Your browser doesn't support javascript.
loading
Renoprotective effect of rosmarinic acid by inhibition of indoxyl sulfate-induced renal interstitial fibrosis via the NLRP3 inflammasome signaling.
Hung, Tung-Wei; Hsieh, Yi-Hsien; Lee, Hsiang-Lin; Ting, Yi-Hsuan; Lin, Chu-Liang; Chao, Wen-Wan.
Afiliación
  • Hung TW; School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Division of Nephrology, Department of Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
  • Hsieh YH; Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
  • Lee HL; School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Deptartment of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
  • Ting YH; Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
  • Lin CL; Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
  • Chao WW; Department of Nutrition and Health Sciences, Kainan University, Taoyuan 33857, Taiwan. Electronic address: wwchao@mail.knu.edu.tw.
Int Immunopharmacol ; 135: 112314, 2024 Jun 30.
Article en En | MEDLINE | ID: mdl-38788450
ABSTRACT
We previously reported that rosmarinic acid (RA) ameliorated renal fibrosis in a unilateral ureteral obstruction (UUO) murine model of chronic kidney disease. This study aimed to determine whether RA attenuates indoxyl sulfate (IS)-induced renal fibrosis by regulating the activation of the NLRP3 inflammasome/IL-1ß/Smad circuit. We discovered the NLRP3 inflammasome was activated in the IS treatment group and downregulated in the RA-treated group in a dose-dependent manner. Additionally, the downstream effectors of the NLRP3 inflammasome, cleaved-caspase-1 and cleaved-IL-1ß showed similar trends in different groups. Moreover, RA administration significantly decreased the ROS levels of reactive oxygen species in IS-treated cells. Our data showed that RA treatment significantly inhibited Smad-2/3 phosphorylation. Notably, the effects of RA on NLRP3 inflammasome/IL-1ß/Smad and fibrosis signaling were reversed by the siRNA-mediated knockdown of NLRP3 or caspase-1 in NRK-52E cells. In vivo, we demonstrated that expression levels of NLRP3, c-caspase-1, c-IL-1ß, collagen I, fibronectin and α-SMA, and TGF- ß 1 were downregulated after treatment of UUO mice with RA or RA + MCC950. Our findings suggested RA and MCC950 synergistically inhibited UUO-induced NLRP3 signaling activation, revealing their renoprotective properties and the potential for combinatory treatment of renal fibrosis and chronic kidney inflammation.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrosis / Transducción de Señal / Cinamatos / Depsidos / Inflamasomas / Proteína con Dominio Pirina 3 de la Familia NLR / Ácido Rosmarínico / Indicán / Riñón / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrosis / Transducción de Señal / Cinamatos / Depsidos / Inflamasomas / Proteína con Dominio Pirina 3 de la Familia NLR / Ácido Rosmarínico / Indicán / Riñón / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos