Anxiety disorders are one of the most common psychiatric illnesses in the world's population. As current pharmacotherapy is not effective and safe for all patients, seeking complementary treatment has increased. Hydrocotyle umbellata L., Araliaceae, is an herb long recognized for its anxiolytic and memory stimulant effects. This work aimed to evaluate the anxiolytic-like effects and the impact on memory of the spray-dried Hydrocotyle umbellata L. extract (SDHUE) in mice and to assess its toxicological potential. The anxiolytic-like effects of SDHUE (75, 150, 300, or 600 mg/kg) were assessed on elevated plus maze (EPM) and light-dark box (LDB) tests, and the participation of the benzodiazepine site of GABAA and 5-HT1A receptors was investigated. The memory retention of the animals was evaluated in the step-down avoidance (SDA) test, and the possible effects on learning and memory processes were assessed by ex vivo cholinesterase (ChE) activity. The toxicity assays were evaluated in terms of cytotoxicity in RAW macrophage cells, mutagenic effects by the Ames test, and embryotoxic potential using the zebrafish (Danio rerio) model. Pretreatment with flumazenil (2 mg/kg) prevented the anxiolytic-like activity induced by SDHUE. No signs of memory impairment on short- and long-term memory were detected with SDHUE treatment in the SDA test. The inhibition of ChE activity in the prefrontal cortex and hippocampus was also observed with SDHUE treatment. Moreover, it was verified an absence of apparent toxic effects. Thus, this extract may offer a promising approach for further safe and effective application in the treatment of anxiety.
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