Bioprospecting-based untargeted metabolomics identifies alkaloids as potential anti-inflammatory bioactive markers of Ocotea species (Lauraceae)

Albert Katchborian-Neto; Karen de Jesus Nicácio; Jonas C Cruz; Paula Carolina Pires Bueno; Michael Murgu; Danielle F Dias; Marisi G Soares; Ana C C Paula; Daniela A Chagas-Paula

doi:10.1016/j.phymed.2023.155060

Bioprospecting-based untargeted metabolomics identifies alkaloids as potential anti-inflammatory bioactive markers of Ocotea species (Lauraceae)

Phytomedicine. 2023 Nov:120:155060. doi: 10.1016/j.phymed.2023.155060. Epub 2023 Sep 3.

Authors

Albert Katchborian-Neto¹, Karen de Jesus Nicácio², Jonas C Cruz³, Paula Carolina Pires Bueno⁴, Michael Murgu⁵, Danielle F Dias¹, Marisi G Soares¹, Ana C C Paula⁶, Daniela A Chagas-Paula⁷

Affiliations

¹ Institute of Chemistry, Federal University of Alfenas (UNIFAL), 37130-001, Alfenas, Minas Gerais, Brazil.
² Department of Chemistry, Federal University of Mato Grosso (UFMT), 78060-900, Cuiabá, Mato Grosso, Brazil.
³ Department of Chemistry, University of São Paulo (USP), 14040-901, Ribeirão Preto, São Paulo, Brazil.
⁴ Institute of Chemistry, Federal University of Alfenas (UNIFAL), 37130-001, Alfenas, Minas Gerais, Brazil; Leibniz Institute of Vegetable and Ornamental Crops (IGZ), Theodor-Echtermeyer-Weg 1, 14979 Großbeeren, Germany.
⁵ Waters Corporation, Alameda Tocantins 125, 27th floor, Alphaville, 06455-020, Barueri, São Paulo, Brazil.
⁶ Department of Pharmaceutical Sciences, Federal University of Juiz de Fora (UFJF), 36036-900, Juiz de Fora, Minas Gerais, Brazil.
⁷ Institute of Chemistry, Federal University of Alfenas (UNIFAL), 37130-001, Alfenas, Minas Gerais, Brazil. Electronic address: daniela.chagas@unifal-mg.edu.br.

PMID: 37717309
DOI: 10.1016/j.phymed.2023.155060

Abstract

Background: Species within the Ocotea genus (Lauraceae), have demonstrated an interesting profile of bioactivities. Renowned for their diverse morphology and intricate specialized metabolite composition, Ocotea species have re-emerged as compelling candidates for bioprospecting in drug discovery research. However, it is a genus insufficiently studied, particularly regarding anti-inflammatory activity.

Purpose: To investigate the anti-inflammatory activity of Ocotea spp. extracts and determine the major markers in this genus.

Methods: Extracts of 60 different Ocotea spp. were analysed by an ex vivo anti-inflammatory assay in human whole blood. The experiment estimates the prostaglandin E2 levels, which is one of the main mediators of the inflammatory cascade, responsible for the classical symptoms of fever, pain, and other common effects of the inflammatory process. Untargeted metabolomics analysis through liquid chromatography coupled with high-resolution mass spectrometry was performed, along with statistical analysis, to investigate which Ocotea metabolites are correlated with their anti-inflammatory activity.

Results: The anti-inflammatory screening indicated that 49 out of 60 Ocotea spp. extracts exhibited significant inhibition of PGE2 release compared to the vehicle (p < 0.05). Furthermore, 10 of these extracts showed statistical similarity to the reference drugs. The bioactive markers were accurately identified using multivariate statistics combined with a fold change (> 1.5) and adjusted false discovery rate analysis as unknown compounds and alkaloids, with a majority of aporphine and benzylisoquinolines. These alkaloids were annotated with an increased level of confidence since MS^E spectra were compared with comprehensive databases.

Conclusion: This study represents the first bioprospecting report revealing the anti-inflammatory potential of several Ocotea spp. The determination of their anti-inflammatory markers could contribute to drug discovery and the chemical knowledge of the Ocotea genus.

Keywords: Alkaloids; Anti-inflammatory; Metabolite annotation; Ocotea; Prostaglandin; UPLC-ESI-QTOF.

MeSH terms

Alkaloids* / pharmacology
Anti-Inflammatory Agents / pharmacology
Bioprospecting
Dinoprostone
Humans
Lauraceae*
Metabolomics
Ocotea*
Plant Extracts / pharmacology

Substances

Alkaloids
Anti-Inflammatory Agents
Dinoprostone
Plant Extracts