RESUMEN
PURPOSE: To investigate the efficacy and mechanisms of root tuber of Polygonum ciliinerve (Nakai) ohwi (rPC) which has been used to treat bacterial infection in traditional Chinese medicine. METHODS: With the mouse model of Staphylococcus aureus (S. aureus) pneumonia, the phenotype of rPC treated mice, including body weight, mortality, lung slices and bacterial burden were evaluated. Furthermore, inflammatory factors in bronchoalveolar lavage (BAL) were determined by ELISA and the distribution of T cells in lung was assessed by immunofluorescence assay. RESULTS: rPC treatment could dose-dependently reduce weight loss and mortality in S. aureus-infected mice. Upon 10 mg/ml rPC treatment, S. aureus-infected mice showed about 8 grams increase in body weight (P<0.001) and 50% enhancement in mortality. The integrity of lung tissue and bacterial burden were also improved by rPC treatment. Moreover, rPC was found to modulate the immune response in infection. CONCLUSION: rPC has therapeutic potential for S. aureus infections and pneumonia with immunomodulatory functions.
Asunto(s)
Antibacterianos/farmacología , Medicamentos Herbarios Chinos/farmacología , Inmunomodulación/efectos de los fármacos , Neumonía Estafilocócica/prevención & control , Polygonum/química , Sustancias Protectoras/farmacología , Staphylococcus aureus/efectos de los fármacos , Animales , Líquido del Lavado Bronquioalveolar/química , Quimiocina CCL2/análisis , Recuento de Colonia Microbiana , Ensayo de Inmunoadsorción Enzimática , Inmunohistoquímica , Interleucina-6/análisis , Pulmón/efectos de los fármacos , Pulmón/patología , Ratones Endogámicos C57BL , Neumonía Estafilocócica/tratamiento farmacológico , Neumonía Estafilocócica/patología , Reproducibilidad de los Resultados , Factores de Tiempo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Abstract Purpose: To investigate the efficacy and mechanisms of root tuber of Polygonum ciliinerve (Nakai) ohwi (rPC) which has been used to treat bacterial infection in traditional Chinese medicine. Methods: With the mouse model of Staphylococcus aureus (S. aureus) pneumonia, the phenotype of rPC treated mice, including body weight, mortality, lung slices and bacterial burden were evaluated. Furthermore, inflammatory factors in bronchoalveolar lavage (BAL) were determined by ELISA and the distribution of T cells in lung was assessed by immunofluorescence assay. Results: rPC treatment could dose-dependently reduce weight loss and mortality in S. aureus-infected mice. Upon 10 mg/ml rPC treatment, S. aureus-infected mice showed about 8 grams increase in body weight (P<0.001) and 50% enhancement in mortality. The integrity of lung tissue and bacterial burden were also improved by rPC treatment. Moreover, rPC was found to modulate the immune response in infection. Conclusion: rPC has therapeutic potential for S. aureus infections and pneumonia with immunomodulatory functions.
Asunto(s)
Animales , Neumonía Estafilocócica/prevención & control , Staphylococcus aureus/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Sustancias Protectoras/farmacología , Polygonum/química , Inmunomodulación/efectos de los fármacos , Antibacterianos/farmacología , Neumonía Estafilocócica/patología , Neumonía Estafilocócica/tratamiento farmacológico , Factores de Tiempo , Ensayo de Inmunoadsorción Enzimática , Líquido del Lavado Bronquioalveolar/química , Inmunohistoquímica , Recuento de Colonia Microbiana , Reproducibilidad de los Resultados , Interleucina-6/análisis , Factor de Necrosis Tumoral alfa/análisis , Resultado del Tratamiento , Quimiocina CCL2/análisis , Pulmón/efectos de los fármacos , Pulmón/patología , Ratones Endogámicos C57BLRESUMEN
PURPOSE: To investigate the specific molecular mechanisms and effects of curcumin derivative J147 on diabetic peripheral neuropathy (DPN). METHODS: We constructed streptozotocin (STZ)-induced DPN rat models to detected mechanical withdrawal threshold (MWT) in vivo using Von Frey filaments. In vitro, we measured cell viability and apoptosis, adenosine 5'-monophosphate-activated protein kinase (AMPK) and transient receptor potential A1 (TRPA1) expression using MTT, flow cytometry, qRT-PCR and western blot. Then, TRPA1 expression level and calcium reaction level were assessed in agonist AICAR treated RSC96cells. RESULTS: The results showed that J147reduced MWT in vivo, increased the mRNA and protein level of AMPK, reduced TRPA1 expression and calcium reaction level in AITCR treated RSC96 cells, and had no obvious effect on cell viability and apoptosis. Besides, AMPK negative regulated TRPA1 expression in RSC96 cells. CONCLUSIONS: J147 could ameliorate DPN via negative regulation AMPK on TRPA1 in vivo and in vitro. A curcumin derivative J147might be a new therapeutic potential for the treatment of DPN.
Asunto(s)
Proteínas Quinasas Activadas por AMP/efectos de los fármacos , Curcumina/análogos & derivados , Curcumina/farmacología , Neuropatías Diabéticas/tratamiento farmacológico , Canal Catiónico TRPA1/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/análisis , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Calcio/análisis , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Neuropatías Diabéticas/metabolismo , Masculino , Microscopía Fluorescente , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Estreptozocina , Canal Catiónico TRPA1/análisis , Factores de TiempoRESUMEN
Abstract Purpose: To investigate the specific molecular mechanisms and effects of curcumin derivative J147 on diabetic peripheral neuropathy (DPN). Methods: We constructed streptozotocin (STZ)-induced DPN rat models to detected mechanical withdrawal threshold (MWT) in vivo using Von Frey filaments. In vitro, we measured cell viability and apoptosis, adenosine 5'-monophosphate-activated protein kinase (AMPK) and transient receptor potential A1 (TRPA1) expression using MTT, flow cytometry, qRT-PCR and western blot. Then, TRPA1 expression level and calcium reaction level were assessed in agonist AICAR treated RSC96cells. Results: The results showed that J147reduced MWT in vivo, increased the mRNA and protein level of AMPK, reduced TRPA1 expression and calcium reaction level in AITCR treated RSC96 cells, and had no obvious effect on cell viability and apoptosis. Besides, AMPK negative regulated TRPA1 expression in RSC96 cells. Conclusions: J147 could ameliorate DPN via negative regulation AMPK on TRPA1 in vivo and in vitro. A curcumin derivative J147might be a new therapeutic potential for the treatment of DPN.