Development of cyclodextrin-based extract of Lotus corniculatus as a potential substrate reduction therapy in mucopolysaccharidoses type III

  • Barbara Fumić
  • Marijana Zovko Končić
  • Mario Jug
Original Article


A novel sustainable and eco-friendly procedure simultaneously combining the use of ultrasound irradiation and hydroxypropyl-β-cyclodextrin (HPβCD) complexation was used to extract phytochemicals from Lotus corniculatus and to prepare flavonoid rich extract having potential as substrate reduction therapy of mucopolysaccharidosis type III (MPS III), a rare autosomal recessive lysosomal storage disorder. For that instance, Box-Behnken design and response surface methodology was employed to statistically assess the influence of HPβCD concentration, ultrasonic power, and extraction time on the total phenolic compounds, total flavonoids, total phenolic acids and radical scavenging activity (RSA) of the extracts prepared, chosen as the responses indicative of the product quality and performance. The potential of such optimised extract to modulate accumulation of gylcosoaminoglycans (GAGs) was evaluated on the fibroblast obtained from patients suffering from MPS type III. Optimized extract prepared by 45 min extraction using HPβCD at concentration of 20 mM and ultrasonic irradiation of 648 W was rich in flavonoids (1.36 mg/mL) and showed notable RSA of 1.04 mg/mL. Freeze-dried extract, at concentration of 3 and 6 µg/mL, reduced GAG levels in skin fibroblasts by 33.97 and 50.08%, respectively, without any toxic effects at given doses, showing a potential to be considered as a part of the substrate reduction therapy of MPS III.


Lotus corniculatus Hydroxypropyl-β-cyclodextrin Polyphenols Flavonoids Radical scavenging activity Glycosoaminoglycans 



Authors are thankful to Vedran Šegota, an expert associate of Herbarium Croaticum at Division of Botany, Department of Biology, Faculty of Science, University of Zagreb for the help in identification of the plant material. The financial support of University of Zagreb in the frame of the project Isolation and modulation of antioxidative properties of plant polyphenols by the use of cyclodextrins (Grant No. BM1.10) is kindly acknowledged.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The research was performed in accordance with ethical committee approval (Class: 643-03/l4-QL/04; No. 251-62-03-L4-33; Zagreb, 16 May 2014).


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© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.XelliaZagrebCroatia
  2. 2.Department of Pharmacognosy, Faculty of Pharmacy and BiochemistryUniversity of ZagrebZagrebCroatia
  3. 3.Department of Pharmaceutical Technology, Faculty of Pharmacy and BiochemistryUniversity of ZagrebZagrebCroatia

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