RESUMO
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.
Assuntos
Antibacterianos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Imunomodulação/efeitos dos fármacos , Pneumonia Estafilocócica/prevenção & controle , Polygonum/química , Substâncias Protetoras/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Líquido da Lavagem Broncoalveolar/química , Quimiocina CCL2/análise , Contagem de Colônia Microbiana , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Interleucina-6/análise , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos Endogâmicos C57BL , Pneumonia Estafilocócica/tratamento farmacológico , Pneumonia Estafilocócica/patologia , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análiseRESUMO
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.
Assuntos
Animais , Pneumonia Estafilocócica/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Substâncias Protetoras/farmacologia , Polygonum/química , Imunomodulação/efeitos dos fármacos , Antibacterianos/farmacologia , Pneumonia Estafilocócica/patologia , Pneumonia Estafilocócica/tratamento farmacológico , Fatores de Tempo , Ensaio de Imunoadsorção Enzimática , Líquido da Lavagem Broncoalveolar/química , Imuno-Histoquímica , Contagem de Colônia Microbiana , Reprodutibilidade dos Testes , Interleucina-6/análise , Fator de Necrose Tumoral alfa/análise , Resultado do Tratamento , Quimiocina CCL2/análise , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos Endogâmicos C57BLRESUMO
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.
Assuntos
Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Curcumina/análogos & derivados , Curcumina/farmacologia , Neuropatias Diabéticas/tratamento farmacológico , Canal de Cátion TRPA1/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/análise , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Cálcio/análise , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Neuropatias Diabéticas/metabolismo , Masculino , Microscopia de Fluorescência , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Estreptozocina , Canal de Cátion TRPA1/análise , Fatores de TempoRESUMO
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.
