Chrysin, but not flavone backbone, decreases anxiety-like behavior in animal screens

Abstract

Chrysin (5,7-dihydroxyflavone), a nutraceutical flavonoid present in diverse plants, has a backbone structure shared with the flavone backbone, with additional hydroxyl groups that confers its antioxidant properties and effects at the GABAA receptor complex. However, whether these effects are due to the hydroxyl groups is unknown. Here we report the effects of chrysin or the flavone backbone (1 mg/kg) in rats subjected to the elevated plus-maze and the locomotor activity test, as well as in the zebrafish evaluated in light/dark model. Chrysin, but not flavone, increased entries and time in the open arms of the elevated plus-maze, as well as time on white compartment of the light/dark model in zebrafish. These effects were comparable to diazepam, and were devoid of motor effects in both tests, as well as in the locomotor activity test. On the other hand, flavone decreased risk assessment in the light/dark test but increased rearing in the locomotor activity test in rats, suggesting effects threat information gathering; important species differences suggest new avenues of research. It is suggested that the specific effects of chrysin in relation to flavone include more of a mechanism of action in which in addition to its action at the GABAA/benzodiazepine receptor complex also could be involved its free radical scavenging abilities, which require specific research.

Zebrafish as a Useful Tool in the Research of Natural Products With Potential Anxiolytic Effects

“…This variation may be the consequence of differences in methodology and tank characteristics; for example, the light intensity: fish spend more time exploring the white compartment when light is around 250 lux, while in lights around 500 lux, fish prefer the dark compartment (Stewart et al, 2011); for that reason, protocol characteristics must be considered in the interpretation of the findings. In the present review, some literature did not specify light intensity, but most of the quoted studies (de Carvalho et al, 2019;Duarte et al, 2019;German-Ponciano et al, 2020;Zenki et al, 2020) illuminated the light/dark chamber thanks with an environmental light bulb of 75 Watts located above the aquarium top (1.8 m), producing a constant average of 975 lux, based on Maximino et al (2010a,b).…”

Pharmacological, Neurochemical, and Behavioral Mechanisms Underlying the Anxiolytic- and Antidepressant-like Effects of Flavonoid Chrysin

“…It has the potential to be used as an alternative in the treatment of metabolic, cardiovascular, and neuropsychiatric disorders [ 10 ]. In addition, the presence of hydroxyl groups in the backbone of chrysin has been associated with its anxiolytic-like effects [ 23 ]. Chrysin, but not the flavone backbone, decreases anxiety-like behavior in rats and zebrafish, suggesting that the presence of hydroxyl groups in its basic structure is indispensable for producing anxiolytic-like effects in pre-clinical research [ 23 ].…”

“…Similarly, anxiolytic-like effects of chrysin in mammals (mice and rats) have also been reported in non-mammalian organisms (zebrafish). Chrysin at 1 mg/kg decreased anxiety-like behavior in rats and zebrafish, similar to diazepam [ 23 ]; however, treatment with a flavone backbone at 1 mg/kg was devoid of anxiolytic-like effects in both rats and zebrafish, suggesting that the presence of hydroxyl groups in its basic structure could be indispensable to produce anxiolytic-like effects [ 23 ].…”

Recent Applications of Heteropolyacids and Related Compounds in Heterocycle Synthesis. Contributions between 2010 and 2020

“…Thus, the structure of the flavones (oxo group in C-4 and conjugated B and C rings) present in cereals is associated with anti-inflammatory properties, improvement in insulin sensitivity, and a greater interaction with transporters of the intestinal membrane [154,155]. Similarly, neuropharmacological actions have been attributed to flavonoids such as chrysin present in honey [156], and there are many studies on the anticancer activity of natural flavonoid compounds [157]. This has led to consider chromones as the central backbone in a number of functional organic compounds, and in the development of new drugs.…”