Evaluation of spontaneous exploratory and anxiety-related behaviors of mice treated with gymnopilins obtained from the mushroom Gymnopilus imperialis (Agaricomycetes, Basidiomycota)

• Published in: Toxicon (Oxford) 2024-03, Vol.240, p.107626-107626, Article 107626
• Main Authors: Caldas, Lhaís Araújo, Muratori, Beatriz Gangale, Soliani, Andressa Gabriela, Cerutti, Suzete Maria, Sartorelli, Patrícia
• Format: Article
• Language: English
• Subjects: Anxiolytic effects; biosynthesis; class; Dereplication; diazepam; dose response; Gymnopilins; Gymnopilus; isoprene; liquid chromatography; mass spectrometry; memory; methylene chloride; mushrooms; neurotoxicity; neurotransmitters; Object recognition memory; secondary metabolites; species; Spontaneous locomotor activity
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2024.107626

Gymnopilins are long chain oligoisoprenoids produced through the condensation of isoprene units from MEV and MEP biosynthetic pathways. In Gymnopilus, these carotenoid-like molecules are recognized as major compounds in some species. In the present study, oligoisoprenoids derived from gymnopilins were dereplicated from Gymnopilus imperialis, a mushroom-forming basidiomycete, using liquid chromatographic coupled with high-resolution mass spectrometry (tandem LC-HRMS/MS) and GNPS. From the dichloromethane extract (Gym-DCM) of G. imperialis we annotated 3 oligoisoprenoids from the GNPS molecular library spectra and 15 analogs from the curation of the molecular networking. Data from NMR spectroscopic of the extract confirmed the annotation of the metabolites. Based on the literature data suggesting the neurotoxic effect of gymnopilins, we investigated the effects of the administering different doses of gymnopilin extracts (1, 4 or 10 mg/kg) and diazepam (4 mg/kg) on the acquisition of object recognition memory (ORM) in mice. By studying novel object recognition memory (ORM), a type of non-aversive memory. ORM was assessed based on the total time of spontaneous exploration of both objects, the discrimination index (DI), and the frequency of contact with both objects. Our present findings reveal, for the first time, that gymnopilins treatment before training modulates ORM in a dose-dependent manner. It is also suggested that differential effects on memory might be related to differential effects on GABAA receptors but do not exclude its effects in other neurotransmitter systems. Another class of secondary metabolites, alkaloids, might modulate AChR, which is essential for maintaining object recognition memory over time. [Display omitted] •Dereplication of G. imperialis by LC-HRMS/MS allowed the annotation of eighteen oligoisoprenoids derived from gymnopilins.•Treatment of mice with gymnopilins at a higher dose did not prevent the acquisition and retrieval of memory for objects.•Gymnopilins in all doses did not modulate anxiety-like behavior in mice, as well as did not result in sedative effects.•Gymnopilins treatment in mice before training modulates ORM in a dose-dependent manner.