Flavonoid-enriched fractions from Parastrephia lucida: Phytochemical, anti-inflammatory, antioxidant characterizations, and analysis of their toxicity

Abstract

Parastrephia lucida (Meyen) Cabrera is an endemic species from the Argentinean Puna used in traditional medicine to relieve inflammation. To give scientific support to the ethnopharmacological claim, a bio-guided fractionation of a P. lucida extract was carried out according to its antioxidant activity (in vitro by different primary and secondary methodologies and in vivo on Caenorhabditis elegans) and its ability to inhibit pro-inflammatory enzymes (hyaluronidase and xanthine oxidase). Acute toxicity and genotoxicity of P. lucida were also studied by using Artemia salina and C. elegans bioassays, and Ames test, respectively. Compound characterization of P. lucida extracts and fractions was performed through UHPLC-quadrupole Orbitrap mass spectrometry. P. lucida total methanolic (MeOH) and dichloromethane (DCM) extracts (obtained from the partition of MeOH), showed high flavonoid contents (25.6 and 28.0 µg QE/mg DW) and significant inhibition of pro-inflammatory enzymes (IC50: 320.0 and 280.0 µg/mL on hyaluronidase, and IC50: 53.0 and 44.0 µg/mL on xanthine oxidase, respectively), as well as in vitro and in vivo antioxidant capacity. From DCM, fractions E and F, showed a lack of toxicity or genotoxic, inhibited the xanthine oxidase activity 4-fold than DCM extract, and exhibited high in vivo antioxidant activity, evidenced by the protection of C. elegans against oxidative damage caused by H2O2 and Paraquat between 20 and 30 %. Besides, fractions E and F extended the nematode lifespan between 19 and 38%. Sixty-three metabolites, including several phenolic acids, coumarins, methoxylated flavonoids, tremetone derivates, and clerodane diterpenes, were accurately identified in the DCM fractions of P. lucida. This work not only scientifically supports P. lucida traditional use but also contributes to the search for new natural compounds aimed to treat processes related to inflammatory diseases, associated with oxidative stress.