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

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 MSE 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.

Occurrence of trace elements in print paper products: Non-carcinogenic risk assessment through dermal exposure.

Over time, the risk assessment of dermal exposure to pollutants in print paper products has received considerable attention. Most studies have focused on organic pollutants, especially bisphenol A (BPA). However, little is known about the levels of trace elements in print paper products, despite the knowledge that these elements are components of printing inks and toners. This study was aimed at determining the concentrations of trace elements in 5 types of paper products, namely bulletins, magazines, special events program booklets, handbills, and newspapers. The average daily intake (ADI) of each element was subsequently estimated through dermal exposure to the papers. The detection frequency of the elements of interest was high (nearly 100%) in most paper products, with the exception of chromium, whose detection was low. In contrast, Ag was not detected in any sample. The levels of the elements in the paper products were low and comparable to those found in other personal and consumer products with the potential for skin contact. The range values of estimated ADIs were 1.70-3.90E-08, 2.30-18.2E-10, 2.60-16.4E-09, 3.65-5.75E-08, 1.29-4.38E-08, 6.23-15.6E-10, 1.51-2.80E-10, 1.43-9.16E-09, 0.00-9.47E-09, and 4.68-220E-08 mg/kg bw/day for Mn, Co, Ni, Cu, Zn, As, Cd, Pb, Cr and Fe respectively. These values were well below the dermal standard reference doses (RfD) for each element. The present results indicate that dermal exposure to trace elements from print paper products was low and does not pose significant risks for toxic (non-carcinogenic) effects on humans.