RESUMO
Acanthopanacis Cortex (A.-C) with a long history of more than1000 years, has been used to treat rheumatism effectively. Nineteen diterpenoids have been isolated from A.-C, including six new compounds (1-6). Among them, compounds 7, 9-11, 13, and 17 were discovered from A.-C for the first time. The structures of 1-6 were determined by analyzing their NMR data and comparing their experimental and calculated electronic circular dichroism spectra. Moreover, the single-crystal X-ray diffraction data of 1, 2, 8, and 14 were provided. The anti-inflammatory activity of 1-5 and 7-18 on neutrophil elastase, cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2) has been studied in vitro, and the results showed that 15 had almost no inhibitory effects on COX-1 at 200 µM but a significant activity against COX-2 with an IC50 of 0.73 ± 0.006 µΜ. It indicated that compound 15 can provide valuable information for the design of selective COX-2 inhibitors.
Assuntos
Anti-Inflamatórios , Ciclo-Oxigenase 2 , Diterpenos , Elastase de Leucócito , Diterpenos/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/química , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/química , Ciclo-Oxigenase 2/metabolismo , Elastase de Leucócito/antagonistas & inibidores , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Ciclo-Oxigenase 1/metabolismo , Acanthaceae/química , Humanos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , ChinaRESUMO
PURPOSE: To explore the potential role and unclear molecular mechanisms of vaccarin in wound healing. METHODS: Rats' skin excision model to study the effects of vaccarin on wound healing in vivo . Hematoxylin and eosin staining was performed to evaluate Histopathologic characteristics. Immunohistochemistry was employed to assess the effects of vaccarin in accelerating angiogenesis. Western blot was used to evaluate relative protein expressed levels. RESULTS: Vaccarin could significantly promote wound healing and endothelial cells and fibroblasts proliferation in the wound site. Immunohistochemistry and Western blot studies showed that the nodal proteins and receptor (bFGFR) related to angiogenesis signaling pathway were activated, and the microvascular density in the wound site was markedly higher than that in the control group. CONCLUSIONS: The present study was the first to demonstrate that vaccarin is able to induce angiogenesis and accelerate wound healing in vivo by increasing expressions of p-Akt, p-Erk and p-bFGFR. This process is mediated by MAPK/ERK and PI3K/AKT signaling pathways.
Assuntos
Indutores da Angiogênese/farmacologia , Caryophyllaceae/química , Quinases de Proteína Quinase Ativadas por Mitógeno/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Western Blotting , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno/análise , Fosfatidilinositol 3-Quinases/análise , Extratos Vegetais/química , Ratos Sprague-Dawley , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/análise , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/efeitos dos fármacos , Reprodutibilidade dos Testes , Transdução de Sinais , Fatores de TempoRESUMO
Abstract Purpose To explore the potential role and unclear molecular mechanisms of vaccarin in wound healing. Methods Rats' skin excision model to study the effects of vaccarin on wound healing in vivo . Hematoxylin and eosin staining was performed to evaluate Histopathologic characteristics. Immunohistochemistry was employed to assess the effects of vaccarin in accelerating angiogenesis. Western blot was used to evaluate relative protein expressed levels. Results Vaccarin could significantly promote wound healing and endothelial cells and fibroblasts proliferation in the wound site. Immunohistochemistry and Western blot studies showed that the nodal proteins and receptor (bFGFR) related to angiogenesis signaling pathway were activated, and the microvascular density in the wound site was markedly higher than that in the control group. Conclusions The present study was the first to demonstrate that vaccarin is able to induce angiogenesis and accelerate wound healing in vivo by increasing expressions of p-Akt, p-Erk and p-bFGFR. This process is mediated by MAPK/ERK and PI3K/AKT signaling pathways.
Assuntos
Animais , Masculino , Cicatrização/efeitos dos fármacos , Extratos Vegetais/farmacologia , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Quinases de Proteína Quinase Ativadas por Mitógeno/efeitos dos fármacos , Caryophyllaceae/química , Indutores da Angiogênese/farmacologia , Fatores de Tempo , Imuno-Histoquímica , Extratos Vegetais/química , Transdução de Sinais , Western Blotting , Reprodutibilidade dos Testes , Ratos Sprague-Dawley , Fosfatidilinositol 3-Quinases/análise , Quinases de Proteína Quinase Ativadas por Mitógeno/análise , Células Endoteliais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/análise , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos dos fármacosRESUMO
Purpose To explore the potential role and unclear molecular mechanisms of vaccarin in wound healing. Methods Rats skin excision model to study the effects of vaccarin on wound healing in vivo . Hematoxylin and eosin staining was performed to evaluate Histopathologic characteristics. Immunohistochemistry was employed to assess the effects of vaccarin in accelerating angiogenesis. Western blot was used to evaluate relative protein expressed levels. Results Vaccarin could significantly promote wound healing and endothelial cells and fibroblasts proliferation in the wound site. Immunohistochemistry and Western blot studies showed that the nodal proteins and receptor (bFGFR) related to angiogenesis signaling pathway were activated, and the microvascular density in the wound site was markedly higher than that in the control group. Conclusions The present study was the first to demonstrate that vaccarin is able to induce angiogenesis and accelerate wound healing in vivo by increasing expressions of p-Akt, p-Erk and p-bFGFR. This process is mediated by MAPK/ERK and PI3K/AKT signaling pathways.(AU)