Gastro-protective effects of isobrucein B, a quassinoid isolated from Picrolemma sprucei

Manfredo Vieira, Silvio; Silva, Rangel Leal; Lemos, Henrique Paula; Amorim, Rodrigo C.N.; Silva, Ellen Cristina Costa; Reinach, Peter Sol; Cunha, Fernando Queiroz; Pohlit, Adrian Martin; Cunha, Thiago Mattar

Artigo

Gastro-protective effects of isobrucein B, a quassinoid isolated from Picrolemma sprucei

Infusions 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 gastroprotec...

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Autor principal:	Manfredo Vieira, Silvio
Outros Autores:	Silva, Rangel Leal, Lemos, Henrique Paula, Amorim, Rodrigo C.N., Silva, Ellen Cristina Costa, Reinach, Peter Sol, Cunha, Fernando Queiroz, Pohlit, Adrian Martin, Cunha, Thiago Mattar
Grau:	Artigo
Idioma:	English
Publicado em:	Fitoterapia 2020
Assuntos:	Cxcl1 Chemokine Interleukin-1beta Isobrucein B Nonsteroid Antiinflammatory Agent Prostaglandin E2 Prostaglandin Synthase Protective Agent Quassinoid Derivative Tumor Necrosis Factor-alpha Unclassified Drug Cytokine Indometacin Isobrucein B Nonsteroid Antiinflammatory Agent Plant Extract Prostaglandin E2 Quassinoid Derivative Adult Animals Experiment Animals Model Animals Tissue Capillary Wall Carbon Nuclear Magnetic Resonance Controlled Study Drug Mechanism Enzyme-linked Immunosorbent Assay Gastritis Leukocyte Adherence Leukocyte Migration Leukocyte Rolling Male Microcirculation Mouse Neutrophil Chemotaxis Nonhuman Pathophysiology Picrolemma sprucei Plant Root Plant Stem Priority Journal Prostaglandin Synthesis Protection Proton Nuclear Magnetic Resonance Simaroubaceae Stomach Injury Stomach Lesion Animals C57bl Mouse Cell Adhesion Chemical Structure Chemically Induced Chemistry Disease Model Dose Response Drug Effects Gastritis Isolation And Purification Leukocyte Medicinal Plant Metabolism Neutrophil Phytotherapy Simaroubaceae Stomach Mucosa Animal Anti-inflammatory Agents, Non-steroidal Cell Adhesion Cytokines Dinoprostone Disease Models, Animals Dose-response Relationship, Drug Gastric Mucosa Gastritis Indomethacin Leukocytes Male Mice Mice, Inbred C57bl Molecular Structure Neutrophils Phytotherapy Plant Extracts Plant Roots Plant Stems Plants, Medicinal Quassins Simaroubaceae
Acesso em linha:	https://repositorio.inpa.gov.br/handle/1/17680

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spelling	oai:repositorio:1-17680 Gastro-protective effects of isobrucein B, a quassinoid isolated from Picrolemma sprucei Manfredo Vieira, Silvio Silva, Rangel Leal Lemos, Henrique Paula Amorim, Rodrigo C.N. Silva, Ellen Cristina Costa Reinach, Peter Sol Cunha, Fernando Queiroz Pohlit, Adrian Martin Cunha, Thiago Mattar Cxcl1 Chemokine Interleukin-1beta Isobrucein B Nonsteroid Antiinflammatory Agent Prostaglandin E2 Prostaglandin Synthase Protective Agent Quassinoid Derivative Tumor Necrosis Factor-alpha Unclassified Drug Cytokine Indometacin Isobrucein B Nonsteroid Antiinflammatory Agent Plant Extract Prostaglandin E2 Quassinoid Derivative Adult Animals Experiment Animals Model Animals Tissue Capillary Wall Carbon Nuclear Magnetic Resonance Controlled Study Drug Mechanism Enzyme-linked Immunosorbent Assay Gastritis Leukocyte Adherence Leukocyte Migration Leukocyte Rolling Male Microcirculation Mouse Neutrophil Chemotaxis Nonhuman Pathophysiology Picrolemma sprucei Plant Root Plant Stem Priority Journal Prostaglandin Synthesis Protection Proton Nuclear Magnetic Resonance Simaroubaceae Stomach Injury Stomach Lesion Animals C57bl Mouse Cell Adhesion Chemical Structure Chemically Induced Chemistry Disease Model Dose Response Drug Effects Gastritis Isolation And Purification Leukocyte Medicinal Plant Metabolism Neutrophil Phytotherapy Simaroubaceae Stomach Mucosa Animal Anti-inflammatory Agents, Non-steroidal Cell Adhesion Cytokines Dinoprostone Disease Models, Animals Dose-response Relationship, Drug Gastric Mucosa Gastritis Indomethacin Leukocytes Male Mice Mice, Inbred C57bl Molecular Structure Neutrophils Phytotherapy Plant Extracts Plant Roots Plant Stems Plants, Medicinal Quassins Simaroubaceae Infusions 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. © 2014 Elsevier B.V. 2020-06-15T21:48:47Z 2020-06-15T21:48:47Z 2014 Artigo https://repositorio.inpa.gov.br/handle/1/17680 10.1016/j.fitote.2014.02.008 en Volume 95, Pags. 8-15 Restrito Fitoterapia
institution	Instituto Nacional de Pesquisas da Amazônia - Repositório Institucional
collection	INPA-RI
language	English
topic	Cxcl1 Chemokine Interleukin-1beta Isobrucein B Nonsteroid Antiinflammatory Agent Prostaglandin E2 Prostaglandin Synthase Protective Agent Quassinoid Derivative Tumor Necrosis Factor-alpha Unclassified Drug Cytokine Indometacin Isobrucein B Nonsteroid Antiinflammatory Agent Plant Extract Prostaglandin E2 Quassinoid Derivative Adult Animals Experiment Animals Model Animals Tissue Capillary Wall Carbon Nuclear Magnetic Resonance Controlled Study Drug Mechanism Enzyme-linked Immunosorbent Assay Gastritis Leukocyte Adherence Leukocyte Migration Leukocyte Rolling Male Microcirculation Mouse Neutrophil Chemotaxis Nonhuman Pathophysiology Picrolemma sprucei Plant Root Plant Stem Priority Journal Prostaglandin Synthesis Protection Proton Nuclear Magnetic Resonance Simaroubaceae Stomach Injury Stomach Lesion Animals C57bl Mouse Cell Adhesion Chemical Structure Chemically Induced Chemistry Disease Model Dose Response Drug Effects Gastritis Isolation And Purification Leukocyte Medicinal Plant Metabolism Neutrophil Phytotherapy Simaroubaceae Stomach Mucosa Animal Anti-inflammatory Agents, Non-steroidal Cell Adhesion Cytokines Dinoprostone Disease Models, Animals Dose-response Relationship, Drug Gastric Mucosa Gastritis Indomethacin Leukocytes Male Mice Mice, Inbred C57bl Molecular Structure Neutrophils Phytotherapy Plant Extracts Plant Roots Plant Stems Plants, Medicinal Quassins Simaroubaceae
spellingShingle	Cxcl1 Chemokine Interleukin-1beta Isobrucein B Nonsteroid Antiinflammatory Agent Prostaglandin E2 Prostaglandin Synthase Protective Agent Quassinoid Derivative Tumor Necrosis Factor-alpha Unclassified Drug Cytokine Indometacin Isobrucein B Nonsteroid Antiinflammatory Agent Plant Extract Prostaglandin E2 Quassinoid Derivative Adult Animals Experiment Animals Model Animals Tissue Capillary Wall Carbon Nuclear Magnetic Resonance Controlled Study Drug Mechanism Enzyme-linked Immunosorbent Assay Gastritis Leukocyte Adherence Leukocyte Migration Leukocyte Rolling Male Microcirculation Mouse Neutrophil Chemotaxis Nonhuman Pathophysiology Picrolemma sprucei Plant Root Plant Stem Priority Journal Prostaglandin Synthesis Protection Proton Nuclear Magnetic Resonance Simaroubaceae Stomach Injury Stomach Lesion Animals C57bl Mouse Cell Adhesion Chemical Structure Chemically Induced Chemistry Disease Model Dose Response Drug Effects Gastritis Isolation And Purification Leukocyte Medicinal Plant Metabolism Neutrophil Phytotherapy Simaroubaceae Stomach Mucosa Animal Anti-inflammatory Agents, Non-steroidal Cell Adhesion Cytokines Dinoprostone Disease Models, Animals Dose-response Relationship, Drug Gastric Mucosa Gastritis Indomethacin Leukocytes Male Mice Mice, Inbred C57bl Molecular Structure Neutrophils Phytotherapy Plant Extracts Plant Roots Plant Stems Plants, Medicinal Quassins Simaroubaceae Manfredo Vieira, Silvio Gastro-protective effects of isobrucein B, a quassinoid isolated from Picrolemma sprucei
topic_facet	Cxcl1 Chemokine Interleukin-1beta Isobrucein B Nonsteroid Antiinflammatory Agent Prostaglandin E2 Prostaglandin Synthase Protective Agent Quassinoid Derivative Tumor Necrosis Factor-alpha Unclassified Drug Cytokine Indometacin Isobrucein B Nonsteroid Antiinflammatory Agent Plant Extract Prostaglandin E2 Quassinoid Derivative Adult Animals Experiment Animals Model Animals Tissue Capillary Wall Carbon Nuclear Magnetic Resonance Controlled Study Drug Mechanism Enzyme-linked Immunosorbent Assay Gastritis Leukocyte Adherence Leukocyte Migration Leukocyte Rolling Male Microcirculation Mouse Neutrophil Chemotaxis Nonhuman Pathophysiology Picrolemma sprucei Plant Root Plant Stem Priority Journal Prostaglandin Synthesis Protection Proton Nuclear Magnetic Resonance Simaroubaceae Stomach Injury Stomach Lesion Animals C57bl Mouse Cell Adhesion Chemical Structure Chemically Induced Chemistry Disease Model Dose Response Drug Effects Gastritis Isolation And Purification Leukocyte Medicinal Plant Metabolism Neutrophil Phytotherapy Simaroubaceae Stomach Mucosa Animal Anti-inflammatory Agents, Non-steroidal Cell Adhesion Cytokines Dinoprostone Disease Models, Animals Dose-response Relationship, Drug Gastric Mucosa Gastritis Indomethacin Leukocytes Male Mice Mice, Inbred C57bl Molecular Structure Neutrophils Phytotherapy Plant Extracts Plant Roots Plant Stems Plants, Medicinal Quassins Simaroubaceae
description	Infusions 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. © 2014 Elsevier B.V.
format	Artigo
author	Manfredo Vieira, Silvio
author2	Silva, Rangel Leal Lemos, Henrique Paula Amorim, Rodrigo C.N. Silva, Ellen Cristina Costa Reinach, Peter Sol Cunha, Fernando Queiroz Pohlit, Adrian Martin Cunha, Thiago Mattar
author2Str	Silva, Rangel Leal Lemos, Henrique Paula Amorim, Rodrigo C.N. Silva, Ellen Cristina Costa Reinach, Peter Sol Cunha, Fernando Queiroz Pohlit, Adrian Martin Cunha, Thiago Mattar
title	Gastro-protective effects of isobrucein B, a quassinoid isolated from Picrolemma sprucei
title_short	Gastro-protective effects of isobrucein B, a quassinoid isolated from Picrolemma sprucei
title_full	Gastro-protective effects of isobrucein B, a quassinoid isolated from Picrolemma sprucei
title_fullStr	Gastro-protective effects of isobrucein B, a quassinoid isolated from Picrolemma sprucei
title_full_unstemmed	Gastro-protective effects of isobrucein B, a quassinoid isolated from Picrolemma sprucei
title_sort	gastro-protective effects of isobrucein b, a quassinoid isolated from picrolemma sprucei
publisher	Fitoterapia
publishDate	2020
url	https://repositorio.inpa.gov.br/handle/1/17680
_version_	1787144549911494656
score	11.675608

Gastro-protective effects of isobrucein B, a quassinoid isolated from Picrolemma sprucei

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