MULTITARGET THERAPEUTIC POTENTIAL OF VALERIANA CLARIONIFOLIA EXTRACT FOR ALZHEIMER'S DISEASE AND COMORBIDITIES: IN VITRO AND IN VIVO EVALUATIONS.

CAROLINA MARCUCCI; MARINA RADEMACHER; VALENTINA PASTORE; VICTORIA SUAREZ; FABIOLA KAMECKI; HERNAN BACH; RAFAEL RICCO; NATALIA COLETTIS; MARIEL MARDER.

MEDICINA (BUENOS AIRES)

MEDICINA (BUENOS AIRES)

Lugar: Buenos Aires; Año: 2023

0025-7680

Alzheimer’s disease (AD) is a neurodegenerative disordercharacterized by abnormal protein accumulation(β-amyloid, tau), oxidative stress, and neurotransmitterimbalances, particularly acetylcholine. In this study, thehydroalcoholic extract of the underground parts of Valerianaclarionifolia, a native valerian species from PatagoniaArgentina known as “Ñamkulawen” in Mapuzungumlanguage, was evaluated. The extract’s ability to inhibitacetylcholinesterase/butyrylcholinesterase (AChE/BChE) in mouse brain/plasma homogenates (Ellman’smethod), human recombinant monoamine oxidases Aand B (MAO A and MAO B) (Amplex Red method), β-amyloidpeptide aggregation (thioflavin T method), and itsantioxidant effects (TBARS, DPPH and ABTS assays)were assessed in vitro. Furthermore, in vivo behavioraland cognitive evaluations were conducted on male Swissmice using chronic treatments with 50 mg/kg/day of the extract in drinking water for 30 days. The hydroalcoholicextract inhibited murine AChE (IC50(IC95%) 1.29 (0.81-2.05) mg/ml) but displayed stronger inhibition of BChE inboth mice (IC50 1.86 (1.43-2.43) μg/ml) and humans (IC500.44 (0.36-0.54) mg/ml). Additionally, it exhibited significantinhibition of Aβ1-42 aggregation (82% at 0.1 mg/ml),but was unable to inhibit human MAO-A or MAO-B. Thechronic treatment of mice with V. clarionifolia extract inducedanxiolytic/sedative effects (plus maze and openfield assays), improved spatial working memory (y-mazetest), and antidepressant-like effects (tail suspensiontest), along with a significant decrease in AChE activity intheir brains (ex vivo) compared to mice that drank water.In conclusion, V. clarionifolia demonstrates multitargettherapeutic potential for the treatment of Alzheimer’s diseaseand its comorbidities.