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dc.contributor.authorVIEIRA, SÍLVIO MANFREDO
dc.contributor.authorSILVA, RANGEL LEAL
dc.contributor.authorLEMOS, HENRIQUE PAULA
dc.contributor.authorAMORIM, RODRIGO CÉSAR DAS NEVES
dc.contributor.authorSILVA, ELLEN CRISTINA COSTA
dc.contributor.authorREINACH, PETER SOL
dc.contributor.authorCUNHA, FERNANDO QUEIRÓZ
dc.contributor.authorAdrian Martin Pohlit
dc.contributor.authorCUNHA, THIAGO MATTAR
dc.description.abstractInfusions of Picrolemma sprucei roots, stems and leaves are used in traditional medicine throughout the Amazon region from the Guianas to Brazil and Peru in the treatment of gastritis, intestinal helminths and malaria. As there are no studies describing its mode of action in providing a gastroprotective effect, we determined herein that one of the main constituents found in P. sprucei infusions, the quassinoid isobrucein B (IsoB), reduces some of the pathophysiological effects in a mouse model of non-steroidal anti-inflammatory drug (NSAID)-induced gastritis and provides mechanisms of action. Then, IsoB (1.17 g) was isolated from the roots and stems (6.5 kg) of P. sprucei. Its structure was confirmed by 1D and 2D 1H and 13C NMR, ESI-tof-MS, IR and UV. C57BL/6 strain mice were subcutaneously injected with IsoB (0.5–5 mg kg− 1) or vehicle before oral administration of indomethacin and sacrificed later at different time points. Gastric damage was assessed by measuring lesion length. Leukocyte migration was evaluated based on leukocyte rolling and adhesion using intravital microscopy in the mesenteric microcirculation and tissue MPO activity. Stomach extract cytokine (TNFα, IL-1β and KC/CXCL1) and prostaglandin E2 (PGE2) levels were measured by ELISA and RIA, respectively. IsoB pre-treatment (0.5–5.0 mg kg− 1) significantly reduced the formation of indomethacin-induced stomach lesions in a dose-dependent manner. The decrease in stomach lesions was associated with less observed leukocyte rolling, decreased leukocyte adhesion and less neutrophil infiltration (MPO activity). IsoB (1 mg kg− 1) pre-treatment did not prevent indomethacin-induced decreases in stomach PGE2 levels. However, IL-1β and KC/CXCL1 levels were inhibited by this same IsoB dosage, whereas TNF-α was unchanged. IsoB may be a prototypic compound to provide protective effects against NSAID-induced gastritis and possibly other gastropathies. Moreover, IsoB gastroprotective action may be due to a reduction in IL-1β and KC/CXCL1 production/release and leukocyte rolling, adhesion and migration.
dc.subjectisobruceína B
dc.titleGastro-protective effects of isobrucein B, a quassinoid isolated from Picrolemma sprucei
dc.publisher.periodicoFitoterapia (Milano, 1934) (Cessou em 1960. Foi fundido com ISSN 1971-5498 Fitoterapia. Edizione Farmaceutica; ISSN 1971-5501 Fitoterapia. Edizione Me
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