ABSTRACT
Alcohol use disorder (AUD) is characterized by a set of behavioral, cognitive, nutritional, and physiological phenomena derived from the uncontrolled use of alcoholic beverages. There are cases in which AUD is associated with anxiety disorder, and when untreated, it requires careful pharmacotherapy. Blue Calm® (BC) is a food supplement indicated to aid restorative sleep, which has traces of medicinal plant extracts, as well as myo-inositol, magnesium bisglycinate, taurine, and L-tryptophan as its main chemical constituents. In this context, this study aimed to evaluate the potential of the BC in the treatment alcohol withdrawal-induced anxiety in adult zebrafish (aZF). Initially, BC was submitted to antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl radical. Subsequently, the aZF (n = 6/group) were treated with BC (0.1 or 1 or 10 mg/mL; 20 µL; p.o.), and the sedative effect and acute toxicity (96 h) were evaluated. Then, the anxiolytic-like effect and the possible GABAergic mechanism were analyzed through the Light & Dark Test. Finally, BC action was evaluated for treating alcohol withdrawal-induced anxiety in aZF. Molecular docking was performed to evaluate the interaction of the major chemical constituents of BC with the GABAA receptor. BC showed antioxidant potential, a sedative effect, was not toxic, and all doses of BC had an anxiolytic-like effect and showed potential for the treatment of alcohol withdrawal-induced anxiety in aZF. In addition to the anxiolytic action, the main chemical constituents of BC were confirmed in the molecular docking, thus suggesting that BC is an anxiolytic that modulates the GABAergic system and has pharmacological potential for the treatment of alcohol withdrawal-induced anxiety.
Subject(s)
Alcoholism , Anti-Anxiety Agents , Substance Withdrawal Syndrome , Animals , Zebrafish/physiology , Anti-Anxiety Agents/pharmacology , Anti-Anxiety Agents/therapeutic use , Anxiety/chemically induced , Anxiety/drug therapy , Anxiety/psychology , Alcoholism/drug therapy , Molecular Docking Simulation , Substance Withdrawal Syndrome/drug therapy , Receptors, GABA-A , Antioxidants/pharmacology , Antioxidants/therapeutic use , Anxiety Disorders/drug therapy , Dietary Supplements , Hypnotics and SedativesABSTRACT
ABSTRACT Croton zehntneri Pax & K. Hoffm., Euphorbiaceae, or "canela-de-cunhé" is used in the Northeast Brazil to treat several diseases. Leaves and aerial parts of C. zehntneri are rich in volatile oil of high potential therapeutic. This study aimed to investigate volatile oil systemic toxicity after per oral treatment in rats. Volatile oil characterization (gas chromatography and mass spectrometry) showed 85.7% anethole and 4.8% estragole. Male Wistar rats (116-149 g) were treated with volatile oil (250 mg/kg p.o.) during ten weeks and evaluated for the following parameters: survival; food and water intake; body mass; absolute/relative organs weight; hemogram; plasma biochemical dosage; organs morphology. Volatile oil did not alter animal water and food consumption or the relative/absolute weight of most organs, but animals gained less weight. Volatile oil did not alter function biomarkers of pancreas, kidney, heart or liver, but increased plasma gamma-glutamyltranspeptidase (liver biomarker) and decreased uric acid (kidney biomarker). Although volatile oil had caused discrete morphological alterations in some organs, it did not induce architectural changes in these organs. In conclusion, the sub-acute per oral treatment with volatile oil no longer than ten weeks in rats offers small toxicity at doses below 250 mg/kg.