engleski

Therapeutic potential of hydroxypropyl-β-cyclodextrin based extract of Medicago sativa in the treatment of mucopolysaccharidoses

Mucopolysaccharidoses (MPS) are inherited metabolic disorders resulting in dysfunction of enzymes involved in degradation of glycosaminoglycans (GAGs), leading to severe clinical symptoms and significantly shortened life span of patients. Flavonoids were recognized as GAG-metabolism modulators, able to correct GAG cell storage. Therefore, the aim of this work was development of efficient and eco-friendly extraction process of phytochemicals from Medicago sativa by simultaneous use of ultrasound extraction and hydroxypropyl-ß-cyclodextrin (HPßCD) complexation and investigation of the potential of such extract as GAG metabolism modulator. Box–Behnken design and response surface methodology were used in order to optimize the extraction process, considering HPßCD concentration, ultrasonic power, and extraction time as key parameters. The dependent variables included total phenolic (TP) and total flavonoid content (TF), DPPH radical scavenging activity (RSA) and Fe2+ chelating activity (ChA), due to importance of oxidative stress in MPS pathology. The developed technology using HPßCD leads to more selective flavonoid extraction from M. sativa, than obtained either by the use of water or ethanol. The lyophilization of extracts resulted in products with high RSA, suitable for further use. The application of 20 mM HPßCD solution, 432 W ultrasonic power and extraction time of 45 min resulted in extract with both the highest TF and the lowest RSA IC50. This extract reduced GAG levels in skin fibroblasts of MPS III patient in dose dependent manner. At concentration of 3 and 6 ug/mL, the observed GAG levels were reduced by 41.2 and 51.1 %, respectively, clearly demonstrating the validity of selected approach.

Medicago sativa ; Fabaceae ; hydroxypropyl-β-cyclodextrin ; polyphenols ; radical scavenging activity ; chelating activity ; glycosaminoglycans

nije evidentirano