The use of herbal medicine in Alzheimer?s disease. Valeriana carnosa sm. (Caprifoliacea), a perspective

MARCUCCI C, ; RADEMACHER M,; BACH HG,; KAMECKI F,; KNEZ D, ; WAGNER ML,; COLETTIS N,; RICCO RA,; MARDER M.

Congreso; V Congreso Internacional en Medicina Traslacional; 2021

Background and aimsAlzheimer's disease is a neurodegenerative disorder associated with abnormal accumulation of proteins (β-amyloid, tau), oxidative stress, alterations in neurotransmitter levels (mainly acetylcholine), among others. Our country harbors thousands of plant species, some of which are used in popular medicine even lacking from scientific information. Our hypothesis is that our native valerian species contain unexplored compounds with multiple biological activities on the CNS. MethodsWe present here a study of the hydroalcoholic extract from underground parts of Valeriana carnosa (Caprifoliaceae), a ?valerian? from Patagonia Argentina, known as ?Ñamkulawen? in Mapuzungum language. Its ability to inhibit acetyl/butyrylcholinesterase (AChE/BChE) enzymes from mouse brain homogenate/plasma (Ellman's method), recombinant human monoaminoxidase A and B (MAO A and MAO B) (Amplex red method), aggregation of amyloid β peptide (thioflavin T method) and antioxidant effect (DPPH and ABTS assay) were evaluated in vitro. Anxiolytic/sedative properties (holeboard and locomotor activity tests), effect on spatial working memory (Y-maze test) and anti-depressant like activity (Tail suspension test) were evaluated in vivo in mice (Swiss male, 25.30 g) in chronic treatments (100 mg/kg/day, extract in drinking water) (CICUAL FFyB: 02052016-63).ResultsThe extract was able to inhibit both AChE (IC50(CI95%): 7.26 (2,94-17,92) mg/ml) and BChE (IC50(CI95%): 1,16 (0,95-1,42) mg/ml). It also inhibited Aβ1-42 aggregation (0.1 mg/ml, 60%). A direct relationship between antioxidant capacity and phenol content was observed. Furthermore, V. carnosa extract selectively inhibited hMAO A (IC50(CI95%): 343 (263-448) μg/ml) over hMAO B. Then the in vivo (mice) effect of the extract was evaluated under chronic treatment (over 1 month). Anxiolytic/sedative properties and effect on spatial working memory were evaluated. Finally, mice brain AChE activity was determined. The daily intake of the extract neither produced anxiolytic-like effects, nor did it modify the locomotor activity of the mice at the dose tested. An improvement in the spatial working memory and an anti-depressant like effect of the animals treated with the extract was observed, as well as a significant decrease in AChE activity in their brains. ConclusionsV. carnosa is a multitarget therapeutic tool for Alzheimer's disease treatment and its comorbidities.