Abstract
BackgroundCurrently there is a high prevalence of humor disorders such as anxiety and depression throughout the world, especially concerning advanced age patients. Aniba riparia (Nees) Mez. (Lauraceae), popular known as “louro”, can be found from the Amazon through Guianas until the Andes. Previous studies have already reported the isolation of alkamide-type alkaloids such as riparin III (O-methyl-N-2,6-dyhydroxy-benzoyl tyramine) which has demonstrated anxiolytic and antidepressant-like effects in high doses by intraperitoneal administration.MethodsExperimental protocol was conducted in order to analyze the anxiolytic-like effect of riparin III at lower doses by intravenous administration to Wistar rats (Rattus norvegicus) (n = 5). The experimental approach was designed to last 15 days, divided in 3 distinct periods of five days: control, anxiogenic and treatment periods. The anxiolytic-like effect was evaluated by experimental behavior tests such as open field and elevated plus-maze test, combined with urine metabolic footprint analysis. The urine was collected daily and analyzed by 1H NMR. Generated data were statistically treated by Principal Component Analysis in order to detect patterns among the distinct periods evaluated as well as biomarkers responsible for its distinction.ResultsIt was observed on treatment group that cortisol, biomarker related to physiological stress was reduced, indicating anxiolytic-like effect of riparin III, probably through activation of 5-HT2A receptors, which was corroborated by behavioral tests.Conclusion1H NMR urine metabolic footprint combined with multivariate data analysis have demonstrated to be an important diagnostic tool to prove the anxiolytic-like effect of riparin III in a more efficient and pragmatic way.
Highlights
There is a high prevalence of humor disorders such as anxiety and depression throughout the world, especially concerning advanced age patients
The results have demonstrated that there was no significant difference among control period (CP), anxiogenic period (AP) and treatment period (TP) groups, considering the number of entries on open arms
The results suggest that riparin III has effect over the 5HT2A receptors from amygdala [76], once this drug has demonstrated its anxiolytic-like effect on open field tests, by decreasing activity parameters, such as grooming and rearing (Fig. 3 B e D) [77]; it has presented no effect over reward system which has the 5-HT1B, 5HT2A and 5-HT2C receptors [78]
Summary
There is a high prevalence of humor disorders such as anxiety and depression throughout the world, especially concerning advanced age patients. Previous studies have already reported the isolation of alkamide-type alkaloids such as riparin III (O-methyl-N-2,6-dyhydroxy-benzoyl tyramine) which has demonstrated anxiolytic and antidepressant-like effects in high doses by intraperitoneal administration. (Lauraceae) is a popular plant well known as “louro”, found from the Amazon and Guianas until the Andes, rich in Alkamide-type alkaloids, which were isolated from the green fruit of this species, such as riparin III (O-methyl-N-2,6-dyhydroxybenzoyl tyramine) [12,13,14]. Previous in vivo studies have demonstrated anxiolytic and antidepressant-like effects of riparin III in high doses by intraperitoneal and oral administration [15]. Semisynthetic chemicals (riparin A) have proved its anxiolytic-like effects [20], supporting the important pharmacological activity of riparin and its variations
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