RESUMO
The present study aims to explore the anti-inflammatory potential activity of the hexane extract from branches (HEB) of Endlicheria paniculata (Lauraceae) and its main compound, methyldehydrodieugenol B, in the inflammatory response induced by a murine implant sponge model. HPLC-ESI/MS analysis of HEB led to the identification of six chemically related neolignans, with methyldehydrodieugenol B as the main compound. An in silico analysis of the pharmacokinetic parameters of the identified compounds suggested moderate solubility but good absorption and biodistribution in vivo. Thus, the treatment of mice with HEB using in vivo assays indicated that HEB promoted pro-inflammatory, antiangiogenic, and antifibrogenic effects, whereas treatment with methyldehydrodieugenol B caused anti-inflammatory, antifibrogenic, and antiangiogenic effects. The obtained results shown the therapeutic potential of HEB and methyldehydrodieugenol B in the treatment of pathologies associated with inflammation and angiogenesis, including chronic wounds.
Assuntos
Hexanos , Lauraceae , Camundongos , Animais , Distribuição Tecidual , Extratos Vegetais/farmacologia , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Lauraceae/química , Fatores de Transcrição Hélice-Alça-Hélice BásicosRESUMO
The present study reports the evaluation of hexane extract from Endlicheria paniculata and its main metabolite dehydrodieugenol B in the inflammatory response induced by a murine implant sponge model. As a result, a reduction in the inflammatory markers (myeloperoxidase and N-acetyl-ß-D-glucosaminidase) and number of mast cells were observed in comparison to the control group. All doses were also able to reduce angiogenic parameters evaluated in fibrovascular tissue. In implants treated with dehydrodieugenol B a reduction in total collagen deposition and types I and III collagen fibers were observed, while an increased in total collagen deposition and types I and III collagen fibers were observed in the treatment with hexane extract. Docking studies into cyclooxygenase-2 active site revealed that the dehydrodieugenol B had binding modes and energies comparable with celecoxib, diclofenac and ibuprofen. Therefore, dehydrodieugenol B was able to alter key components of chronic inflammation, resulting in a reduced inflammatory response and also presenting antifibrogenic and antiangiogenic effects. However, treatment with hexane extract resulted in a reduced inflammatory response with antiangiogenic effects, but caused fibrogenic effects.
Assuntos
Anisóis/farmacologia , Anti-Inflamatórios/farmacologia , Antifibrinolíticos/farmacologia , Lauraceae/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Inibidores da Angiogênese/farmacologia , Animais , Anisóis/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Antifibrinolíticos/isolamento & purificação , Brasil , Colágeno/metabolismo , Hexanos , Inflamação/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Folhas de Planta/químicaRESUMO
BACKGROUND: Peritoneal adhesions are nonanatomical connections that bind organs to the abdominal wall or among them. They arise after peritoneal injury, which triggers an inflammatory response followed by a healing process that leads to fibrotic tissue formation. Mesenchymal stem cells and their secretion products, also referred to as acellular derivatives (ACDs), have anti-inflammatory, fibrinolytic, and antifibrogenic properties. The aim of this study was to determine the effect of intraoperative administration of ACD on the appearance, severity, and progression of peritoneal adhesions, in an animal model. MATERIALS AND METHODS: Cecal erosions were mechanically induced in adult mice. Before closure, the vehicle, ACD, or Seprafilm was administered. Seven days later, the presence and grade of peritoneal adhesions were assessed macroscopically. One, 3, and 7 d after intervention, molecular and cellular markers of inflammation, fibrinolysis, and fibrogenesis were evaluated both locally and systemically. RESULTS: ACDs avoided the appearance of clinically relevant peritoneal adhesions. The vehicle had no effect, and Seprafilm reduced them inconsistently. The antiadhesive effect of ACD was associated with an early reduction of proinflammatory cytokine (tumor necrosis factor-alpha and interferon-gamma) secretion and leukocyte (polymorphonuclears, mononuclears, and macrophages) infiltration. High levels of D-dimer, low fibrin deposits, low myofibroblasts infiltration, and less fibrosis were also observed. CONCLUSIONS: ACD administered at the end of abdominal surgeries prevents the formation of peritoneal adhesions due to the modulation of inflammatory, fibrinolytic, and fibrogenic processes.