Glycosylation of chrysin with β-d-glucose tetraacetate (LQFM280) enhances its in vitro and in vivo neuroprotective effects against the toxicity induced by 3-nitropropionic acid.

Autor: Pereira RM; Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Campos HM; Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., de Oliveira Ferreira PY; Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Uchenna N; Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Silva YS; Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Okoh VI; Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Pruccoli L; Department for Life Quality Studies, Alma Mater Studiorum - University of Bologna, Rimini, Italy., Arruda EL; Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil., Lião LM; Institute of Chemistry, Federal University of Goiás, Goiânia, GO, Brazil., Mota PAA; Institute of Mathematics and Statistics, Federal University of Goiás, Goiânia, GO, Brazil., Leite JA; Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., de Castro Georg R; Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., da Matta DH; Institute of Mathematics and Statistics, Federal University of Goiás, Goiânia, GO, Brazil., Dos Santos FCA; Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Costa EA; Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Tarozzi A; Department for Life Quality Studies, Alma Mater Studiorum - University of Bologna, Rimini, Italy., Menegatti R; Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil., Ghedini PC; Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil. pcghedini@ufg.br.; Biochemical and Molecular Pharmacology Laboratory, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Cep 74690-900, Brazil. pcghedini@ufg.br.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Oct 16. Date of Electronic Publication: 2024 Oct 16.
DOI: 10.1007/s00210-024-03526-5
Abstrakt: Chrysin (CHR) is a naturally occurring flavonoid found in the human diet, recognized for its potential in preventing neurodegenerative diseases. However, its limited water solubility restricts its bioavailability and therapeutic applications. To address this issue and bolster the neuroprotective properties of CHR for potential nutraceutical or medicinal use, we investigated a novel compound, LQFM280, formed by conjugating CHR with β-d-glucose tetraacetate. We conducted both in vitro (using SH-SY5Y cells, mutant STHdhQ111/Q111 cells, and wild-type STHdhQ7/Q7 cells), and in vivo (mice) neurotoxicity experimental model induced by 3-nitropropionic acid, which mimic biological changes akin to Huntington's disease in humans. Compared to non-glycosylated CHR, LQFM280 showed superior in vitro effects in preventing neurotoxicity caused by increased mitochondrial vulnerability due to mutant huntingtin. In vivo findings demonstrated that LQFM280 has heightened efficacy in mitigating weight loss, memory and locomotor impairment, oxidative stress, and disruptions in the antioxidant defense system, as well as succinate dehydrogenase, and cholinesterase activities induced by 3-nitropropionic acid. These findings underscore the significant enhancement of chrysin's neuroprotective effects through glycosylation with β-d-glucose tetraacetate, positioning it as a promising candidate for use as a nutraceutical or food supplement to promote health benefits.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: