Isolation, solubilization and biological activity of isoflavonoids from Fabaceae family

doctoral thesis

• Title (croatian): Izolacija, solubilizacija i biološka aktivnost izoflavona iz porodice Fabaceae
• Author: Barbara Fumić
• Mentor: Marijana Zovko Končić (mentor)
• Mentor: Mario Jug (komentor)
• Committee member: Sanda Vladimir-Knežević (predsjednik povjerenstva)
• Committee member: Željka Vanić (član povjerenstva)
• Committee member: Mila Lovrić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacognosy); Zagreb
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2020-06-04, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Mucopolysaccharidoses are hereditary metabolic diseases characterized by the accumulation of various glycosaminoglycans in the tissues of the diseased. Isoflavones are secondary plant metabolites that can slow down the synthesis of glycosaminoglycans, but their therapeutic potential is significantly limited by their poor oral bioavailability. In this thesis, the ethanol and cyclodextrin ultrasound-assisted extraction of aerial parts of two plant species from the family Fabaceae, Medicago sativa and Lotus corniculatus, was compared. The study was conducted using response surface methodology based on a Box-Benkhen design with three independent variables. The influence of isoflavones, the prepared extracts and inclusion complexes of selected isoflavones with different cyclodextrins on oxidative stress and glycosaminoglycan synthesis in fibroblast cell lines of patients with mucopolysaccharidosis was evaluated. Although ethanol was a more suitable solvent for the extraction of total polyphenols from M. sativa, the use of hydroxypropyl--cyclodextrin allowed for a more selective extraction of total flavonoids whose amount was as much as three times higher than in ethanol extracts. The amount of total flavonoids extracted using cyclodextrin from L. corniculatus was two times greater than the amount of total flavonoids of the species M. sativa. The cyclodextrin complexes of these extracts showed, depending on the dose, a significant decrease in glycosaminoglycan levels in fibroblast cells of patients with mucopolysaccharidoses, with no significant cytotoxic effect.

Abstract (croatian)

Mukopolisaharidoze su nasljedne metaboličke bolesti koje karakterizira nakupljanje različitih glikozaminoglikana u tkivima oboljelih. Izoflavoni su sekundarni biljni metaboliti koji mogu usporiti sintezu glikozaminoglikana, ali je njihov terapijski potencijal značajno ograničen slabom oralnom bioraspoloživošću. U radu su uspoređene etanolna i ciklodekstrinska ultrazvučna ekstrakcija zeleni dvije biljne vrste iz porodice Fabaceae, Medicago sativa i Lotus corniculatus. Istraživanje je provedeno korištenjem metodologije površine odgovora temeljene na Box-Benkhen dizajnu s tri nezavisne varijable. Uspoređen je utjecaj izoflavona, priređenih ekstrakata te inkluzijskih kompleksa odabranih izoflavona s različitim ciklodekstrinima na oksidativni stres i sintezu glikozaminoglikana u staničnim linijama fibroblasta bolesnika oboljelih od mukopolisaharidoza. Iako je etanol bio prikladnije otapalo za ekstrakciju ukupnih polifenola iz M. sativa, uporaba hidroksipropil--ciklodekstrina omogućila je selektivniju ekstrakciju ukupnih flavonoida čija je količina bila čak tri puta veća nego u etanolnim ekstraktima. Količina ukupnih flavonoida ekstrahirana korištenjem ciklodekstrina iz biljnog materijala vrste L. corniculatus bila je još dva puta veća od količine ukupnih flavonoida iz vrste M. sativa. Ciklodekstrinski kompleksi navedenih ekstrakata pokazali su, ovisno o dozi, značajno sniženje razine glikozaminoglikana u stanicama fibroblasta bolesnika oboljelih od mukopolisaharidoza, bez značajnog citotoksičnog učinka.

• Keywords: cyclodextrines; isoflavones; Lotus corniculatus; Medicago sativa; mucopolysaccharidoses
• Keywords (croatian): ciklodekstrini; izoflavoni; Lotus corniculatus; Medicago sativa; mukopolisaharidoze
• Language: english
• URN:NBN: urn:nbn:hr:163:338856
• Promotion: 2021
• Study programme: Title: Pharmacy and biochemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor znanosti (doktor znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-05-18 14:58:37