G, Liu X, Wang L. Optimization of extraction of linarin from Flos chrysanthemi indici by response surface methodology and artificial neural network. J Sep Sci. 2017;40:2062–70. https://doi.org/10.1002/jssc.201601259.

    Article  CAS  PubMed  Google Scholar 

  21. Manamperi WA, Wiesenborn DP, Chang SK, Pryor SW. Effects of protein separation conditions on the functional and thermal properties of canola protein isolates. J Food Sci. 2011;76(3):E266–73. https://doi.org/10.1111/j.1750-3841.2011.02087.x.

    Article  CAS  PubMed  Google Scholar 

  22. Dench JE, Rivas RN, Caygill JC. Selected functional properties of sesame (Sesamum indicum L.) flour and two protein isolates. J Sci Food Agric. 1981;32(6):557–64.

    Article  Google Scholar 

  23. Rivas RN, Dench JE, Caygill JC. Nitrogen extractability of sesame (Sesamum indicum L.) seed and the preparation of two protein isolates. J Sci Food Agric. 1981;32(6):565–71.

    Article  Google Scholar 

  24. Inyang UE, Iduh AO. Influence of pH and salt concentration on protein solubility, emulsifying and foaming properties of sesame protein concentrate. JAOCS. 1996;73(12):1663–7.

    Article  CAS  Google Scholar 

  25. Onsaard E, Pomsamud P, Audtum P. Functional properties of sesame protein concentrates from sesame meal. Asian J Food Agro-Ind. 2010;3(4):420–31 (ISSN 1906-3040).

    Google Scholar 

  26. Cano-Medina A, Jiménez-Islas H, Dendooven L, Herrera RP, González-Alatorre G, EscamillaSilva EM. Emulsifying and foaming capacity and emulsion and foam stability of sesame protein concentrates. Food Res Int. 2011;44(3):684–92.

    Article  CAS  Google Scholar 

  27. Tunde-Akintunde TY, Oke MO, Akintunde BO. Sesame seed. In: Uduak GA, editor. Oilseeds. Croatia: InTech Publishers; 2012. (http://www.intechopen.com/books/oilseeds/sesameseed).

    Google Scholar 

  28. Onsaard E. Sesame proteins. Int Food Res J. 2012;19(4):1287–95.

    CAS  Google Scholar 

  29. Latif S, Anwar F. Effect of aqueous enzymatic processes on sunflower oil quality. JAOCS. 2009;86(4):393–400.

    Article  CAS  Google Scholar 

  30. Peng Y, Khaled U, Al-Rashed AAAA, Meer R, Goodarzi M. Sarafraz MM (2020) Potential application of response surface methodology (RSM) for the prediction and optimization of thermal conductivity of aqueous CuO (II) nano fluid: a statistical approach and experimental validation. Physica. 2020;554:124353. https://doi.org/10.1016/j.physa.2020.124353.

    Article  CAS  Google Scholar 

  31. Deepanshu G, Snehasis C, Gokhale JS. Optimizing the extraction of protein from Prosopis cineraria seeds using response surface methodology and characterization of seed protein concentrate. Food Sci Technol. 2020;117(2020):108630. https://doi.org/10.1016/j.lwt.2019.108630.

    Article  CAS  Google Scholar 

  32. Melo D, Avarez-Orti M, Nunes MA, Costa AS, Machado S, Alves RC, Pardo JE. Whole or defatted sesame seed (Sesamum indicum L.): the effect of cold pressing on oil and cake quality. Foods. 2021;10:2108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lee N, Shin S, Chung HJ, Kim DK, Lim JM, Park H, Oh HJ. Improved quantification of protein in vaccines containing aluminum hydroxide by simple modification of the Lowry method. Vaccine. 2015;33:5031–4. https://doi.org/10.1016/j.vaccine.2015.08.004.

    Article  CAS  PubMed  Google Scholar 

  34. AOAC. Official methods of analysis. 15th ed. Washington: Association of Official Analytical Chemists; 1990.

    Google Scholar 

  35. Quero-Jiménez PC, Montenegro ON, Sosa R, de la Torre JB, Valero Acosta J, López Pérez D, Santana Rodríguez A, Ramos Méndez R, Calvo Alonso A, Corrales AJ, Broche Hernández N. Total carbohydrates concentration evaluation in products of microbial origin. Afinidad -Barcelona-. 2019;76(587):83–90.

    Google Scholar 

  36. Laouini SE, Kelef A, Ouahrani MR. Free radicals scavenging activity and phytochemical composition of astermisia (Herba-Alba) extract growth in Algeria. Int J Fundam Appl. 2018;10(1):268. https://doi.org/10.4314/jfas.v10i1.20.

    Article  CAS  Google Scholar 

  37. Waterhouse AL. Determination of total phenolics. Curr Protoc Food Anal Chem. 2002;6(1):I1-1.

    Google Scholar 

  38. Luximon-Ramma A, Bahorum T, Crosier A, Zbarsky V, Datla KK, Dexter DT, Aruom OI. Characterization of the antioxidant functions of flavonoids and proanthocyanidins in Mauritian black teas. Int Food Res. 2005;38:357–67.

    Article  CAS  Google Scholar 

  39. Jan S, Khan MR, Rashid U, Bokhari J. (2013) Assessment of antioxidant potential, total phenolics and flavonoids of different solvent fractions of monotheca buxifolia fruit. Osong Public Health Res Perspect. 2013;4(5):246–54. https://doi.org/10.1016/j.phrp.2013.09.003.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Marecek V, Mikyska A, Hampel D, Cejka P, Neuwirthova J, Malachova A, Cerkal R. ABTS and DPPH methods as a tool for studying antioxidant capacity of spring barley and malt. J Cereal Sci. 2017;73:40–5. https://doi.org/10.1016/j.jcs.2016.11.004.

    Article  CAS  Google Scholar 

  41. Luqman S, Kumar R. Correlation between scavenging properties and antioxidant activity in the extracts of Rmblica officinalis Gaertn, syn. Phyllanthus emblica L. fruit. Ann Phytomed. 2012;1(1):54–61.

    CAS  Google Scholar 

  42. Laloo D, Sahu AN. Antioxidant activities of three Indian commercially available Nagakesar: An in vitro study. J Chem Pharm Res. 2011;3(1):277–83 (www.jocpr.com).

    Google Scholar 

  43. Manel M, Kachouri F, Chouabi M, Ksontini H, Setti K, Hamdi M. Optimization of extraction parameters of protein isolate from tomato seed using response surface methodology. Food Anal Methods. 2016. https://doi.org/10.1007/s12161-016-0644-x.

    Article  Google Scholar 

  44. Feyzi S, Milani E, Golimovahhed QA. Grass Pea (Lathyrus sativus L.) protein isolate: the effect of extraction optimization and drying methods on the structure and functional properties. Food Hydrocoll. 2018;74:187–96. https://doi.org/10.1016/j.foodhyd.2017.07.031.

    Article  CAS  Google Scholar 

  45. Chakraborty SK, Singh DS, Kumbhar BK. Influence of extrusion conditions on the color of millet-legume extrudates using digital imagery. Irish J Agric Food Res. 2014;53(1):65–74. https://doi.org/10.2307/24369736.

    Article  Google Scholar 

  46. Qiao D, Hua B, Gan D, Sun Y, Ye H, Zeng X. Extraction optimized by using response surface methodology, purification and preliminary characterization of polysaccharides from Hyriopsis cumingii. Carbohydr Polym. 2009;76:422–9. https://doi.org/10.1016/j.carbpol.2008.11.004.

    Article  CAS  Google Scholar 

  47. Sahu R, Meghavarnam AK, Janakiraman S. Response surface methodology: an effective optimization strategy for enhanced production of nitrile hydratase (NHase) by Rhodococcus rhodochrous (RS-6). J Heliyon. 2020;6(10):e05111. https://doi.org/10.1016/j.heliyon.2020.e05111.

    Article  CAS  Google Scholar 

  48. Yu ZX, Zhang YY, Zhao XX, Yu L, Chen XB, Wan HT, He Y, Jin WF. Simultaneous optimization of ultrasonic-assisted extraction of Danshen for maximal tanshinone IIA and salvianolic acid B yields and antioxidant activity: a comparative study of the response surface methodology and artificial neural network. Ind Crops Prod. 2021;161:113199. https://doi.org/10.1016/j.indcrop.2020.113199.

    Article  CAS  Google Scholar 

  49. Lianfu Z, Zelong L. Optimization and comparison of ultrasound/microwave assisted extraction (UMAE) and ultrasonic assisted extraction (UAE) of lycopene from tomatoes. Ultrason Sonochem. 2008;15:731–7. https://doi.org/10.1016/j.ultsonch.2007.12.001.

    Article  CAS  PubMed  Google Scholar 

  50. Ma T, Wang Q, Wu H. Optimization of extraction conditions for improving solubility of peanut protein concentrates by response surface methodology. LWT-Food Sci Technol. 2010;43(9):1450–5.

    Article  CAS  Google Scholar 

  51. Gao LL, Li YQ, Sun GJ, Mo HZ. Optimization of protein extraction from tree peony (Paeonia suffruticosa Andr.) seed using response surface methodology. Acta Aliment. 2018;47(2):143–53. https://doi.org/10.1556/066.2017.0005.

    Article  CAS  Google Scholar 

  52. Firatligil-Durmus E, Evranuz O. Response surface methodology for protein extraction optimization of red pepper seed (Capsicum frutescens). LWT-Food Sci Technol. 2010;43(2):226–31.

    Article  CAS  Google Scholar 

  53. Zhang Y, Yu L, Jin W, Li C, Wang Y, Wan H, Yang J. Simultaneous optimization of the ultrasonic extraction method and determination of the antioxidant activities of hydroxysafflor yellow A and anhydrosafflor yellow B from safflower using a response surface methodology. Molecules. 2020;25(5):1226. https://doi.org/10.3390/molecules25051226.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Damodaran S, Parkin KL. Fennema’s food chemistry. 4th ed. Boca Raton, London: CRC Press, Taylor and Francis Group; 2008.

    Google Scholar 

  55. Zhou J, Zhang L, Li Q, Jin W, Chen W, Han J, Zhang Y. Simultaneous optimization for ultrasound-assisted extraction and antioxidant activity of flavonoids from Sophora flavescens using response surface methodology. Molecules. 2019;24:1119–27. https://doi.org/10.3390/moecules24010112.

    Article  Google Scholar 

  56. Gullon B, Gullon P, Lú-Chau TA, Moreira MT, Lema JM, Eibes G. Optimization of solvent extraction of antioxidants from Eucalyptus globulus leaves by response surface methodology: Characterization and assessment of their bioactive properties. Ind Crops Prod. 2017;108(2017):649–59. https://doi.org/10.1016/j.indcrop.07.014.

    Article  CAS  Google Scholar 

  57. Bhuyan DJ, Vuong QV, Chalmers AC, van Altena IA, Bowyer MC, Scarlett CJ. Phytochemical, antibacterial and antifungal property of an aqueous extract of Eucalyptus microcorys leaves. South African J Bot. 2017;112(2017):180–5. https://doi.org/10.1016/j.sajb.2017.05.030.

    Article  CAS  Google Scholar 

  58. Zhou J, Zheng X, Yang Q, Liang Z, Li D, Yang X, Xu J. (2013) Optimization of ultrasonic-assisted extraction and radical-scavenging capacity of phenols and flavonoids from Clerodendrum cyrtophyllum Turcz leaves. PLoS ONE. 2013;8:e68392. https://doi.org/10.1371/journal.pone.0068392.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ovando E, Rodríguez-Sifuentes L, Martínez LM, Chuck-Hernández C. Optimization of soybean protein extraction using by-products from nacl electrolysis as an application of the industrial symbiosis concept. Appl Sci. 2022;12(6):3113. https://doi.org/10.3390/app2063113.

    Article  CAS  Google Scholar 

  60. Momen S, Alavi F, Aider M. Alkali-mediated treatments for extraction and functional modification of proteins: critical and application review. Trends Food Sci Technol. 2021;2021(110):778–97.

    Article  Google Scholar 

  61. Perović MN, Knežević Jugović ZD, Antov MG. Improved recovery of protein from soy grit by enzyme-assisted alkaline extraction. J Food Eng. 2020;2020(276):109894.

    Article  Google Scholar 

  62. Koocheki A, Taherian AR, Razavi SMA, Bostan A. Response surface methodology for optimization of extraction yield, viscosity, hue and emulsion stability of mucilage extracted from Lepidium perfoliatum seeds. Food Hydrocoll. 2009;23(8):2369–79. https://doi.org/10.1016/j.foodhyd.2009.06.014.

    Article  CAS  Google Scholar 

  63. Pinto D, Vieira EF, Peixoto AF, Freire C, Freitas V, Costa P, Delerue-Matos C, Rodrigues F. Optimizing the extraction of phenolic antioxidants from chestnut shells by subcritical water extraction using response surface methodology. Food Chem. 2021;334:1275213. https://doi.org/10.1016/j.foodchem.2020.127521.

    Article  CAS  Google Scholar 

  64. Gandhi AP, Srivastava J. (2007) Studies on the production of protein isolates from defatted sesame seed (Sesamum indicum) flour and their nutritional profile. ASEAN Food J. 2007;14(3):175–80.

    Google Scholar 

  65. Hegde DM (2012) Handbook of herbs and spices. In: 23 - Sesame. Volume 2 Woodhead Publishing Series in Food Science, Technology and Nutrition, 2nd edn. Woodhead Publishing, pp 449-486. https://doi.org/10.1533/9780857095688.449

  66. Achouri A , Vincent N, Joyce IB. Sesame protein isolate: fractionation, secondary structure and functional properties. Food Res Int. 2012;42(2012):360–9. https://doi.org/10.1016/j.foodres.2012.01.001.

    Article  CAS  Google Scholar 

  67. Dravie EE, Kortei NK, Essuman EK, Tettey CO, Boakye AA, Hunkpe G. Antioxidant, phytochemical and physicochemical properties of sesame seed (Sesamum indicum L). Sci Afr. 2020;8:e00349. https://doi.org/10.1016/j.sciaf.2020.e00349.

    Article  Google Scholar 

  68. Adeyemi Jimoh W, Fagbenro OA, Adeparusi EO. Effect on processing on some minerals, anti-nutrients and nutritional composition of sesame (sesamum indicum) seeds meal. Elec J Env Agricult Food Chem. 2011;10(1):1858–64.

    Google Scholar 

  69. Djeridane A, Yousfi M, Nadjemi B, Boutassouma D, Stocker P, Vidal N. Antioxidant activity of some Algerian medicinal plants extracts containing phenolic compounds. Food Chem. 2006;97:654–60. https://doi.org/10.1016/j.foodchem.2005.04.028.

    Article  CAS  Google Scholar 

  70. Xu J, Chen S, Hu Q. Antioxidant activity of brown pigment and extracts from black sesame seed (Sesamum indicum L.). Food Chem. 2005;91(2005):79–83. https://doi.org/10.1016/j.foodchem.2004.05.051.

    Article  CAS  Google Scholar 

  71. Vishwanath HS, Anilkumar KR, Harsha SN, Khanum F, Bawa AS. In vitro antioxidant activity of Sesamum Indicum seeds. Asian J Pharm Clin Res. 2011;5(Suppl 1):56–60.

    Google Scholar 

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Roua Khalfallah wrote the main manuscript text. Manel Mechmeche helped in statistical analysis. Ines Jmoui, antioxidant activity. Hamida Ksontini reviewed the manuscript. Moktar Hamdi reviewed the manuscript. Faten Kachouri supervised the work. All authors reviewed the manuscript.

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Correspondence to Roua Khalfallah.

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Khalfallah, R., Mechmeche, M., Ksontini, H. et al. Optimization of protein extraction from sesame seeds by using response surface methodology RSM. Nutrire 49, 16 (2024). https://doi.org/10.1186/s41110-024-00259-6

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