RESUMO
Microglial activation plays an important role in the development and progression of various neurological disorders such as cerebral ischemia, multiple sclerosis, and Alzheimer's disease. Thus, controlling microglial activation can serve as a promising therapeutic strategy for such brain diseases. In the present study, we showed that kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus, inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-alpha expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-inflammatory cytokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-kappaB and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with upregulation of anti-inflammatory hemeoxygenase-1 (HO-1) expression. Based on the previous reports that JNK pathway is largely involved in iNOS and proinflammatory cytokine gene expression via modulating NF-kappaB/AP-1 and ROS, our data collectively suggest that inhibition of JNK pathway plays a key role in anti-inflammatory effects of kalopanaxsaponin A in LPS-stimulated microglia.
Assuntos
Doença de Alzheimer , Encefalopatias , Isquemia Encefálica , Ciclo-Oxigenase 2 , DNA , Expressão Gênica , Interleucinas , Kalopanax , Sistema de Sinalização das MAP Quinases , Microglia , Esclerose Múltipla , Doenças do Sistema Nervoso , NF-kappa B , Óxido Nítrico Sintase Tipo II , Fosforilação , Fosfotransferases , Saponinas , Fator de Transcrição AP-1 , Fator de Necrose Tumoral alfa , Regulação para CimaRESUMO
BACKGROUND: T. vaginalis is a pathogenic protozoa infecting genitourinary tract. Metronidazole is a drug of choice to treat T. vaginalis infection. However, because of appearance of metronidazole- resistant T. vaginalis, it is needed to develop an alternative drug. So, we evaluated the effects of various concentration of kalopanaxsaponin A against T. vaginalis. METHODS: The antiprotozoal effect of kalopanaxsaponin A on the growth and fine structure of T. vaginalis was examined by using trypan blue exclusion assay and electron microscopy. RESULTS: The viability test showed markedly decreased number of T. vaginalis, treated with increasing concentration of kalopanaxsaponin A. We evaluated the electron microscopic findings for antiprotozoan effects against T. vaginalis. SEM showed that in T. vaginalis treated with 4 microgram/mL for 1 hour, axostyle was shrinked and flagella began to disappear. With gradual increase of the concentration of kalopanaxsaponin A, destruction of cell membrane was getting more severe, and degenerative change was observed in T. vaginalis treated with 8 microgram/mL for 2 hours. TEM showed that in T. vaginalis treated with 4 microgram/mL for 2 hours, the vacuoles in cytoplasm were larger and hydrogenosomes were smaller than those in control group. The number of vacuole was increased, the nucleus was destroyed, the number of polyribosome and free ribosome was also decreased in trichomonads treated with kalopanaxsaponin A (8 microgram/mL), which indicated the occurrence of degenerative changes. CONCLUSION: These results indicated that kalopanaxsaponin A had the antiprotozoal effect on T. vaginalis by inhibition of cell multiplication as well as an impairment of protein synthesis.
Assuntos
Membrana Celular , Proliferação de Células , Citoplasma , Flagelos , Metronidazol , Microscopia Eletrônica , Polirribossomos , Ribossomos , Trichomonas vaginalis , Trichomonas , Azul Tripano , VacúolosRESUMO
BACKGROUND: T. vaginalis is a pathogenic protozoa infecting genitourinary tract. Metronidazole is a drug of choice to treat T. vaginalis infection. However, because of appearance of metronidazole- resistant T. vaginalis, it is needed to develop an alternative drug. So, we evaluated the effects of various concentration of kalopanaxsaponin A against T. vaginalis. METHODS: The antiprotozoal effect of kalopanaxsaponin A on the growth and fine structure of T. vaginalis was examined by using trypan blue exclusion assay and electron microscopy. RESULTS: The viability test showed markedly decreased number of T. vaginalis, treated with increasing concentration of kalopanaxsaponin A. We evaluated the electron microscopic findings for antiprotozoan effects against T. vaginalis. SEM showed that in T. vaginalis treated with 4 microgram/mL for 1 hour, axostyle was shrinked and flagella began to disappear. With gradual increase of the concentration of kalopanaxsaponin A, destruction of cell membrane was getting more severe, and degenerative change was observed in T. vaginalis treated with 8 microgram/mL for 2 hours. TEM showed that in T. vaginalis treated with 4 microgram/mL for 2 hours, the vacuoles in cytoplasm were larger and hydrogenosomes were smaller than those in control group. The number of vacuole was increased, the nucleus was destroyed, the number of polyribosome and free ribosome was also decreased in trichomonads treated with kalopanaxsaponin A (8 microgram/mL), which indicated the occurrence of degenerative changes. CONCLUSION: These results indicated that kalopanaxsaponin A had the antiprotozoal effect on T. vaginalis by inhibition of cell multiplication as well as an impairment of protein synthesis.