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Antidepressant and anxiolytic compounds isolated from Salvia elegans interact with serotonergic drugs

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Abstract

Salvia elegans belongs to a genus plants with biological activities in central nervous system. In this work, the purpose was to evaluate the anxiolytic and antidepressant effects of fractions and compounds isolated from S. elegans and its interaction with serotoninergic drugs by using behavioral tests in mice. Fractions from aerial parts of S. elegans were obtained by column chromatography, SeF1, SeF2, SeF3, and SeF4. Each of them was administered to 25 mg/k in ICR mice subject to forced swimming test (FST), or elevated plus maze test (EPM), or open field test (OFT). The most active fractions were chemically separated until compounds, which were analyzed as anxiolytic or antidepressant and the coadministration of these treatments with 5-HT1A and 5-HT2 drugs was measured in the different biological tests. All fractions were anxiolytic and antidepressant, oleanolic acid (OA) was found in SeF2, and from SeF3, a mixture of terpenes was found; a GC–MS analysis confirmed the presence of two main compounds: rosifoliol and agaraspirol (TM, mixture of terpenes). TM (doses-response curve, 0.01, 0.1, 0.5, 1.0, and 2.0 mg/kg) and OA (5 mg/kg) were also evaluated demonstrating an antidepressant and anxiolytic effect, respectively. The combination of TM (0.5 mg/kg) with 8-OH (selective 5-HT1A receptor agonist) induced an increment of antidepressant activity, while with the antagonist WAY-100635, the effect diminished. But with DOI (5-HT1c/5-HT2 receptor agonist), there was no change, and with KET (5-HT2 receptor antagonist), the activity was increased. When OA is co-administered with 8-OH or with DOI, the anxiolytic activity of this terpene, diminished; but with the combination with antagonists, the effect of OA shows no change. TM and OA were antidepressant and anxiolytic, respectively, on mice exposed to different tests, and these are able to interact with serotoninergic drugs.

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Abbreviations

FST:

Forced swimming test

EPM:

Elevated plus maze

OFT:

Open field test

5-HT:

Serotonin

5-HT1A :

Serotonin receptor type 1A

5-HT2 :

Serotonin receptor type 2

8-OH:

8-Hydroxy-2-(di-n-propylamino)tetralin

WAY:

N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide

KET:

Ketanserine

DOI:

1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane

SeF1:

Fraction 1 from S. elegans

SeF2:

Fraction 2 from S. elegans

SeF3:

Fraction 3 from S. elegans

SeF4:

Fraction 4 from S. elegans

OA:

Oleanolic acid

TM:

Agarospirol/rosifoliol mixture

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Funding

This work was partially supported by Fondo de Investigación en Salud-IMSS number FIS/IMSS/PROT/PRIO/14/029. Martínez-Hernández GB is grateful for the fellowship from CONACyT 558749 and for the complementary support from IMSS 99186327.

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Authors and Affiliations

  1. Centro de Investigación Biomédica del Sur, Instituto Mexicano del Seguro Social (IMSS), Argentina 1, 62790, Xochitepec, Morelos, México

    Gabriela Belen Martínez-Hernández, Enrique Jiménez-Ferrer, Manases González-Cortazar, Jaime Tortoriello, Gabriela Vargas-Villa & Maribel Herrera-Ruiz

  2. Doctorado en Ciencias Biológicas Y de La Salud, División de Ciencias Biológicas Y de La Salud, Universidad Autónoma Metropolitana (UAM), México City, México

    Gabriela Belen Martínez-Hernández

  3. Departamento de Ciencias de La Salud, División de Ciencias Biológicas Y de La Salud, Universidad Autónoma Metropolitana—Iztapalapa, Av. San Rafael Atlixco No.186, Col. Vicentina C.P.09340, Iztapalapa, México D.F., México

    Gabriela Belen Martínez-Hernández & Rubén Román-Ramos

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  1. Gabriela Belen Martínez-Hernández
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  2. Enrique Jiménez-Ferrer
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  3. Manases González-Cortazar
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  6. Gabriela Vargas-Villa
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Contributions

The authors declare that all data were generated in-house and that no paper mill was used.

Antidepressant and anxiolytic behavioral assays, extraction, chromatographic assays, and chemical preparation of samples for S. elegans were demonstrated by M-HGB and V-VG. Experimental design, statistical analysis, manuscript preparation, and pharmacologic analysis were demonstrated by H-RM, J-FE, and R-RR. Chemical UPLC and gases-M analysis were demonstrated by M-GC and TJ.

Corresponding author

Correspondence to Maribel Herrera-Ruiz.

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Martínez-Hernández, G.B., Jiménez-Ferrer, E., González-Cortazar, M. et al. Antidepressant and anxiolytic compounds isolated from Salvia elegans interact with serotonergic drugs. Naunyn-Schmiedeberg's Arch Pharmacol 394, 2419–2428 (2021). https://doi.org/10.1007/s00210-021-02155-6

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