RESUMO
Diabetic foot ulcer is closely associated with peripheral vascular disease. Enhancement of tissue oxidative stress, reduction of nitric oxide (NO) and angiogenic growth factors, and abnormal matrix metalloproteinase (MMP) activity are pathophysiological factors in post-ischemic neovascularization and diabetic wound healing. Our previous study demonstrated that the Chinese 2-herb formula, NF3, showed significant wound healing effects on diabetic foot ulcer rats. A novel rat diabetic foot ulcer with hindlimb ischemia model was established in order to strengthen our claims on the diabetic wound healing and post-ischemic neovascularization effects of NF3. Our results demonstrate that NF3 can significantly reduce the wound area of the diabetic foot ulcer rat with hindlimb ischemia by 21.6% (p<0.05) compared with the control group. In addition, flow cytometric analysis revealed that NF3 could boost circulating EPC levels for local wound vessel incorporation. Immunohistochemical analysis showed that NF3 could significantly augment blood vessel density, VEGF and eNOS expression, and attenuate tissue oxidative stress of ischemic muscles (p<0.001). NF3 significantly stimulated MMP activity involved in angiogenesis. Our study shows, for the first time, the beneficial effects of NF3 in wound healing and post-ischemic neovascularization in diabetes.
Assuntos
Indutores da Angiogênese/uso terapêutico , Pé Diabético/tratamento farmacológico , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Neovascularização Fisiológica/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Pé Diabético/etiologia , Pé Diabético/metabolismo , Pé Diabético/patologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Feminino , Membro Posterior , Isquemia/fisiopatologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Óxido Nítrico Sintase Tipo III/química , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/agonistas , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
To study the hypoglycemic mechanisms of a polysaccharide-rich extract of Radix Ophiopogonis, the influences of the extract on activity of NIT-1 insulinoma cells damaged by streptozotocin (STZ), activity of α-glucosidase, glucose absorption into intestinal brush border membrane vesicles, gluconeogenesis by H4IIE hepatoma cells and glucose uptake by 3T3-L1 adipocytes were investigated. The results show that the extract improved the activity of NIT-1 cells damaged by STZ, inhibited glucose absorption into intestinal brush border membrane vesicles and reduced the activity of α-glucosidase. However, gluconeogenesis in H4IIE cells and glucose uptake in 3T3-L1 adipocytes did not change significantly in the presence of the extract. These results suggest that the hypoglycemic mechanisms of the polysaccharide-rich extract of Radix Ophiopogonis are caused by protection in pancreatic islet cells and the inhibition of carbohydrate digestion and absorption. This is possibly the first report on the underlying mechanisms responsible for the antidiabetic effect of Radix Ophiopogonis.
Assuntos
Metabolismo dos Carboidratos/efeitos dos fármacos , Glucose/metabolismo , Hipoglicemiantes/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Liliaceae/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Gluconeogênese/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases , Hipoglicemiantes/uso terapêutico , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Insulinoma , Mucosa Intestinal/efeitos dos fármacos , Camundongos , Microvilosidades/efeitos dos fármacos , Neoplasias Pancreáticas , Fitoterapia , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Polissacarídeos/uso terapêutico , Coelhos , RatosRESUMO
Bioassay-guided phytochemical study of Androsace umbellata led to the successful isolation of saxifragifolin B (SB) for the first time. The anti-tumor effect of SB was firstly reported that it was shown to have potent cytotoxicity on human hepatoma HepG2 cells with IC50 value of 11.9 microM at 24 h. Mechanistic studies were conducted, the accumulation of sub-G1 population and the externalization of phosphatidylserine suggested that SB exerted its cytotoxic effect by induction of programmed cell death, which was confirmed by activation of PARP and caspase-3. Furthermore, SB-induced apoptosis on HepG2 cells was mediated by activation of caspase-8 and -9, mitochondrial membrane potential (Deltapsim) collapse and the leakage of cytochrome c. In summary, this study provided evidence that SB isolated from A. umbellata could induce apoptosis on human hepatoma HepG2 cells and described the molecular mechanism. Our finding revealed the potential of SB as new chemotherapeutic agent for human hepatoma.