Kirenol alleviates diabetic nephropathy via regulating TGF-ß/Smads and the NF-κB signal pathway.
Pharm Biol
; 60(1): 1690-1700, 2022 Dec.
Article
en En
| MEDLINE
| ID: mdl-36073930
ABSTRACT
CONTEXT Kirenol possesses anti-inflammatory, antifibrotic and anti-arthritic effects. However, its reno-protective effects against diabetic nephropathy (DN) have not been evaluated. OBJECTIVE:
This study explores the reno-protective effects of kirenol against DN and clarifies the potential mechanisms. MATERIALS ANDMETHODS:
The mesangial cells were treated with 20 µM kirenol and 10 ng/mL human recombinant TGF-ß1 or 30 mM glucose for 24 h. Then the cells were harvested to assay the expression of the target genes or proteins. Thirty C57BL/6J male mice were given high-fat diet with streptozotocin injection to induce diabetes and then were randomized into three groups (n = 10) vehicle administration (DM group), 2 mg/kg kirenol (DM + kirenol group) and 200 mg/kg metformin (Met group) for 3 months, orally. A healthy group (Con, n = 10) was included as the control.RESULTS:
Compared to the DM group, kirenol treatment decreased the phosphorylation of Smad2/3 and NF-κB (0.64- and 0.43-fold) as well as the accumulation of FN and Col IV (0.58- and 0.35-fold); moreover, the expression of IκBα was restored to normal level by kirenol treatment both in vivo and in vitro. After kirenol treatment, IL-6 expression was decreased 0.35- and 0.57-fold, and TNF-α expression was decreased 0.34- and 0.46-fold, in vitro and in vivo, respectively. Furthermore, kirenol alleviated the glomerular basement membrane thickness and foot process fusion. DISCUSSION ANDCONCLUSIONS:
Kirenol could alleviate DN by downregulating the TGF-ß/Smads and the NF-κB signal pathway. Our study provides a potential mechanism for the treatment of DN with kirenol.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Experimental
/
Nefropatías Diabéticas
Tipo de estudio:
Clinical_trials
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Pharm Biol
Año:
2022
Tipo del documento:
Article
País de afiliación:
China