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Costunolide Inhibits Chronic Kidney Disease Development by Attenuating IKKß/NF-κB Pathway.
Zhao, Yang; Wang, Yi-Han; Tu, Wei-Chao; Wang, Da-Wei; Lu, Mu-Jun; Shao, Yuan.
Afiliación
  • Zhao Y; Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai, 201800, People's Republic of China.
  • Wang YH; Department of Urology, Sixth People's Hospital South Campus Affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China.
  • Tu WC; Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai, 201800, People's Republic of China.
  • Wang DW; Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai, 201800, People's Republic of China.
  • Lu MJ; Department of Urology and Andrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
  • Shao Y; Shanghai Institute of Andrology, Shanghai, People's Republic of China.
Drug Des Devel Ther ; 18: 2693-2712, 2024.
Article en En | MEDLINE | ID: mdl-38974121
ABSTRACT

Background:

Chronic kidney disease (CKD) is a significant worldwide health concern that leads to high mortality rates. The bioactive substance costunolide (CTD) has demonstrated several pharmacological effects and holds promise as a CKD treatment. This study aims to investigate the impact of CTD on CKD and delve into its mechanisms of action.

Methods:

Unilateral ureteral obstruction (UUO) methods and renal fibrosis mice models were created. Various concentrations of CTD were injected into UUO mice models to investigate the therapeutic effects of CTD on renal fibrosis of mice. Then, renal morphology, pathological changes, and the expression of genes related to fibrosis, inflammation and ferroptosis were analysed. RNA sequencing was utilized to identify the main biological processes and pathways involved in renal injury. Finally, both overexpression and inhibition of IKKß were studied to examine their respective effects on fibrosis and inflammation in both in vitro and in vivo models.

Results:

CTD treatment was found to significantly alleviate fibrosis, inflammation and ferroptosis in UUO-induced renal fibrosis mice models. The results of RNA sequencing suggested that the IKKß acted as key regulatory factor in renal injury and the expression of IKKß was increased in vitro and in vivo renal fibrosis model. Functionally, down-regulated IKKß expression inhibits ferroptosis, inflammatory cytokine production and collagen deposition. Conversely, IKKß overexpression exacerbates progressive renal fibrosis. Mechanistically, CTD alleviated renal fibrosis and inflammation by inhibiting the expression of IKKß and attenuating IKKß/NF-κB pathway.

Conclusion:

This study demonstrates that CTD could mitigate renal fibrosis, ferroptosis and inflammation in CKD by modulating the IKKß/NF-κB pathway, which indicates targeting IKKß has an enormous potential for treating CKD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sesquiterpenos / Insuficiencia Renal Crónica Límite: Animals / Humans / Male Idioma: En Revista: Drug Des Devel Ther Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article Pais de publicación: Nueva Zelanda
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: Sesquiterpenos / Insuficiencia Renal Crónica Límite: Animals / Humans / Male Idioma: En Revista: Drug Des Devel Ther Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article Pais de publicación: Nueva Zelanda