Simultaneous optimization of ultrasound-assisted extraction of antioxidants and tyrosinase inhibitory activities of Semen Oroxyli flavonoids using response surface methodology

  • Xing-shuo Yin
  • Xue-qin Zhang
  • De-qiang LiEmail author
Original Paper


In this study, the ultrasound-assisted extraction (UAE) of flavonoids with maximal antioxidant and tyrosinase inhibitory activities and identification of the principal individual flavonoids compounds of Semen Oroxyli by UHPLC-DAD-QTOF-MS/MS was proposed. The method was optimized by a three-factor-three-level Box–Behnken design (BBD) and Derringer’s desirability function using methanol concentration, extraction time, and liquid/solid ratio as factors, while, the total flavonoids content (TFC), antioxidant activities (DPPH, ABTS, FRAP, superoxide anion and hydroxyl radicals) and tyrosinase inhibitory activity as responses. The experimental results showed that the optimal extraction conditions were as followed: a solvent of 69.90% methanol, an extraction time of 30.64 min and a liquid/solid ratio of 31.30 mL/g, which give individual response values of 19.79 mg RE/g, 78.66%, 99.92%, 19.05 mM FE/g, 20.49%, and 13.37% for TFC, DPPH, ABTS, FRAP, superoxide anion and hydroxyl radicals, respectively. In addition, the tyrosinase inhibition assay showed that the extract of Semen Oroxyli exhibited strong inhibitory activity against the tyrosinase. There were no significant differences between the results of the optimization experiments and those predicted by the models. By UHPLC-DAD-QTOF-MS/MS analysis, the main flavonoids identified in the optimized UAE extracts of Semen Oroxyli were oroxin B, oroxin A, chrysin-7-O-β- d-glucuronid, baicalein and chrysin.


Semen oroxyli Ultrasound-assisted extraction (UAE) Antioxidant activity Tyrosinase inhibition Response surface methodology (RSM) UHPLC-DAD-QTOF-MS/MS 



This work was supported by the National Natural Science Foundation of China (81603066), Talent Training Project of Hebei Province (A201902012) and the Scientific Research Funds of the Second Hospital of Hebei Medical University (2h2019031).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


  1. 1.
    M.M. Joe, A. Benson, M. Ayyanar, T. Sa, Bioactive Compounds and Medical Significance of Some Endangered Medicinal Plants from the Western Ghats Region of India Biotechnology of Bioactive Compounds: Sources and Applications (Wiley, Hoboken, 163, 2015)Google Scholar
  2. 2.
    National Commission of Chinese Pharmacopoeia, Pharmacopoeia of People’s Pepublic of China (China Medical Sciences Press, Beijing, 2010), p. 60Google Scholar
  3. 3.
    L.J. Chen, H. Song, X.Q. Lan, D.E. Games, I.A. Sutherland, J. Chromatogr. A. 1063, 241 (2005)PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    P. Sithisarn, P. Nantateerapong, P. Rojsanga, P. Sithisarn, Molecules 21, 446 (2016)PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    K. Lalrinzuali, M. Vabeiryureilai, G.C. Jagetia, Int. J. Inflamm. 2016, 1 (2016)CrossRefGoogle Scholar
  6. 6.
    D.Q. Li, J. Zhao, S.P. Li, J. Chromatogr. A. 1345, 50 (2014)PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    J. SatyaEswari, S. Dhagat, S. Naik, S. Dibya, Pharm. Bioprocess. 6, 7 (2018)Google Scholar
  8. 8.
    N.N. Li, X.S. Meng, Y.R. Bao, S. Wang, T.J. Li, Pharmacogn. Mag. 14, 207 (2018)PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    D. Gentile, M. Fornai, C. Pellegrini, R. Colucci, C. Blandizzi, L. Antonioli, Nutr. Res. Rev. 31, 239 (2018)PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    V. D’Amelia, R. Aversano, P. Chiaiese, D. Carputo, Phytochem. Rev. 17, 611 (2018)CrossRefGoogle Scholar
  11. 11.
    A. Bose, G.A. Petsko, D. Eliezer, J. Parkinson's Dis. 8, 385 (2018)CrossRefGoogle Scholar
  12. 12.
    M. Fan, H. Ding, G. Zhang, X. Hu, D. Gong, LWT-Food Sci. Technol. 107, 25 (2019)CrossRefGoogle Scholar
  13. 13.
    A. Maack, A. Pegard, Fitoterapia 111, 95 (2016)PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    T. Belwal, S.M. Ezzat, L. Rastrelli, I.D. Bhatt, M. Daglia, A. Baldi, H.P. Devkota, I.E. Orhan, J.K. Patra, G. Das, C. Anandharamakrishnan, L. Gomez-Gomez, S.F. Nabavi, S. Mohammad, TrAC Trends Anal. Chem. 100, 82 (2018)CrossRefGoogle Scholar
  15. 15.
    A. Ali, X.Y. Lim, C.H. Chong, S.H. Mah, B.L. Chua, LWT-Food Sci. Technol. 89, 681 (2018)CrossRefGoogle Scholar
  16. 16.
    J. Zhou, L.C. Zhang, Q.P. Li, W.F. Jin, W.Y. Chen, J. Han, Y.Y. Zhang, Molecules 24, 112 (2019)CrossRefGoogle Scholar
  17. 17.
    Y. Zhang, Y. Zhang, A.A. Taha, Y. Ying, X. Li, X. Chen, C. Ma, Ind. Crops Prod. 117, 118 (2018)CrossRefGoogle Scholar
  18. 18.
    T. Belwal, I.D. Bhatt, R.S. Rawal, V. Pande, Ind. Crops Prod. 95, 393 (2017)CrossRefGoogle Scholar
  19. 19.
    B.C. Liau, V.K. Ponnusamy, M.R. Lee, T.T. Jong, J.H. Chen, Ind. Crops Prod. 95, 296 (2017)CrossRefGoogle Scholar
  20. 20.
    Y. Zhou, X.Y. Xu, R.Y. Gan, J. Zheng, Y. Li, J.J. Zhang, D.P. Xu, H.B. Li, Antioxidants 8, 200 (2019)PubMedCentralCrossRefGoogle Scholar
  21. 21.
    N. Bouaoudia-Madi, L. Boulekbache-Makhlouf, K. Madani, A. Silva, S. Dairi, S. Oukhmanou-Bensidhoum, S.M. Cardoso, Antioxidants 8, 205 (2019)PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    F. Chemat, M.K. Khan, Ultrason. Sonochem. 18, 813 (2011)PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    A. Pandey, T. Belwal, K.C. Sekar, I.D. Bhatt, R.S. Rawal, Ind. Crops Prod. 119, 218 (2018)CrossRefGoogle Scholar
  24. 24.
    N. Nabet, B. Gilbert-López, K. Madani, M. Herrero, E. Ibáñez, J.A. Mendiola, Ind. Crops Prod. 129, 395 (2019)CrossRefGoogle Scholar
  25. 25.
    R.H. Myers, D.C. Montgomery, C.M. Anderson-Cook, Response Surface Methodology: Process and Product Optimization Using Designed Experiments (Wiley, Hoboken, 2016)Google Scholar
  26. 26.
    F.J. Leyva-Jiménez, J. Lozano-Sánchez, L. Borrás-Linares, D. Arráez-Román, A. Segura-Carretero, Food. Res. Int. 109, 213 (2018)PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    W. Setyaningsih, I.E. Saputro, C.A. Carrera, M. Palma, C.G. Barroso, Food Chem. 225, 1 (2017)PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    X.J. Zhao, J.G. Liu, Y.L. Hu, Y.P. Fan, D.Y. Wang, J. Yuan, L. Xu, L. Cui, Z. Jing, Int. J. Biol. Macromol. 51, 299 (2012)PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    A.U. Arvindekar, K.S. Laddha, Ind. Crops Prod. 83, 587 (2016)CrossRefGoogle Scholar
  30. 30.
    C.Y. Dai, P.F. Liu, P.R. Liao, Y. Qu, C.X. Wang, Y. Yang, X.M. Cui, Molecules 23, 2219 (2018)PubMedCentralCrossRefGoogle Scholar
  31. 31.
    X. Zhai, C. Zhu, Y. Li, Y. Zhang, Z. Duan, X.B. Yang, Int. J. Biol. Macromol. 109, 244 (2018)PubMedCrossRefGoogle Scholar
  32. 32.
    C. Puangbanlang, K. Sirivibulkovit, D. Nacapricha, Y. Sameenoi, Talanta 198, 542 (2019)PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Y. Wang, Y. Gao, H. Ding, S. Liu, X. Han, J. Gui, D. Liu, Food Chem. 218, 152 (2017)PubMedCrossRefGoogle Scholar
  34. 34.
    C.M. Yin, X.Z. Fan, Z. Fan, D.F. Shi, H. Gao, Int. J. Biol. Macromol. 111, 446 (2018)PubMedCrossRefGoogle Scholar
  35. 35.
    Z. Yang, Y. Zhang, L. Sun, Y. Wang, X. Gao, Y. Cheng, Anal. Chim. Acta. 719, 87 (2012)PubMedCrossRefGoogle Scholar
  36. 36.
    J.H. Xie, C.J. Dong, S.P. Nie, F. Li, Z.J. Wang, M.Y. Shen, M.Y. Xie, Food Chem. 186, 97 (2015)PubMedCrossRefGoogle Scholar
  37. 37.
    L. Yang, Y.L. Gao, J.G. Jiang, Q.S. Lin, J. Chen, L. Zhu, J. Sep. Sci. 33, 1349 (2010)PubMedGoogle Scholar
  38. 38.
    D.L. Hu, M.J. Wu, Lishizhen Med. Mat Med. Res. 21, 2475 (2010)Google Scholar
  39. 39.
    K. Liu, Y. Lan, N. Yang, Z. Chen, W. Zhang, Northwest Pharm. J. 30, 669 (2015)Google Scholar
  40. 40.
    Y.G. Li, Study on extraction-isolation and pharmacological activities of total flavonoids from Oroxylun indicum (L) vent (D), University of South China, 2014, pp. 8–10Google Scholar
  41. 41.
    Q.X. Guan, S.L. Sun, G.Y. Zhang, S.Y. Zhang, C. Sun, M. Wang, C.C. Han, X. Liu, Spec. Wild Econ. Anim. Plant. Res. 2, 20 (2016)Google Scholar
  42. 42.
    Y. Wu, W.J. Bai, X. Wei, Chin. J. Exper Trad Med Formul. 24, 99 (2018)Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PharmacyThe Second Hospital of Hebei Medical UniversityShijiazhuangPeople’s Republic of China

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