RESUMO
Tea (Camellia sinensis) is a beverage beneficial to health and is also a source for extracting bioactive components such as theanine, tea polyphenols (TPP) and tea polysaccharides (TPS). TPS is a group of heteropolysaccharides bound with proteins. There is evidence showing that TPS not only improves immunity but also has various bioactivities, such as antioxidant, antitumor, antihyperglycemia, and anti-inflammation. However, inconsistent results concerning chemical composition and bioactivity of TPS have been published in recent years. The advances in chemical composition and bioactivities of TPS are reviewed in the present paper. The inconsistent and controversial results regarding composition and bioactivities of TPS are also discussed.
Assuntos
Polissacarídeos/química , Polissacarídeos/farmacologia , Chá/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Disponibilidade Biológica , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Estrutura Molecular , Polissacarídeos/farmacocinéticaRESUMO
The present study aimed to determine the plausible functional role of chemokine (CXC motif) ligand 12 (CXCL12/chemokine (CXC motif) receptor 4 (CXCR4) in inflammatory corneal hemangiogenesis and lymphangiogenesis in vivo. Corneal hemangiogenesis and lymphangiogenesis were induced by placing an 110 nylon suture in an intrastromal position. The expression levels of the vascular endothelial growth factor (VEGF) family, CXCL12 and CXCR4 in the corneas were investigated in the corneas using reverse transcriptionquantitative polymerase chain reaction and immunohistochemistry. Corneal hemangiogenic and lymphangiogenic responses were assessed by immunofluorescence using specific antibodies against cluster of differentiation 31 and lymphatic vessel endothelial hyaluronan receptor1. Subconjunctival injection of AMD3100 to the sutured corneas was also performed. CXCL12/CXCR4 mRNA and protein expression levels increased markedly in sutureinduced corneal neovascularization (CNV) and decreased with AMD3100 treatment. Hemangiogenesis and lymphangiogenesis were captured in images using immunofluorescence and were shown to be markedly increased with suture placement and reduced with AMD3100 treatment. VEGFA/VEGFR1 and VEGFC/VEGFR3 mRNA expression levels were upregulated in the suture placement and control groups, whereas the expression levels of all the factors were downregulated in the AMD3100 treatment group. The results from the present study demonstrated that CXCL12/CXCR4 interactions regulate hemangiogenesis and lymphangiogenesis in sutureinduced CNV. AMD3100 may be a novel therapeutic target for the prevention of blindness.
Assuntos
Quimiocina CXCL12/metabolismo , Neovascularização da Córnea/metabolismo , Neovascularização da Córnea/patologia , Receptores CXCR4/metabolismo , Animais , Quimiocina CXCL12/genética , Neovascularização da Córnea/etiologia , Modelos Animais de Doenças , Expressão Gênica , Linfangiogênese/genética , Camundongos , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Receptores CXCR4/genética , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
PURPOSE: To investigate the potential inhibitory effects of RNA interference-mediated knockdown of neuropilin-2 (NP2) on inflammation-induced corneal hemangiogenesis and lymphangiogenesis, and whether selective inhibition of lymphangiogenesis on vascularized recipient beds before transplantation improves the graft survival. METHODS: Mouse lymphatic endothelial cells were transfected with the plasmid expressing artificial microRNA (amiRNA) against mouse NP2, and the down-regulation of VEGF-C-induced NP2 expression by NP2 amiRNA was evaluated by real-time PCR and western blot assays. Next, NP2 amiRNA or negative control amiRNA was injected intrastromally into BALB/c mouse model of suture-induced corneal neovascularization three days after surgery. Corneas were harvested 1 week after suture placement and the formation of lymphatic and blood vessels as well as the recruitment of macrophage was evaluated by immunohistochemical staining. The neovascularized graft beds treated by NP2 amiRNA or control then served as recipients of orthotopic corneal transplants, and age-matched C57BL/6 donors were used. Corneal allografts were examined twice a week for 8 weeks, and graft clarity was quantified by means of an opacity score. RESULTS: VEGF-C-induced NP2 expression at both mRNA and protein levels was significantly suppressed by NP2 amiRNA in mouse lymphatic endothelial cells. Intrastromal administration of NP2 amiRNA reduced corneal lymphangiogenesis by 45% versus control (p=0.015), but corneal hemangiogenesis (p=0.815) and the recruitment of CD11 antigen-like family member B (CD11b)-positive macrophage (p=0.589) were unchanged. Kaplan-Meier survival analysis revealed a better graft survival rate in the vascularized recipient beds pre-treated by NP2 amiRNA in comparison to controls (p=0.014). CONCLUSIONS: Knockdown of NP2 improves corneal graft survival by selectively inhibiting lymphangiogenesis in vascularized beds before transplantation. Thus our results open new treatment options for transplant rejection and other lymphatic disorders.