Isorhamnetin ameliorates cisplatin-induced acute kidney injury in mice by activating SLPI-mediated anti-inflammatory effect in macrophage.
Immunopharmacol Immunotoxicol
; 46(3): 319-329, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38466121
ABSTRACT
OBJECTIVE:
Isorhamnetin (IH) has been reported to have significant anti-inflammatory effects in various diseases, but its role and mechanism in AKI remain unclear. This study aimed to explore the potential role and mechanism of isorhamnetin in inhibiting macrophage related inflammation and improving AKI injury.METHODS:
We established an AKI mouse model by intraperitoneal injection of cisplatin in vivo, and constructed an inflammatory cell model by stimulating RAW264.7 cells with LPS. Creatinine and urea nitrogen were measured to evaluate the changes of renal function in AKI mice. The changes of renal pathological structure were observed by H&E staining. The inflammatory factor-related proteins and RNA expression levels were detected by Western blot and real time PCR.RESULTS:
Isorhamnetin protected the kidney from cisplatin induced AKI and significantly inhibited the mRNA and protein levels of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) both in AKI kidney and LPS-stimulated RAW264.7 cells. Interestingly, the data also demonstrated that isorhamnetin significantly upregulated the expression of secretory leukocyte peptidase inhibitor (SLPI), an anti-inflammatory factor, in AKI kidney and LPS-stimulated macrophages, as well as inhibited the M1 macrophage and activated M2 macrophage in vitro. Blocking of SLPI by siRNA activated Mincle-associated inflammatory signaling in macrophages, and the inhibitory effect of isorhamnetin on inflammation was significantly attenuated.CONCLUSION:
Isorhamnetin inhibits macrophage inflammation and protects kidney in AKI may be related to downregulating Mincle/Syk/NF-κB-maintained macrophage phenotype by activating SLPI.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quercetina
/
Cisplatino
/
Injúria Renal Aguda
/
Macrófagos
/
Anti-Inflamatórios
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article