A curcumin derivative J147 ameliorates diabetic peripheral neuropathy in streptozotocin (STZ)-induced DPN rat models through negative regulation AMPK on TRPA1
Acta cir. bras; 33 (6), 2018
Publication year: 2018
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.
Proteínas Quinasas Activadas por AMP/análisis, Proteínas Quinasas Activadas por AMP/efectos de los fármacos, Apoptosis/efectos de los fármacos, Western Blotting, Calcio/análisis, Supervivencia Celular/efectos de los fármacos, Células Cultivadas, Curcumina/análogos & derivados, Curcumina/farmacología, Diabetes Mellitus Experimental/complicaciones, Diabetes Mellitus Experimental/metabolismo, Neuropatías Diabéticas/tratamiento farmacológico, Neuropatías Diabéticas/metabolismo, Microscopía Fluorescente, Reacción en Cadena en Tiempo Real de la Polimerasa, Reproducibilidad de los Resultados, Estreptozocina, Canal Catiónico TRPA1/análisis, Canal Catiónico TRPA1/efectos de los fármacos, Factores de Tiempo