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. 2025 Apr;398(4):4095-4109.
doi: 10.1007/s00210-024-03526-5. Epub 2024 Oct 16.

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

Robbert Mota Pereira  1 , Hericles Mesquita Campos  1 , Pâmela Yasmin de Oliveira Ferreira  1 , Nkaa Uchenna  1 , Yohanny Souza Silva  1 , Victor Ifeanyi Okoh  1 , Letizia Pruccoli  2 , Evilanna Lima Arruda  3 , Luciano Morais Lião  4 , Pedro Augusto Alves Mota  5 , Jacqueline Alves Leite  1 , Raphaela de Castro Georg  1 , David Henriques da Matta  5 , Fernanda Cristina Alcantara Dos Santos  1 , Elson Alves Costa  1 , Andrea Tarozzi  2 , Ricardo Menegatti  3 , Paulo César Ghedini  6   7
Affiliations

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

Robbert Mota Pereira et al. Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr.

Abstract

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.

Keywords: Anticholinesterase; Antioxidant; Glycosylated chrysin; Huntington disease; Neuroprotection; Nutraceutical.

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Conflict of interest statement

Declarations. Ethical approval: This study was conducted in accordance with the ARRIVE (NC3Rs – National Center for Replacement, Refinement, and Reduction of Animals in Research) guidelines and in compliance with the recommendations outlined in the National Research Council’s Guide for the Care and Use of Laboratory Animals (8th edition). All protocols employed in the study received approval from the Ethics Committee on Animal Use at the Federal University of Goiás (CEUA-UFG), as declared in the amendment protocol number CEUA-UFG 053/2016, dated 03/07/2022. Competing interests: The authors declare no competing interests.

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