@MASTERSTHESIS{ 2020:733339007,
 	title = {Biomarkers of anti-inflammatory and neuroprotective activity investigated by untargeted UPLC-ESI-QTOF-MS metabolomics analyses.},
 	year = {2020},
 	url = "https://bdtd.unifal-mg.edu.br:8443/handle/tede/1884",
 	abstract = "Screening for bioactive metabolites is frequently carried out in pharmaceutical drug
 discovery, and metabolomics arises as a modernized tool applied in the Natural
 Products (NP) research field for accessing plant metabolites through faster real-time
 analyses. Thus, this research aimed to perform a comprehensive LC/MS-based
 metabolomics study to investigate the anti-inflammatory potential of Ocotea
 (Lauraceae) species as well as the neuroprotective activity of the popularly known
 Ayahuasca beverage and its matrix plants. It is well known the chief role of PGE2 in
 acute inflammatory diseases, and recent publications have also indicated that higher
 COX 2 expression and increased circulating PGE2 levels play a significant role in
 cancer progression through lymphangiogenic growth. On the other hand, neural damage
 is involved in Parkinson disease (PD) progression and in other neurodegenerative
 diseases, and neuroprotective candidates for medical treatment are utterly needed to
 develop therapies that can prevent the natural progression of the disease. Thus, new
 drugs able to elicit neuroprotective activity or to inhibit PGE2 release are potential
 targets for drug discovery and development. Formerly, 60 different Ocotea species and
 the matrix plants of Ayahuasca beverage were extracted following current
 metabolomics extraction protocol. For biological activity, an ex-vivo anti-inflammatory
 screening was realised using human blood LPS-induced inflammation for quantitative
 PGE2 determination in plasma by UPLC-MS/MS. The dexamethasone and
 indomethacin were used as positive controls. For the neuroprotective evaluation, the
 Ayahuasca beverage, the extracts from its matrix plants (Banisteriopsis caapi and
 Psychotria viridis), its fractions and its main alkaloids were evaluated on the viability of
 SH-SY5Y neuroblastoma cells in an in vitro PD model. For the metabolomics analyses,
 quality control samples were prepared and all samples were subjected to UPLC-ESI-
 TOF-MS. The MS E data acquisition and treatment were performed and the dereplication
 was done using the in-house together with the UNIFI software databases (Waters ® ) and
 the Dictionary of Natural Products (DNP) for MS 1 and molecular formula match. The
 level 2 identification was performed for the Ocotea study by the obtained MS E product
 ions, which were compared with a spectral library in the literature for tentative
 compound identification. The Ayahuasca study was performed via level 3 according to
 current metabolomics standards. The treated data were analysed by multivariate
 statistical analysis for biomarkers investigation. The metabolic fingerprints generated
 allowed the dereplication of the majority of the extracted compounds found on the
 evaluated extracts. Under the Ocotea metabolomics study, it was observed
 quantitatively more aporphine alkaloids and glycosylated flavonoids in most of the
 Ocotea extracts. Moreover, 12 out of 60 Ocotea spp. evaluated have exhibited high
 satisfactory PGE2 inhibition. Regarding the neuroprotective evaluation, the lower doses
 of the active samples from Ayahuasca and its base plants showed to be able to stimulate
 neuronal cell proliferation and/or display the most efficacious neuroprotection profile.
 Intriguingly, the hydroalcoholic fractions exhibited enhanced neuroprotective effects
 when compared to other samples and isolated alkaloids. The general metabolomic
 analysis allowed determining the biomarkers of anti-inflammatory and neuroprotective
 activity, besides possibly new compounds with no hits in chemical databases. The
 biomarkers findings of this research might be potential neuroprotective or anti-
 inflammatory lead-structures. In addition, this is the first report regarding the chemical
 composition and bioactivity of several endemic Ocotea spp. of the Brazilian territory.
 And also, this work found that the Ayahuasca beverage and its base plants have
 potential applicability for PD treatment and other neurodegenerative diseases.",
 	publisher = {Universidade Federal de Alfenas},
 	scholl = {Programa de Pós-Graduação em Química},
 	note = {Instituto de Química}
}