Comparative Metabolomic Analysis and Antinociceptive Effect of Methanolic Extracts from Salvia cinnabarina, Salvia lavanduloides and Salvia longispicata

Mexico is considered one of the countries with the greatest diversity of the <i>Salvia</i> genus. A significant percentage of its species are known for their use in traditional medicine, highlighting their use as an analgesic. The objective of this work was to determine the chemical composition of the methanolic extracts of <i>S. cinnabarina</i>, <i>S. lavanduloides</i> and <i>S. longispicata</i> through untargeted metabolomics, as well as the in vivo evaluation of the antinociceptive effect and acute oral toxicity. The chemical profiling was performed using ultra-high performance liquid chromatography coupled with a high-resolution mass spectrometry (UPLC-ESI^+/--MS-QTOF) system and tentative identifications were performed using a compendium of information on compounds previously isolated from Mexican species of the genus. Pharmacological evaluation was carried out using the formalin test and OECD guidelines. The analysis of the spectrometric features of the mass/charge ratios of the three salvias shows that a low percentage of similarity is shared between them. Likewise, the putative identification allowed the annotation of 46 compounds, mainly of diterpene and phenolic nature, with only four compounds shared between the three species. Additionally, the extracts of the three salvias produced a significant antinociceptive effect at a dose of 300 mg/kg administered orally and did not present an acute oral toxicity effect at the maximum dose tested, indicating a parameter of LD₅₀ > 2000 mg/kg. The exploration of the chemical profile of the three salvias by untargeted metabolomics shows that, despite being species with antinociceptive potential, they have different chemical profiles and therefore different active metabolites.