Neuroprotective Effect of Yucca schidigera Roezl ex Ortgies Bark Phenolic Fractions, Yuccaol B and Gloriosaol A on Scopolamine-Induced Memory Deficits in Zebrafish

Abstract

Y. schidigera contains a number of unusual polyphenols, derivatives of resveratrol and naringenin, called spiro-flavostilbenoids, which have potent in vitro anti-inflammatory, antioxidant, and moderate cholinesterase inhibitory activities. To date, these compounds have not been tested in vivo for the treatment of neurodegenerative diseases. The aim of the present study was to evaluate the effects of both single spiro-flavostilbenoids (yuccaol B and gloriosaol A) and phenolic fractions derived from Y. schidigera bark on scopolamine-induced anxiety and memory process deterioration using a Danio rerio model. Detailed phytochemical analysis of the studied fractions was carried out using different chromatographic techniques and Nuclear Magnetic Resonance (NMR). The novel tank diving test was used as a method to measure zebrafish anxiety, whereas spatial working memory function was assessed in Y-maze. In addition, acetylcholinesterase/butyrylcholinesterase (AChE/BChE) and 15-lipooxygenase (15-LOX) inhibition tests were performed in vitro. All pure compounds and fractions under study exerted anxiolytic and procognitive action. Moreover, strong anti-oxidant capacity was observed, whereas weak inhibition towards cholinesterases was found. Thus, we may conclude that the observed behavioral effects are complex and result rather from inhibition of oxidative stress processes and influence on cholinergic muscarinic receptors (both 15-LOX and scopolamine assays) than effects on cholinesterases. Y. schidigera is a source of substances with desirable properties in the prevention and treatment of neurodegenerative diseases.

Spiro-Flavonoids in Nature: A Critical Review of Structural Diversity and Bioactivity

“…These compounds interacted similarly with the peripheral anionic site of AChE and were located deep in the catalytic site of BChE [ 7 ]. The neuroprotective effect of yuccaol B and gloriosaol A was also confirmed in vivo using adult zebrafish models [ 106 ]. The Y-maze test was used to assess the function of spatial working memory function, while the novel tank diving test was used to measure anxiety in Danio rerio .…”

“…That is, diastereoisomeric pairs of compounds 36 – 37 , 38 – 39 , and 40 – 41 are formed as a result of a regiospecific coupling of the naringenin radical with a stilbene-type radical (resveratrol or THMS). Interestingly, compounds 38 – 41 undergo further coupling with the naringenin radical to give compounds 44 – 48 and probably also form more complex polymeric structures [ 106 ] ( Scheme 4 ).…”

“…Spiro-derivatives were shown to exert a broad range of biological activities, such as antioxidant, anti-inflammatory, neuroprotective, antimicrobial, antidiabetic, anticancer/cytotoxic, antiviral, antimalarial, etc. [ 4 , 106 , 110 , 112 , 113 , 114 ]. Their pharmacological potential is attributed directly to their inherent three-dimensionality, versatility, rigidity of spiro-cyclic scaffolds, good balance between flexibility and conformational restriction, and structural similarity to important pharmacophore centers [ 110 , 113 , 115 ].…”

“…The 15-LOX (lipoxygenase) inhibition assay was used to test the ability of 37 and 44 isolated from the bark of Y. schidigera to protect polyunsaturated acids from peroxidation [ 106 ]. Their antioxidant activity was higher (EC 50 = 9.66 µg/mL for yuccaol B, EC 50 = 12.34 µg/mL for gloriosaol A) compared to the positive control: ascorbic acid (EC 50 = 21.52 µg/mL) [ 106 ].…”

Teleosts as behaviour test models for social stress

“…Different protocols have been utilized in Y-maze. The commonly used tests are novel arm recognition test ( Cognato et al, 2012 ; Pecio et al, 2022 ) and spontaneous alternation test ( Fontana et al, 2021a , c ). The novel arm recognition test usually includes two sessions.…”