A High-Yield Process for Extraction of Hesperidin from Orange (Citrus sinensis L. osbeck) Peels Waste, and Its Transformation to Diosmetin, A Valuable and Bioactive Flavonoid


An alternative and high-yield method to obtain hesperidin, a bitter flavored flavanone glucoside, from orange (Citrus sinensis L. osbeck) peels waste is described. The proposed process, which add high-value to this kind of residue from orange juice processing industry, was based on a successful modification applied to extraction of naringin from grapefruit. This method involves extraction with methanol and crystallization in water with addition of dichloromethane, requiring shorter times and reducing of volume of solvent employed. Changing to hot extraction with methanol of fresh orange albedo led to higher yields of extraction in half the time required due to the direct method, avoiding air-dried albedo step. Application of described method led to 2.8% yield (w/w dry albedo) of hesperidin extracted in 89.4% purity determined by HPLC analysis. To add high-value to the flavanone obtained, it was subject to chemical transformation (oxidation and hydrolysis, 83% and 88% yield, respectively) into the flavone diosmetin (73% yield for 2 steps), an expensive and naturally-occurring flavonoid in low yields which exhibits a wide range of pharmacological properties.

Graphic Abstract

This paper describes high-yield process for extraction of hesperidin from orange peels waste, and their use as feedstock in the production of diosmetin.

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  1. 1.

    US Department of Agriculture, Citrus: World Markets and Trade, Report July 2019.

  2. 2.

    Satari, B., Karimi, K.: Citrus processing wastes: environmental impacts, recent advances, and future perspectives in total valorization. Resour. Conserv. Recycl. 129, 153–167 (2018). https://doi.org/10.1016/j.resconrec.2017.10.032

    Article  Google Scholar 

  3. 3.

    Sharma, K., Mahato, N., Cho, M.H.: Converting citrus wastes into value-added products: economic and environmently friendly approaches. Nutrition 34, 29–46 (2017). https://doi.org/10.1016/j.nut.2016.09.006

    Article  Google Scholar 

  4. 4.

    Sharma, K., Mahato, N., Lee, Y.R.: Extraction, characterization and biological activity of citrus flavonoids. Rev. Chem. Eng. (2018). https://doi.org/10.1515/revce-2017-0027

    Article  Google Scholar 

  5. 5.

    Zema, D.A., Calabrò, P.S., Folino, A., Tamburino, V., Zappia, G., Zimbone, S.M.: Valorization of citrus processing waste: a review. Waste Manag. 80, 252–273 (2018). https://doi.org/10.1016/j.wasman.2018.09.024

    Article  Google Scholar 

  6. 6.

    Putnik, P., Kovacevic, D.B., Jambrak, A.R., Barba, F.J., Cravotto, G., Binello, A., Lorenzo, J.M., Shpigelman, A.: Innovative “green” and novel strategies for the extraction of bioactive added value compounds from citruswastes—a review. Molecules 22, 680–704 (2017). https://doi.org/10.3390/molecules22050680

    Article  Google Scholar 

  7. 7.

    Hargreaves, J.C., Adl, M.S., Warman, P.R.: A review of the use of composted municipal solid waste in agriculture. Agric. Ecosyst. Environ. 123, 1–14 (2008). https://doi.org/10.1016/j.agee.2007.07.004

    Article  Google Scholar 

  8. 8.

    Galati, E.M., Monforte, M.T., Kirjavainen, S., Forestieri, A.M., Trovato, A., Tripodo, M.M.: Biological effects of hesperidin, a citrus flavonoid. (Note I): antiinflammatory and analgesic activity. Farmaco 40, 709–712 (1994)

    Google Scholar 

  9. 9.

    Bok, S.H., Lee, S.H., Park, Y.B., Bae, K.H., Son, K.H., Jeong, T.S., Choi, M.S.: Plasma and hepatic cholesterol and hepatic activities of 3-hydroxy-3-methyl-glutaryl-CoA reductase and acyl CoA: cholesterol transferase are lower in rats fed citrus peel extract or a mixture of citrus bioflavonoids. J. Nutr. 129, 1182–1185 (1999). https://doi.org/10.1093/jn/129.6.1182

    Article  Google Scholar 

  10. 10.

    Galati, E.M., Kirjavainen, S., Forestieri, A.M., Rossitto, A., Monforte, M.T.: Biological effects of hesperidin, a Citrus flavonoid. (Note III): antihypertensive and diuretic activity in rat. Farmaco 51, 219–221 (1996)

    Google Scholar 

  11. 11.

    Raza, S.S., Khan, M.M., Ahmad, A., Ashafaq, M., Khuwaja, G., Tabassum, R., Javed, H., Siddiqui, M.S., Safhi, M.M., Islam, F.: Hesperidin ameliorates functional and histological outcome and reduces neuroinflammation in experimental stroke. Brain Res. 1420, 93–105 (2011). https://doi.org/10.1016/j.brainres.2011.08.047

    Article  Google Scholar 

  12. 12.

    Chen, M.C., Ye, Y.Y., Guang, J.I., Jian-Wen, L.I.U.: Hesperidin upregulates heme oxygenase-1 to attenuate hydrogen peroxide-induced cell damage in hepatic L02 cells. J. Agric. Food Chem. 58, 3330–3335 (2010). https://doi.org/10.1021/jf904549s

    Article  Google Scholar 

  13. 13.

    Beltagy, A.M.: Microwave—assisted extraction of flavonoids and profiling flavonoid cytotoxicity against Hep-G2 human cancer cell line. Int. J. Pharm. Sci. Res. 8, 4573–4581 (2017). https://doi.org/10.13040/IJPSR.0975-8232.8(11).4573-81

    Article  Google Scholar 

  14. 14.

    Androutsopoulos, V.P., Spandidos, D.A.: The flavonoids diosmetin and luteolin exert synergistic cytostatic effects in human hepatoma HepG2 cells via CYP1A-catalyzed metabolism, activation of JNK and ERK and P53/P21 up-regulation. J. Nutr. Biochem. 24, 496–504 (2013). https://doi.org/10.1016/j.jnutbio.2012.01.012

    Article  Google Scholar 

  15. 15.

    Crespo, M.E., Gálvez, J., Cruz, T., Ocete, M.A., Zarzuelo, A.: Anti-inflammatory activity of diosmin and hesperidin in rat colitis induced by TNBS. Planta Med. 65, 651–653 (1999). https://doi.org/10.1055/s-2006-960838

    Article  Google Scholar 

  16. 16.

    Benavente-García, O., Castillo, J.: Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity. J. Agric. Food Chem. 56, 6185–6205 (2008)

    Article  Google Scholar 

  17. 17.

    Silva, L.C.R.C., David, J.M., Borges, R.S.Q., Ferreira, S.L.C., David, J.P., Reis, P.S., Bruns, R.E.: Determination of flavanones in orange juices obtained from different sources by HPLC/DAD. J. Anal. Methods Chem. 2014, 1–5 (2014). https://doi.org/10.1155/2014/296838

    Article  Google Scholar 

  18. 18.

    Kawaii, S., Tomoro, Y., Katase, E., Ogawa, K., Yano, M.: Quantitation of flavonoid constituents in citrus fruits. J. Agric. Food Chem. 47, 3565–3571 (1999). https://doi.org/10.1021/jf990153+

    Article  Google Scholar 

  19. 19.

    Sawalha, S.M.S., Arráez-Román, D., Segura-Carretero, A., Fernández-Gutiérrez, A.: Quantification of main phenolic compounds in sweet and bitter orange peel using CE-MS/MS. Food Chem. 116, 567–574 (2009). https://doi.org/10.1016/j.foodchem.2009.03.003

    Article  Google Scholar 

  20. 20.

    Lachos-Perez, D., Baseggio, A.M., Mayanga-Torres, P.C., Junior, M.R.M., Rostagno, M.A., Martínez, J., Forster-Carneiro, T.: Subcritical water extraction of flavanones from defatted orange peel. J. Supercrit. Fluids 138, 7–16 (2018). https://doi.org/10.1016/j.supflu.2018.03.015

    Article  Google Scholar 

  21. 21.

    Cypriano, D.Z., da Silva, L.L., Tasic, L.: High value-added products from the orange juice industry waste. Waste Manag. 79, 71–78 (2018). https://doi.org/10.1016/j.wasman.2018.07.028

    Article  Google Scholar 

  22. 22.

    Lahmer, N., Belboukhari, N., Cheriti, A., Sekkoum, K.: Hesperidin and hesperitin preparation and purification from Citrus sinensis peels. Der Pharm. Chem. 7, 1–4 (2015)

    Google Scholar 

  23. 23.

    Sudto, K., Pornpakakul, S., Wanichwecharungruang, S.: An efficient method for the large scale isolation of naringin from pomelo (Citrus grandis) peel. Int. J. Food Sci. Technol. 44, 1737–1742 (2009). https://doi.org/10.1111/j.1365-2621.2009.01989.x

    Article  Google Scholar 

  24. 24.

    Victor, M.M., David, J.M., Sakukuma, M.C.K., França, E.L., Nunes, A.V.J.: A simple and efficient process for the extraction of naringin from grapefruit peel waste. Green Process. Synth. 7, 524–529 (2018). https://doi.org/10.1515/gps-2017-0112

    Article  Google Scholar 

  25. 25.

    Correia-da-Silva, M., Souza, E., Duarte, B., Marques, F., Carvalho, F., Cunha-Ribeiro, L.M., Pinto, M.M.M.: Flavonoids with an oligopolysulfated moiety: a new class of anticoagulant agents. J. Med. Chem. 54, 95–106 (2011). https://doi.org/10.1021/jm1013117

    Article  Google Scholar 

  26. 26.

    Bampidis, V.A., Robinson, P.H.: Citrus by-products as ruminant feeds: a review. Anim. Feed Sci. Technol. 128, 175–217 (2006). https://doi.org/10.1016/j.anifeedsci.2005.12.002

    Article  Google Scholar 

  27. 27.

    Mahato, N., Sharma, K., Sinha, M., Cho, M.H.: Citrus waste derived nutra-/pharmaceuticals for health benefits: current trends and future perspectives. J. Funct. Foods 40, 307–316 (2018). https://doi.org/10.1016/j.jff.2017.11.015

    Article  Google Scholar 

  28. 28.

    Zhang, W., Yi, D., Gao, K., Liu, M., Yang, J., Liao, X., Yang, B.: Hydrolysis of scutellarin and related glycosides to scutellarein and the corresponding aglycones. J. Chem. Res. 38, 396–398 (2014). https://doi.org/10.3184/174751914X14017253941699

    Article  Google Scholar 

  29. 29.

    Duan, K., Liu, H., Fan, H., Zhang, J., Wang, Q.: Synthesis and anticholinesterase inhibitory activity of Mannich base derivatives of flavonoids. J. Chem. Res. 38, 443–446 (2014). https://doi.org/10.3184/174751914X14031988231263

    Article  Google Scholar 

  30. 30.

    Li, Y., Cai, S., He, K., Wang, Q.: Semisynthesis of polymethoxyflavonoids from naringin and hesperidin. J. Chem. Res. 38, 287–290 (2014). https://doi.org/10.3184/174751914X13966139490181

    Article  Google Scholar 

  31. 31.

    Cai, S., Wu, Z., Wu, J., Wang, Q., Shan, Y.: Synthesis and biological activities of natural flavonoid diosmetin and its derivatives. Chin. J. Org. Chem. 32, 560–566 (2012). https://doi.org/10.6023/cjoc1109081

    Article  Google Scholar 

  32. 32.

    Shan, Y., Li, Q.-Y., Wang, Q.-A., Li, Z.-H.: Semisynthesis of five bioactive flavonoids from hesperidin. Chin. J. Org. Chem. 28, 1024–1028 (2008)

    Google Scholar 

  33. 33.

    Oyama, K., Kondo, T.: Total synthesis of apigenin 7,4′-di-O-β-glucopyranoside, a component of blue flower pigment of Salvia patens, and seven chiral analogues. Tetrahedron 60, 2025–2034 (2004). https://doi.org/10.1016/j.tet.2004.01.001

    Article  Google Scholar 

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The authors are grateful to Brazilian Agencies CNPq (National Council for Scientific and Technological Development), CAPES (Coordination for the Improvement of Higher Education Personnel) and INCT E&A (National Institute for Science and Technology for Energy and Environment) for financial support. The authors thanks Laboratory of High Resolution Nuclear Magnetic Resonance (LAREMAR) of the Department of Chemistry (UFMG, Brazil) for conducting NMR spectra.

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Victor, M.M., David, J.M., Cortez, M.V.M. et al. A High-Yield Process for Extraction of Hesperidin from Orange (Citrus sinensis L. osbeck) Peels Waste, and Its Transformation to Diosmetin, A Valuable and Bioactive Flavonoid. Waste Biomass Valor 12, 313–320 (2021). https://doi.org/10.1007/s12649-020-00982-x

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  • Orange waste
  • Hesperidin extraction
  • Flavonoid
  • Diosmetin
  • High-value by-product