A quercetin derivative and pectin (polymer) were modified and bonded to preserve polyphenol properties and improve absorption of the flavonol, which has a broad spectrum of therapeutic attributes.
Although considered one of the most “powerful” antioxidants in nature (found in a variety of vegetables), quercetin activity is restricted by variable absorption rates, poor water solubility and chemical stability, and low bioavailability.
The latter represents the main challenge for scientists when developing effective nutraceutical and functional foods, according to researchers.
“More effective nutraceuticals and functional foods can definitely be developed by improving the bioavailability of quercetin,” say the architects of a new functional polymer, with improved bioavailability.
There are many biopolymers already in circulation designed to increase bioavailability and resolve poor solubility of active molecules. However, pectin displays the best characteristics “for the realisation of macromolecular carriers” for oral consumption, they say.
Pectin is a linear heteropolysaccharide found in the cell walls of plant tissues and refers specifically to the compound extracted from fruit, such as apples, apricots, and pears. There is also a very high content in orange skin.
The most common, natural pectin is derived from protopectin and composed of monomeric units of D-galacturonic acid joined by glycosidic bonds to which sugars can adhere. It is safe to use, passes unchanged through gastrointestinal tract, and is eventually digested by bacterial microflora in the colon.
In the current study, an eco-friendly process was employed to develop a polymeric conjugate with “remarkable biological activities”. Macromolecular compounds were analysed to investigate antioxidant activity and toxicity against Caco-2 and HepG2 (cancer) cells, and their ability to offset the migratory properties of cells.
A hybrid molecule was synthesised by coupling quercetin and DHA and grafted with pectin to obtain a functional polymer endowed with “better antioxidant performance of parent compounds and probably improving bioavailability”.
The authors’ comment: “The opportunity to graft antioxidant structures in a biomacromolecule by an eco-friendly procedure is an innovative strategy that significantly improves the performance of the natural compounds, opening new applications in the pharmaceutical field and in the food industry.”
Two hybrid pectin-based conjugates (P2 and P3) were produced with different amounts of quercetin (P2 contained more) and enhanced with ascorbic acid (redox couple). The purified solution was frozen and dried to produce a vaporous solid. A ‘blank pectin’ (PB) preparation without antioxidant molecules was used as a control.
Total phenolic content, total antioxidant activity and scavenger activity against hydrophilic (ABTS) and lipophilic (DPPH) radical species were investigated.
The modified pectin (P2 and P3) significantly reduced phenolic content (29.6%) and total antioxidant capacity (33%), with loss of antioxidant performance attributed to DHA and subsequent disappearance of one reactive site.
“At the same time, the spatial conformation of the hydrocarbon chain can hinder the interaction between the other hydroxylic groups and the radical species,” the authors explain.
P2 displayed the greatest anti-radical activity to reach the half maximal inhibitory concentration (IC50), while P3 only inhibited 44.1%. Polyphenolic content was significantly higher in P2, compared to P3, and the higher dose also recorded a more than 30% increase in total antioxidant capacity.
In relation to hydrophilic activity (against ABTS radicals), neither polymer performed well. P2 reached an IC30 value, while P3 demonstrated 50% lower efficacy.
Results indicated a dose-dependent reduction in viability of tumour cells and reduced migration with quercetin, while there was no affect with the PB.
The authors suggest that data demonstrated the formula provides a useful alternative to improve bioavailability of quercetin-derivatives through covalent binding to the pectin chain.
Furthermore, it offers “a very versatile and effective means to transport polyphenol compounds, both in terms of protection of the polyphenol itself and in terms of biological activity manifested in the matrices in which it will be used,” they say.
Published online, October 11, 2022: http://doi.org/10.3390/nutraceuticals2040021
‘Development of Quercetin-DHA Ester-Based Pectin Conjugates as New Functional Supplement: Effects on Cell Viability and Migration’
Authors: Gabriele Carullo, Umile Gianfranco Spizzirri, Rocco Malivindi, Vittoria Rago, Marisa Francesca Motta, Danilo Lofaro, Donatella Restuccia and Francesca Aiello